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Sample records for rat pups exposed

  1. Selenium dietary supplementation as a mechanism to restore hepatic selenoprotein regulation in rat pups exposed to alcohol.

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    Jotty, Karick; Ojeda, M Luisa; Nogales, Fátima; Murillo, M Luisa; Carreras, Olimpia

    2013-11-01

    Ethanol exposure during gestation and lactation decreases selenium (Se) intake, disrupting body Se balance and inducing oxidative stress in rat offspring. Selenium-supplemented diet (0.5 ppm) was administered to ethanol-exposed (20% v/v) dams during gestation and lactation. When the dams' pups were 21 days old, the pups' levels of the main hepatic selenoproteins glutathione peroxidase (GPx1 and GPx4) and selenoprotein P (SelP) were measured. The pups were divided into control (C), alcohol (A), control-selenium (CS), and alcohol-selenium (AS) groups. The purpose was to evaluate the effect of the selenium-supplemented diet on the levels of Se deposits present in the livers of their pups. Alcohol decreases hepatic Se deposits, GPx activity, and GPx1 expression; alcohol increases GPx4 and SelP expression. Se was measured by furnace graphite atomic absorption spectrometry, the antioxidant activity of GPx and concentration of hepatic phospholipids (PL) were determined by spectrophotometry, and the selenoprotein expressions were detected by Western blotting. Selenite treatment prevented alcohol's effects of diminishing the Se deposits, GPx activity, and GPx1 expression, while maintaining the high levels of the expression of GPx4 and SelP. These results suggest that depletion of hepatic Se levels in rat pups, caused by ethanol exposure to their dams, affects the synthesis of the 3 main hepatic selenoproteins in different ways, which is related to a decrease in GPx activity and PL concentration, and an increase in serum Se levels. Selenium supplementation to the dams increased the expression of GPx1, GPx4, and SelP in their pups.

  2. Cohabitation with a sterile male facilitates the development of retrieval behavior in nulliparous female rats exposed to pups.

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    Albert, D J; Jonik, R H; Tanco, S A; Walsh, M L

    1992-10-01

    Female rats were housed with a sterile male or another female. After 3 weeks, half of the females that had been housed with a female were rehoused with an intact male. At the end of 6 weeks female or sterile male cagemates were removed. Intact male cagemates and pups were removed 3 to 12 h following parturition. All females were tested for retrieval of three unfamiliar pups placed in their cage on the day following removal of their cagemate. Three unfamiliar pups were placed with each female and the female's behavior observed for 10 min. Observations were made in this way for 13 days or until the female retrieved all three pups within the 10-min interval. Pups were left with the female on days they were not retrieved. Females housed with a sterile male reached criterion for pup retrieval in 2.9 days, significantly fewer days than were required for females housed with another female (6.6 days) but significantly more than were required for a postpartum female (0.8 days). By demonstrating that cohabitation with a male fosters the development of retrieval, these results support evidence from the study of aggressive behavior that pseudopregnancy facilitates the development of behaviors associated with pregnancy and lactation.

  3. Attachment in rat pups, an experimental approach

    NARCIS (Netherlands)

    Gispen, W.H.; Sigling, H.; Engeland, H. van; Spruijt, B.M.

    1998-01-01

    John Bowlby's attachment theory states that attachment behavior has been strengthened throughout evolution as a consequence of its adaptive value. We investigated the presence of attachment-like behavior in rat pups, by offering a choice between the home nest and a same aged other nest. Rat pups sho

  4. Attachment in rat pups, an experimental approach

    NARCIS (Netherlands)

    Gispen, W.H.; Sigling, H.; Engeland, H. van; Spruijt, B.M.

    1998-01-01

    John Bowlby's attachment theory states that attachment behavior has been strengthened throughout evolution as a consequence of its adaptive value. We investigated the presence of attachment-like behavior in rat pups, by offering a choice between the home nest and a same aged other nest. Rat pups

  5. Exposure to pups influences the strength of maternal motivation in virgin female rats

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    Seip, Katharine M.; Morrell, Joan I.

    2008-01-01

    Following repeated exposure to foster pups, virgin female rats acquire and eventually express a full spectrum of maternal caretaking behaviors directed toward pups. Though these behaviors are vigorous, these females are reportedly less motivated to seek out and interact with pups (i.e. maternally motivated) than parturient females during early postpartum. The present study systematically assesses how the length of pup-exposure and nature of interactions between the female-pup dyad affect maternal motivation in the virgin female rat. Virgin females were exposed to young pups consistently (24 h/day) across a prolonged period (21 days), briefly (1 h/day) across a relatively brief period (7 days), or distally (pups inaccessible in mesh bag). During final pup-exposure days, females were conditioned and tested for their preference for a pup-associated chamber (e.g. maternal motivation) using conditioned place preference. Early postpartum females provided a comparison group. Fully maternal behavior only emerged in females given prolonged pup-exposure; this behavior improved significantly over time and was maximally expressed for a duration equivalent to early postpartum. Females given brief pup-exposure expressed only emergent maternal behaviors initiated by pups; distal pup-exposure evoked pup-avoidance. Virgin females given prolonged or brief pup-exposure expressed substantial pup-associated chamber preference, with more females preferring the pup-associated chamber following longer pup-exposures in a subtle stepwise relationship. Maternal motivation was strikingly similar in prolonged pup-exposure virgin and early postpartum females. Females given distal pup-exposure completely lacked maternal motivation. Maternal behavior did not predict chamber preference. Results suggest that pup-exposure, regardless of length, is sufficient to support strong maternal motivation, whereas parity is not required. PMID:18817796

  6. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

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    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  7. Pup age and aggressive behavior in lactating rats

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    Giovenardi M.

    2000-01-01

    Full Text Available High levels of aggressive behaviors against intruders in the nest area are displayed by female rats during the first 10 days after delivery, declining thereafter to very low levels, even though lactation continues. Cross-fostering experiments were undertaken to test the hypothesis that pup age may affect aggression in lactating rats. The behavior of females on the 8th day after delivery when raising fostered 8-day-old pups was compared to that of females on the 8th postpartum day raising older pups (18 days old for the last 5 days, and females on the 18th day after delivery raising fostered 18-day-old pups were compared to females in the same postpartum period nursing younger pups (8 days of age at the time of the maternal aggression test for 5 days. Pup retrieval activity and plasma prolactin level were also analyzed. Females on the 8th postpartum day nursing 18-day-old pups were less aggressive than females in the same postpartum period, but with 8-day-old pups. Likewise, females on the 18th postpartum day nursing younger pups were more aggressive and presented higher levels of prolactin than females nursing older pups. Thus, pup development can alter the natural decline of maternal aggressive behavior.

  8. Developmental vitamin D (DVD) deficiency alters pup-retrieval but not isolation-induced pup ultrasonic vocalizations in the rat.

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    Burne, Thomas H J; O'Loan, Jonathan; Splatt, Karisha; Alexander, Suzanne; McGrath, John J; Eyles, Darryl W

    2011-02-01

    Evidence from animal experiments now demonstrates that prenatal vitamin D levels influence brain development. The aims of this study were to examine isolation-induced pup ultrasonic vocalizations and maternal-infant interactions using a pup-retrieval test in developmental vitamin D (DVD) deficient and control rats. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. In two separate experiments we recorded ultrasonic vocalizations at 46KHz in isolated pups and we performed a pup-retrieval test on the day of birth. There was no significant effect of maternal diet on the calling rate of isolation-induced ultrasonic vocalizations by pups. We found that DVD-deficient dams retrieved their pups sooner than control dams and engaged in more pup directed activities (sniffing and carrying pups) and had a longer latency for self-grooming and rearing than control dams. We also assessed vitamin D related measures from a terminal blood sample immediately after the pup-retrieval test and found that DVD-deficient dams and pups had significantly lower levels of 25 OH D₃, 1,25 (OH)₂D₃ and phosphate, elevated levels of parathyroid hormone (PTH) but there was no significant effect of maternal diet on calcium levels. We speculate that the altered maternal-pup interactions identified in the DVD model may impact on early periods of brain development and behaviour.

  9. Developmental toxic effects in suckling pups of rats from dams treated with betamethasone

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    M. K. Shindala

    2009-01-01

    Full Text Available Suckling pups of rats from dams treated with betamethasone 0.3, 0.6, 1.2 mg/kg, i.p. given once daily for 10 consecutive days (first nursing period demonstrated in a dose – dependent manner significant decreased (P<0.05 the percentage of survival of the pups to weaning, body weight, index of development, whereas brain, heart, kindey, lung,liver / body weight ratio significantly increased (P<0.05 as well as delays in physical maturation (ear opening, fur development, tooth eruption, eye opening in the pups. Swimming scores on postnatal day 9, 13, 15, 17, 20 was significantly decreased (P<0.05 in offspring from mothers treated with betamethasone 1.2 mg/kg, i.p. In conclusion, the results suggest that betamethasone induced developmental toxic effects in suckling pups exposed to its through the milk.

  10. Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

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    Feng Jun-Tao

    2012-11-01

    Full Text Available Abstract Background Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established. Methods In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams. Results Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic dams. In pups exposed to nerve growth factor (NGF in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels. Conclusions Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process.

  11. Isolation of cardiac myocytes and fibroblasts from neonatal rat pups.

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    Golden, Honey B; Gollapudi, Deepika; Gerilechaogetu, Fnu; Li, Jieli; Cristales, Ricardo J; Peng, Xu; Dostal, David E

    2012-01-01

    Neonatal rat ventricular myocytes (NRVM) and fibroblasts (FBs) serve as in vitro models for studying fundamental mechanisms underlying cardiac pathologies, as well as identifying potential therapeutic targets. Both cell types are relatively easy to culture as monolayers and can be manipulated using molecular and pharmacological tools. Because NRVM cease to proliferate after birth, and FBs undergo phenotypic changes and senescence after a few passages in tissue culture, primary cultures of both cell types are required for experiments. Below we describe methods that provide good cell yield and viability of primary cultures of NRVM and FBs from 0 to 3-day-old neonatal rat pups.

  12. Perinatal thiamine deficiency-induced spontaneous abortion and pup-killing responses in rat dams.

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    Bâ, Abdoulaye

    2013-03-01

    The current study attempts to determine whether thiamine (B1 vitamin) deficiency and chronic alcohol-related thiamine-deficient (TD) status, disturb maternal behavior towards pups. During gestation and lactation, Wistar rat dams were exposed to the following treatments: (i) prenatal TD dams; (ii) perinatal TD dams; (iii) postnatal TD dams; (iv) 12% alcohol/water drinking mothers; (v) ad libitum control dams. Pair-feeding treatments controlled malnutrition related to thiamine deficiency; (vi) prenatal pair-fed (PF) dams; (vii) perinatal PF dams; (viii) postnatal PF dams and included also the control of alcohol consummation: (ix) PF saccharose dams. Dams were observed for gestation outcome and for apparent disorders of the maternal behavior related to the pups at parturition. From the nine experimental groups studied, only pre- and perinatal TD dams exhibited spontaneous abortion (33.36 and 41.66%, respectively) followed by pups-killing responses where, respectively, 4 dams/7 (57.14%) and 5 dams/7 (71.43%) showed disruption of maternal behavior and appearance of cannibalism towards pups which all were killed within 48 hours after parturition. Spontaneous abortion and pup-killing responses were not observed in the dams of any other experimental group, suggesting that perinatal disturbances of hormonal factors underlay these maternal disorders. Previous studies reported that thiamine deficiency-induced degeneration of dopamine neurons may be related to mouse-killing aggression in rats. The present study suggests that perinatal thiamine deficiency-induced alteration of dopaminergic neurons in maternal brain could be a trigger factor of pup-killing responses. Central dopamine and oxytocin have been strongly associated with both the onset and maintenance of maternal behavior and the regulation of maternal aggressiveness as well. Our studies suggest that estrogen control oxytocin levels in brain structures of pregnancy-terminated rats via dopamine transmission. Thiamine

  13. Early retinal blood vessel growth in normal and growth restricted rat pups raised in oxygen and room air.

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    Dhaliwal, C A; Wade, J; Gillespie, T; Aspinall, P; McIntosh, N; Fleck, B W

    2011-11-01

    Premature infants are born with incompletely vascularised retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of prenatal and postnatal body growth is important in the pathogenesis of ROP. The aim of this study was to develop a physiology-based rat model in order to study the effect of growth restriction and oxygen on early retinal vascular development. Rat mothers were fed either a normal (18% casein) or low (9% casein) protein diet (to cause pup growth restriction) from the last week of gestation. After birth, mother and pups were placed in either room air or a specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen profile. The oxygen profile was based on that from a premature infant who developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained using biotinylated lectin. Images were captured by confocal microscopy. The avascular areas of the retinas were measured and compared. Growth restricted rat pups had significantly larger retinal avascular areas than 'normally grown' rat pups (Mann-Whitney U test, pair (Mann-Whitney U test, p=0.001). The authors have developed a novel model for ROP that involves inducing both intrauterine and postnatal growth restriction and also exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can be used to study the effects of growth, nutrition and oxygen on early retinal vascular development.

  14. Nicotine exposure affects mother's and pup's nutritional, biochemical, and hormonal profiles during lactation in rats.

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    Oliveira, E; Pinheiro, C R; Santos-Silva, A P; Trevenzoli, I H; Abreu-Villaça, Y; Nogueira Neto, J F; Reis, A M; Passos, M C F; Moura, E G; Lisboa, P C

    2010-05-01

    We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats divided into two groups: NIC - continuous s.c. infusions of nicotine (6 mg/kg per day) for 14 days and C - saline. Dams and pups were killed at 15 and 21 days of lactation. Body weight and food intake were evaluated. Milk, blood, visceral fat, carcass, and adrenal gland were collected. All the significant data were Pmilk production, hyperprolactinemia, and higher serum high-density lipoprotein cholesterol (HDL-C). Milk from NIC dams had higher lactose concentration and energy content. After nicotine withdrawal (21 days), dams showed lower food intake and hyperleptinemia. The 15-day-old NIC pups presented higher total body fat, higher HDL-C, serum leptin, serum corticosterone, and adrenal catecholamine content, but lower tyrosine hydroxylase protein levels. The 21-day-old NIC pups had higher body protein content and serum globulin. Thus, maternal nicotine exposure during lactation results in important changes in nutritional, biochemical, and hormonal parameters in dams and offspring. The pattern of these effects is clearly distinct when comparing the nicotine-exposed group to the withdrawal group, which could be important for the programming effects observed previously.

  15. Novel husbandry techniques support survival of naked mole rat (Heterocephalus glaber) pups.

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    Ke, Zhonghe; Vaidya, Amita; Ascher, Jill; Seluanov, Andrei; Gorbunova, Vera

    2014-01-01

    The naked mole rat (NMR) is a small eusocial rodent. Because of its remarkable longevity (maximal lifespan, 32 y) and resistance to cancer, the NMR has emerged as a valuable model for aging and cancer research. However, breeding NMR can be difficult. Here, we report the successful introduction and acceptance of pups into a foreign colony with existing pups of different ages. Among the 7 NMR colonies in our satellite facility, one had a consistently poor record of pup viability, with nearly 100% preweaning mortality in multiple litters born over the course of 2 y. The queen of this colony gave birth to 18 pups in January 2013; by 2 d after parturition, it was evident that the pups were not receiving sufficient nourishment. To salvage the litter, the most vigorous pups were cross-fostered to another queen that had recently given birth. On postparturition day 1 (PD1), two pups from the poorly nourished donor litter were bathed with warm water, rolled in recipient colony bedding, and transferred to the recipient colony, which included 8 PD14 pups. The new pups were accepted by the recipient queen, who continued to produce milk in response to suckling by the donor pups well past the weaning of her own litter. This case report provides evidence of successful cross-fostering of NMR pups despite age differences between donor pups and those in the recipient litter; this technique may prove beneficial to researchers struggling with NMR breeding issues.

  16. Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups.

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    Mochizuki, Masahiro; Shimizu, Satomi; Kidokoro, Yuri; Kamata, Takashi; Kitazawa, Takahiro; Kishi, Daisuke; Okazaki, Emi; Nishihata, Yoshito; Ohishi, Takumi

    2009-12-01

    Effects of repeated administration of phenobarbital (PB) on blood coagulation-related parameters were examined in non-pregnant, pregnant and lactating rats, and also in pups born to PB-treated lactating dams. PB was orally administered at a dose level of 80 mg/kg/day to pregnant (from gestation day (GD) 13), postpartum (from postpartum day (PPD) 7) and non-pregnant rats (from 13 weeks of age) for 7 days. Blood was collected on GD20 or PPD14 to perform blood coagulation examination. Concurrently, the blood coagulation parameters were examined in the pups. Increases in liver weight and/or hepatic cytochrome P450 content were observed in the PB-treated non-pregnant, pregnant and lactating rats. Activated partial thromboplastin time (APTT) was prolonged and anti-thrombin III (ATIII) concentration was increased in the lactating rats, while there were no changes in prothrombin time (PT) or APTT in the non-pregnant and pregnant rats. Moreover, prolongation of PT and APTT and decreases in factors VII and IX activities were observed in their pups. Thus, prolongation of blood coagulation time was confirmed in both dams and their pups following PB-administration to lactating dams. Effects of vitamin K(2) (VK(2)) on PB-induced changes in blood coagulation-related parameters of both dams and their pups were examined by co-administration with PB and VK(2) to lactating dams. PT and APTT were comparable to the control and PB-induced prolongation of blood coagulation time was improved in the pups while APTT was prolonged in dams, suggesting that VK(2) was beneficial to pups but not to dams.

  17. [Pup-Associated Conditioned Place Preference and Maternal Behavior in Depressive WAG/Rij Rats].

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    Sarkisova, K Yu; Tanaeva, K K; Dobryakova, Yu V

    2016-01-01

    Elaboration of conditioned place preference (CPP) associated with own and foster pups, and maternal behavior were compared in females of WAG/Rij and Wistar rats. In addition, behavior of females in the open field, elevated plus-maze and forced swimming tests were investigated before pregnancy and after pup delivery. In has been found that females of WAG/Rij rats elaborate worse CPP task associated with both their own (WAG/Rij) and foster (Wistar) pups. Thus, the number of females that increase time spent in initially non-preferred compartment after its association with pups and the number of females that reach criterion of CPP elaboration in WAG/Rij rats were less than in Wistar controls. WAG/Rij females exhibited less maternal care in the place preference test both to their own and foster pups: less number of approaches to pups, pups carrying and the time spent in contact with pups non-associated with feeding. In WAG/Rij females compared with Wistar controls immobility time in the forced swimming test was higher both before pregnancy and after pup delivery indicating a stable depression-like state. Before pregnancy, statistically significant inter-strain differences in the anxiety level have not been revealed. After pup delivery, in WAG/Rij females anxiety level decreased but in Wistar females didn't substantially change. Results suggest that worse elaboration of CPP task and reduced maternal care in depressive WAG/Rij females are not associated with specific features of their own pups but are due to their depression-like state. Put into other words, pups for depressive mothers are less potent reinforcer than for "normal" (non-depressive) mothers.

  18. Oral administration of deuterium-labelled polyamines to sucking rat pups : luminal uptake, metabolic fate and effects on gastrointestinal maturation

    NARCIS (Netherlands)

    Dorhout, B; van Faassen, A; van Beusekom, C M; Kingma, A W; de Hoog, E; Nagel, G T; Karrenbeld, A; Boersma, E R; Muskiet, F A

    1997-01-01

    Non-physiological amounts of oral polyamines have been reported to induce precocious gut maturation in rat pups. The aim of the present study was to investigate organ distribution and metabolic fate of orally administered stable-isotopically labelled polyamines in rat pups. Pups received tetradeuter

  19. Ethological analysis of mother-pup interactions and other behavioral reactions in rats: effects of malnutrition and tactile stimulation of the pups

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    Riul T.R.

    1999-01-01

    Full Text Available Mother-pup interaction, as well as other behavioral reactions were studied during the lactation period in 24 litters of Wistar rats and their dams fed either a 16% (control - C; 12 litters or a 6% (malnourished - M; 12 litters protein diet. The diets were isocaloric. Throughout lactation there was a 36.4% weight loss of M dams and a 63% body weight deficit in the M pups when compared to control pups. During this period, half of the litters were exposed daily to additional tactile stimulation (CS or MS, while the other half were submitted to normal rearing conditions (CN or MN. The tactile stimulation of pups (handling consisted of holding the animal in one hand and gently touching the dorsal part of the animal's body with the fingers for 3 min. A special camera and a time-lapse video were used to record litter behavior in their home cages. Starting at 6 p.m. and ending at 6 a.m., on days 3, 6, 12, 15, 18 and 21 of lactation, photos were taken at 4-s intervals. An increase in the frequency (154.88 ± 16.19 and duration (455.86 ± 18.05 min of suckling was observed throughout the lactation period in all groups compared to birth day (frequency 24.88 ± 2.37 and duration 376.76 ± 21.01 min, but the frequency was higher in the C (84.96 ± 8.52 than in the M group (43.13 ± 4.37; however, the M group (470.2 ± 11.87 min spent more time suckling as compared with the C group (393.67 ± 13.09 min. The M dams showed a decreased frequency of resting position throughout the lactation period (6.5 ± 2.48 compared to birth day (25.42 ± 7.74. Pups from the C group were more frequently observed separated (73.02 ± 4.38 and interacting (258.99 ± 20.61 more with their mothers than the M pups (separated 66.94 ± 5.5 and interacting 165.72 ± 12.05. Tactile stimulation did not interact with diet condition, showing that the kind of stimulation used in the present study did not lead to recovery from the changes induced by protein malnutrition. The changes in

  20. Labor Contractions Enhance Oxygenation and Behavioral Activity of Newborn Rat Pups

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    Mills, N. A.; Baer, L. A.; Ronca, A. E.; Balton, Bonnie (Technical Monitor)

    2002-01-01

    Labor contractions help instigate behavioral responses at birth (viz., breathing and suckling) that are vital for the newborn's adaptation to the extrauterine world (Ronca et al., 1996). In the present study, we analyzed the role of labor contractions in postpartum oxygenation and behavioral activity of newborn rat pups. Newborns were observed following either vaginal (V) or cesarean delivery. For cesarean delivery, day 21 pregnant dams' were administered a spinal transaction to eliminate lower body sensation, a laparotomy was performed and the uterus was maintained in a heated (37.5 C) bath. Four rat fetuses in one of the dams' paired uterine horn were compressed (C) to Simulate labor contractions (20 sec/min for 10 min) while four fetuses in the opposite horn were not compressed (NC). Fetuses were surgically removed from the uterus, stroked with a soft brush to mimic postnatal licking by the dam, the umbilical cord occluded. Pups were exposed to room temperature (22 C) for one hr, then nest temperature (33 C) for one hr. PO2, CO2, and O2, saturation were determined at 0, 30, 60, or 120 min post delivery using a blood gas analyzer. V and C delivered neonates showed comparable rates of PO2, CO2 and O2 saturation whereas NC neonates showed depressed levels at all time points (pcontractions in early postpartum adaptation.

  1. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

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    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

  2. Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ERα, ERβ), oxytocin and serotonin (5-HT1A) in their brain.

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    Stamatakis, Antonios; Kalpachidou, Theodora; Raftogianni, Androniki; Zografou, Efstratia; Tzanou, Athanasia; Pondiki, Stavroula; Stylianopoulou, Fotini

    2015-02-01

    In the present study we investigated the neurobiological mechanisms underlying expression of maternal behavior. Increased maternal behavior was experimentally induced by a brief 15-min separation between the mother and the pups during postnatal days 1 to 22. On postnatal days (PND) 12 and 22, we determined in experimental and control dams levels of anxiety in the elevated plus maze (EPM) as well as the levels of receptors for estrogens (ERα, ERβ), oxytocin (OTR) and serotonin (5-HT1AR) in areas of the limbic system (prefrontal cortex-PFC, hippocampus, lateral septum-SL, medial preoptic area-MPOA, shell of nucleus accumbens-nAc-Sh, central-CeA and basolateral-BLA amygdala), involved in the regulation of maternal behavior. Experimental dams, which showed increased maternal behavior towards their offspring, displayed reduced anxiety in the EPM on both PND12 and PND22. These behavioral differences could be attributed to neurochemical alterations in their brain: On both PND12 and PND22, experimental mothers had higher levels of ERα and OTRs in the PFC, hippocampus, CeA, SL, MPOA and nAc-Sh. The experimental manipulation-induced increase in ERβ levels was less widespread, being localized in PFC, the hippocampal CA2 area, MPOA and nAc-Sh. In addition, 5-HT1ARs were reduced in the PFC, hippocampus, CeA, MPOA and nAc-Sh of the experimental mothers. Our results show that the experience of the daily repeated brief separation from the pups results in increased brain ERs and OTRs, as well as decreased 5-HT1ARs in the dam's brain; these neurochemical changes could underlie the observed increase in maternal behavior and the reduction of anxiety.

  3. Differential responses in the lungs of newborn mouse pups exposed to 85% or >95% oxygen.

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    Rogers, Lynette K; Tipple, Trent E; Nelin, Leif D; Welty, Stephen E

    2009-01-01

    Premature infants often develop serious clinical complications associated with respiratory failure and hyperoxic lung injury that includes lung inflammation and alterations in lung development. The goal of these studies is to test the hypothesis that there are differences in the course of lung injury in newborn mice exposed to 85% or >95% oxygen that provide models to address the differential effects of oxidation and inflammation. Our results indicate differences between the 85% and >95% O2 exposure groups by day 14 in weight gain and lung alveolarization. Inflammation, assessed by neutrophil counts, was observed in both hyperoxia groups by day 3 but was dramatically greater in the >95% O2-exposed groups by day 14 and associated with greater developmental deficits. Cytoplasmic phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase levels were elevated but no patterns of differences were observed between exposure groups. Prostaglandins D2, E2, and F2alpha were increased in the tissues from mouse pups exposed to >95% O2 at 7 d indicating a differential expression of cyclooxygenase-2 products. Our data indicate that there are differences in the models of 85% or >95% O2 exposure and these differences may provide mechanistic insights into hyperoxic lung injury in an immature system.

  4. Differential Responses in the Lungs of Newborn Mouse Pups Exposed to 85% or >95% Oxygen

    Science.gov (United States)

    Rogers, Lynette K.; Tipple, Trent E.; Nelin, Leif D.; Welty, Stephen E.

    2008-01-01

    Premature infants often develop serious clinical complications associated with respiratory failure and hyperoxic lung injury that include lung inflammation, and alterations in lung development. The goal of these studies is to test the hypothesis that there are differences in the course of lung injury in newborn mice exposed to 85% or >95% oxygen that provide models to address the differential effects of oxidation and inflammation. Our results indicate differences between the 85% and >95% O2 exposure groups by day 14 in weight gain and lung alveolarization. Inflammation, assessed by neutrophil counts, was observed in both hyperoxia groups by day 3 but was dramatically greater in the >95% O2 exposed groups by day 14 and associated with greater developmental deficits. Cytoplasmic phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase levels were elevated but no patterns of differences were observed between exposure groups. Prostaglandins (PG) D2, E2, and F2α were increased in the tissues from mouse pups exposed to >95% O2 at 7 days indicating a differential expression of COX-2 products. Our data indicate that there are differences in the models of 85% or >95% O2 exposure and these differences may provide mechanistic insights into hyperoxic lung injury in an immature system. PMID:18703992

  5. Increased ultrasonic vocalizations and risk-taking in rat pups of sleep-deprived dams.

    Science.gov (United States)

    Gulia, Kamalesh K; Patel, Niraj; Kumar, Velayudhan Mohan

    2015-02-01

    Ultrasonic vocalizations (USVs) in rodent pups are analogous to cries in human babies. There is reduction in USVs in pups after experimental deprivation of rapid eye movement sleep of dams during pregnancy. However, the effects of total sleep deprivation on the USVs of newborns and their emotional development are not documented. Male pups born to the rats that underwent total sleep deprivation for 5h during the third trimester made higher vocalizations, when tested on early postnatal days (pnds) in an isolation-paradigm. Their anxiety-related behaviors during pnds 25-28, were tested using elevated plus maze (EPM). In comparison to the control pups, weanlings of sleep-deprived dams made increased entries into the open arms and higher mobility in the EPM. Enhanced distress calls during early pnds and reduction in risk assessment in weanlings indicate a link between the two behaviors. The USVs during ontogeny may provide early signals about altered emotional development.

  6. Amniotic fluid-borne hepatocyte growth factor protects rat pups against experimental necrotizing enterocolitis.

    Science.gov (United States)

    Jain, Sunil K; Baggerman, Eric W; Mohankumar, Krishnan; Namachivayam, Kopperuncholan; Jagadeeswaran, Ramasamy; Reyes, Victor E; Maheshwari, Akhil

    2014-03-01

    Fetal swallowing of amniotic fluid, which contains numerous cytokines and growth factors, plays a key role in gut mucosal development. Preterm birth interrupts this exposure to amniotic fluid-borne growth factors, possibly contributing to the increased risk of necrotizing enterocolitis (NEC) in premature infants. We hypothesized that supplementation of formula feeds with amniotic fluid can provide amniotic fluid-borne growth factors and prevent experimental NEC in rat pups. We compared NEC-like injury in rat pups fed with infant formula vs. formula supplemented either with 30% amniotic fluid or recombinant hepatocyte growth factor (HGF). Cytokines/growth factors in amniotic fluid were measured by immunoassays. Amniotic fluid and HGF effects on enterocyte migration, proliferation, and survival were measured in cultured IEC6 intestinal epithelial cells. Finally, we used an antibody array to investigate receptor tyrosine kinase (RTK) activation and immunoblots to measure phosphoinositide 3-kinase (PI3K) signaling. Amniotic fluid supplementation in oral feeds protected rat pups against NEC-like injury. HGF was the most abundant growth factor in rat amniotic fluid in our panel of analytes. Amniotic fluid increased cell migration, proliferation, and cell survival in vitro. These effects were reproduced by HGF and blocked by anti-HGF antibody or a PI3K inhibitor. HGF transactivated several RTKs in IEC6 cells, indicating that its effects extended to multiple signaling pathways. Finally, similar to amniotic fluid, recombinant HGF also reduced the frequency and severity of NEC-like injury in rat pups. Amniotic fluid supplementation protects rat pups against experimental NEC, which is mediated, at least in part, by HGF.

  7. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

    Science.gov (United States)

    Kim, P A; Voskresenskaya, O G; Kamensky, A A

    2009-06-01

    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  8. Diphenyl ditelluride induces neurotoxicity and impairment of developmental behavioral in rat pups

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    Pinton, Simone; Luchese, Cristiane; Stangherlin, Eluza C.; Roman, Silvane S.; Nogueira, Cristina W., E-mail: criswn@quimica.ufsm.b [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Centro de Tecnologia. Dept. de Quimica

    2010-07-01

    The purpose of the present study was to investigate if acute exposure to diphenyl ditelluride (PhTe){sub 2} causes impairment of developmental behavioral performance in rat pups. Rat pups received a single subcutaneous injection of (PhTe){sub 2} (0.1 mg kg{sup -1}, 3 mL kg{sup -1}) or vehicle (3 mL kg{sup -1}) at 14th postnatal day. After exposure to (PhTe){sub 2}, the general parameters of neurotoxicity, behavioral tasks, cerebral myelin content, histological analysis and acetylcholinesterase (AChE) activity were performed during seven days. The appearance of classic signs of toxicity, behavioral alterations and the reduction in myelin content were dependent on the time after (PhTe){sub 2} exposure to pups. Neuronal damage, reduction of myelin content, and the increase in AChE activity occurred mainly at 4th and 5th day after (PhTe){sub 2} exposure, indicating that the critical period of neurotoxicity is coincident with the major behavioral alterations. In conclusion, exposure to (PhTe){sub 2} induced neurotoxicity and impairment of developmental behavioral in rat pups. (author)

  9. Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning

    Directory of Open Access Journals (Sweden)

    Vilà Ruth

    2008-06-01

    Full Text Available Abstract Background In rats, oral oleoyl-estrone (OE decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. Methods Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day. Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. Results Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. Conclusion The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood.

  10. Treadmill exercise ameliorates motor disturbance through inhibition of apoptosis in the cerebellum of valproic acid-induced autistic rat pups.

    Science.gov (United States)

    Kim, Ji-Eun; Shin, Mal-Soon; Seo, Tae-Beom; Ji, Eun-Sang; Baek, Seong-Soo; Lee, Sam-Jun; Park, Joon-Ki; Kim, Chang-Ju

    2013-08-01

    Autism is a neurological disorder that occurs during childhood and is characterized by impairments in social interaction and communication, as well as restricted and repetitive behaviors. Abnormalities of the cerebellum in autism include Purkinje cell loss and motor disturbance. In the present study, we evaluated the effect of treadmill exercise on motor coordination and balance in correlation with reelin expression and the rate of apoptosis in the cerebellum of autistic rat pups. For the induction of the autism-like animal models, 400 mg/kg valproic acid was subcutaneously injected into rat pups on postnatal day 14. Rat pups in the exercise groups were forced to run on a treadmill for 30 min, once a day, five times a week for 4 weeks, starting on postnatal day 28. Motor coordination and balance, as measured using the rotarod test and vertical pole test, were affected by the induction of autism. By contrast, treadmill exercise ameliorated motor dysfunction in the autistic rat pups. The expression levels of reelin, GAD67 and cyclin D1 in the cerebellum of the autistic rat pups were decreased, while the expression levels of these molecules were increased in autistic rat pups who engaged in treadmill exercise. In the cerebellum of the autistic rat pups, Bcl-2 expression was decreased and Bax expression was increased. By contrast, treadmill exercise enhanced Bcl-2 expression and suppressed Bax expression. The therapeutic effect of treadmill exercise on motor deficits may be due to the reelin-mediated anti-apoptotic effect on cerebellar Purkinje neurons.

  11. Lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) causes hyperactivity in male rat pups by aberrant increase in dopamine and its receptor.

    Science.gov (United States)

    Lesmana, Ronny; Shimokawa, Noriaki; Takatsuru, Yusuke; Iwasaki, Toshiharu; Koibuchi, Noriyuki

    2014-08-01

    Polychlorinated biphenyls (PCBs) are recognized as persistent environmental pollutants that may cause adverse health problems. Despite extensive investigations of PCB in neural function, little is known about behavioral traits by PCB exposure and its neurochemical mechanism. Here, we report the behavioral study of a rat pup that was exposed to hydroxylated-PCB 106 (OH-PCB 106; 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl) through maternal milk. The different groups of mothers received via gavage corn oil vehicle, 0.5, 5, or 50 mg/kg body weight of OH-PCB 106 every second day from day 3 to 13 after delivery. The exposure did not affect the body weight of the dams or the physical development of the newborn pups in both sexes. Male rats exposed to OH-PCB 106 showed hyperactivity that was characterized by increased locomotor activity in novel environment and circadian period. Interestingly, OH-PCB 106-exposed rat pups displayed abnormally high levels of dopamine and D2 dopamine receptor (D2DR), but not D1DR and D5DR, in the striatum, an important center for the coordination of behavior. These findings indicate that OH-PCB 106 has a significant neurotoxic effect on rat behavior, which may be associated with increased D2DR mediated signals.

  12. Serotonergic and noradrenergic lesions suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups.

    Science.gov (United States)

    Akhavan, M M; Emami-Abarghoie, M; Safari, M; Sadighi-Moghaddam, B; Vafaei, A A; Bandegi, A R; Rashidy-Pour, A

    2008-02-19

    The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase of the pups' learning. Maternal forced swimming by pregnant rats increased both acquisition and retention phases of the pups' learning. Also we found that the rat pups whose mother was submitted to forced-swimming during pregnancy had significantly higher brain, liver, heart and kidney weights compared with their sedentary counterparts. On the other hand we estimated the cell number of different regions of the hippocampus in the rat pups. We found that both exercise models during pregnancy increased the cell number in cornus ammonis subregion 1 (CA1) and dentate gyrus of the hippocampus in rat pups. To determine the role that noradrenergic and serotonergic neurotransmission and N-methyl-D-aspartate (NMDA) receptors hold in mediation of the maternal exercise in offspring, we used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), p-chloroamphetamine (PCA) and MK-801 to eliminate or block the above systems, respectively. Blocking the NMDA receptors, significantly abolished learning and memory in rat pups from all three experimental groups. Elimination of noradrenergic or serotonergic input did not significantly attenuate the learning and memory in rat pups whose mothers were sedentary, while it significantly reversed the positive effects of maternal exercise during pregnancy on rat pups' learning and memory. The presented results suggest that noradrenergic and serotonergic systems in offspring brain seem to have a crucial specific role in mediating the effects of maternal physical activity during pregnancy on rat pups' cognitive function in both models of voluntary and forced exercise.

  13. Repeated Long Separations from Pups Produces Depression-like Behavior in Rat Mothers

    Science.gov (United States)

    Boccia, Maria L.; Razzoli, Maria; Vadlamudi, Sivaram Prasad; Trumbull, Whit; Caleffie, Christopher; Pedersen, Cort A.

    2007-01-01

    Summary Long (LMS) versus brief (BMS) daily separations of rat pups from their mothers have contrasting effects on their adult stress responses and maternal behavior by respectively decreasing and increasing licking received from their mothers. We hypothesized that LMS decreases pup licking in mothers by inducing learned helplessness, creating a depression-like state. We subjected postpartum rats to LMS (3 h), BMS (15 min) or no separation (NMS) on postpartum days 2–14. After weaning, mothers were given a forced swim test (FST). LMS mothers exhibited more immobility and fewer escape attempts than BMS or NMS mothers. These results suggest that LMS induces a depression-like state, which may account for the reductions in maternal behavior seen in LMS mothers. Immobility in the FST is recognized as an animal model of depression. Therefore, LMS may be a model of maternal depression. PMID:17118566

  14. Epac Activation Initiates Associative Odor Preference Memories in the Rat Pup

    Science.gov (United States)

    Grimes, Matthew T.; Powell, Maria; Gutierrez, Sandra Mohammed; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

    2015-01-01

    Here we examine the role of the exchange protein directly activated by cAMP (Epac) in ß-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac…

  15. Nootropic and antiamnestic effects of tenoten (pediatric formulation) in immature rat pups.

    Science.gov (United States)

    Voronina, T A; Molodavkin, G M; Borodavkina, M V; Kheyfets, I A; Dugina, Yu L; Sergeeva, S A

    2009-09-01

    The antiamnestic effects of tenoten (pediatric formulation) was demonstrated on the model of scopolamine-induced amnesia of passive avoidance reflex and the nootropic effect of this preparation was demonstrated on the model of incomplete conditioning and in rat pups with experimental attention deficit syndrome. The efficiency of the preparation was comparable to that of piracetam and phenibut and even surpassed it by some parameters.

  16. Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

    Science.gov (United States)

    Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-08-01

    Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.

  17. Oxidative stress and alteration of biochemical markers in liver and kidney by malathion in rat pups.

    Science.gov (United States)

    Selmi, Slimen; El-Fazaa, Saloua; Gharbi, Najoua

    2015-09-01

    The present study was undertaken to determine the effects of malathion exposure through maternal milk on oxidative stress, functional an metabolic parameters in kidney and liver of rat pups. We found that lactational exposure to malation (200 mg/kg, body weight (bw)) induced an oxidative stress status assessed by an increase in malondialdhyde (MDA) content, reflecting lipoperoxidation, a decrease in thiol groups' content as well as depletion of enzyme activities as a superoxide dismutase (SOD) and catalase (CAT) on postnatal days (Pnds) 21 and 51. Moreover, the current study showed that malathion induced liver and kidney dysfunctions demonstrated by considerable increase in phosphatase alkaline (PAL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as total and direct bilirubin, creatinine urea and acid uric contents. We also observed an increase in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in the plasma of treated rat pups. These findings evidenced that malathion exposure during lactation through maternal milk of rats pups induced kidney and liver oxidative stress as well as functional and metabolic disorders that play a role in the development of others pathologies as cardiovascular diseases and cancers.

  18. Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups

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    Adaweyah El-Merhibi

    2012-01-01

    Full Text Available There are conflicting data to support the practice of delaying the introduction of allergenic foods into the infant diet to prevent allergy development. This study investigated immune response development after early oral egg antigen (Ovalbumin; OVA exposure in a rat pup model. Brown Norway (BN rat pups were randomly allocated into groups: dam reared (DR, DR pups challenged daily (days 4–13 with oral OVA (DR + OVAc, DR pups challenged intermittently (on day 4, 10, 12, and 13 with oral OVA (DR + OVAi, formula-fed pups (FF, and FF pups challenged daily with oral OVA (FF + OVA. Immune parameters assessed included OVA-specific serum IgE, IgG1, and IgA. Ileal and splenic messenger ribonucleic acid (mRNA expression of transforming growth factor-beta (TGF-β1, mothers against decapentaplegic (Smad 2/4/7, and forkhead box P3 (Foxp3 were determined. Ileum was stained for TGF-β1 and Smad4. Results. Feeding OVA daily to DR pups maintained systemic and local gut antibody and immunoregulatory marker mRNA responses. Systemic TGF-β1 was lower in DR + OVAi pups compared to DR and DR + OVAc pups. Feeding OVA to FF pups resulted in significantly greater OVA-specific IgE and IgG1, and lower IgA and TGF-β1 and Smad expression compared to DR pups. Conclusions. Early daily OVA exposure in the presence of maternal milk maintains immune markers associated with a regulated immune response, preventing early allergic sensitization.

  19. Prenatal cocaine exposure induces deficits in Pavlovian conditioning and sensory preconditioning among infant rat pups.

    Science.gov (United States)

    Heyser, C J; Chen, W J; Miller, J; Spear, N E; Spear, L P

    1990-12-01

    Offspring derived from Sprague-Dawley dams that received daily subcutaneous injection of 40 mg/kg.3 cc-1 cocaine hydrochloride (C40) or saline (LC) from Gestational Days 8-20 were tested for first-order Pavlovian conditioning and sensory preconditioning at Postnatal Days 8 (P8), P12, and P21. Although C40 dams gained significantly less weight than LC dams, pup body weights did not differ between the two groups. Significant sensory preconditioning was obtained at P8 and P12 (but not at P21) in LC offspring, confirming previous reports of decline in performance in this task during ontogeny. In contrast, C40 offspring failed to exhibit sensory preconditioning at any test age. In addition, C40 pups tested at P8 did not display significant first-order conditioning. Taken together these results suggest a more general deficit in cognitive functioning rather than a delay in cognitive development in prenatally cocaine-exposed offspring.

  20. Behavioral and pharmacological investigation of anxiety and maternal responsiveness of postpartum female rats in a pup elevated plus maze.

    Science.gov (United States)

    Yang, Yu; Qin, Jingxue; Chen, Weihai; Sui, Nan; Chen, Hong; Li, Ming

    2015-10-01

    The present study investigated the validity of a novel pup-based repeated elevated plus maze task to detect reduced anxiety and increased maternal responsiveness in postpartum female rats and explored the roles of dopamine D2, serotonin transporter and GABA/benzodiazepine receptors in the mediation of these processes. Sprague-Dawley postpartum or nulliparous female rats were tested 4 times every other day on postpartum days 4, 6 and 8 in an elevated plus maze with 4 pups or 4 pup-size erasers placed on each end of the two open arms. When tested with erasers, untreated postpartum mother rats entered the open arms proportionally more than nulliparous rats. They also tended to spend more time in the open arms, indicating reduced anxiety. When tested with pups, postpartum rats retrieved pups into the closed arms, entered the open arms and closed arms more and had a higher moving speed than nulliparous rats, indicating increased maternal responsiveness. Both haloperidol (0.1 or 0.2 mg/kg, sc) and fluoxetine (5 or 10 mg/kg, ip) dose- and time-dependently decreased the percentage of time spent in the open arms and speed, but did not affect the percentage of open arm entries. Diazepam (1.0 or 2.0 mg/kg, ip) did not affect pup retrieval, open arm time/entry in lactating rats. Thus, the percentage of open arm entries appears to be the most sensitive measure of anxiety in postpartum female rats, while speed could be used to index maternal responsiveness to pups, which are likely mediated by the dopamine D2 and serotonin transporter systems.

  1. Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Boberg, Julie

    2010-01-01

    Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development......, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Consequently, we have initiated a large project where the purpose is to study mixture effects of endocrine disrupting pesticides at low doses. In the initial range-finding mixture studies, rats...... were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup...

  2. The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups

    Directory of Open Access Journals (Sweden)

    Menshanov Petr N.

    2015-09-01

    Full Text Available In vivo study of cerebral metabolism in neonatal animals by high-resolution magnetic resonance spectroscopy (MRS is an important tool for deciphering the developmental origins of adult diseases. Up to date, all in vivo spectrum acquisition procedures have been performed in neonatal rodents under anesthesia. However, it is still unknown if the inhaled anesthetic isoflurane, which is commonly used in magnetic resonance imaging studies, could affect metabolite levels in the brain of neonatal rats. Moreover, the unanesthetized MRS preparation that uses neonatal rodent pups is still lacking.

  3. A rat pup model of cerebral palsy induced by prenatal inflammation and hypoxia

    Institute of Scientific and Technical Information of China (English)

    Yanrong Hu; Feng Gao; Jianxin Li; Lihui Zhao; Gang Chen; Hong Wan; Zhiyou Zhang; Hong Zhi; Wei Liu; Xinwei Qian; Mingzhao Chen; Linbao Wen

    2013-01-01

    Animal models of cerebral palsy established by simple infection or the hypoxia/ischemia method cannot effectively simulate the brain injury of a premature infant. Healthy 17-day-pregnant Wistar rats were intraperitoneally injected with lipopolysaccharide then subjected to hypoxia. The pups were used for this study at 4 weeks of age. Simultaneously, a hypoxia/ischemia group and a control group were used for comparison. The results of the footprint test, the balance beam test, the water maze test, neuroelectrophysiological examination and neuropathological examination demonstrated that, at 4 weeks after birth, footprint repeat space became larger between the forelimbs and hindlimbs of the rats, the latency period on the balance beam and in the Morris water maze was longer, place navigation and ability were poorer, and the stimulus intensity that induced the maximal wave amplitude of the compound muscle action potential was greater in the lipopolysaccharide/hypoxia and hypoxia/ischemia groups than in the control group. We observed irregular cells around the periventricular area, periventricular leukomalacia and breakage of the nuclear membrane in the lipopolysaccharide/hypoxia and hypoxia/ischemia groups. These results indicate that we successfully established a Wistar rat pup model of cerebral palsy by intraperitoneal injection of lipopolysaccharide and hypoxia.

  4. Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups.

    Science.gov (United States)

    Yazdani, Armin; Khoja, Zehra; Johnstone, Aaron; Dale, Laura; Rampakakis, Emmanouil; Wintermark, Pia

    2016-01-01

    Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

  5. Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats.

    Science.gov (United States)

    Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

    2014-08-01

    During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.

  6. Short-term effects of a perinatal exposure to the HBCDD α-isomer in rats: Assessment of early motor and sensory development, spontaneous locomotor activity and anxiety in pups.

    Science.gov (United States)

    Maurice, Nicolas; Olry, Jean-Charles; Cariou, Ronan; Dervilly-Pinel, Gaud; Le Bizec, Bruno; Travel, Angélique; Jondreville, Catherine; Schroeder, Henri

    2015-01-01

    The present study investigated the developmental neurotoxicity of an early exposure to α-HBCDD through the ingestion of contaminated hen's egg in pregnant and lactating Wistar female rats. Hens were given α-HBCDD-contaminated feed (40 ng/g fresh matter) for 5 and 10 days, which produced eggs with HBCDD content of 33 and 102 ng/glipid weight, respectively. Female rats were administered daily p.o. with an appropriate volume of the whole egg from the day of fertilization (GD0) to the weaning day for pups (PND21). Fetuses and pups were thus exposed continuously to α-HBCDD via the dam over a whole 42-day period that included both gestation and lactation. The administered egg volume was calculated on the basis of daily egg consumption in humans (0.7 egg/person/day) and duration of gestation and lactation in both species, which led animals to be exposed to α-HBCDD at levels of 22 and 66 ng/kg/day, respectively. Neurobehavioral development of pups was investigated from PND3 to PND25 using various tasks including the righting reflex (PND4), the grasping reflex (PND5), the negative geotaxis (PND9), the forelimb grip strength test (PND10) and the locomotor coordination test (PND20). Pup ultrasonic vocalizations were also recorded daily from PND4 to PND14. After weaning, behaviors related to spontaneous locomotor activity and anxiety were examined in the open-field (PND25) and in an elevated-plus maze (PND26), respectively. The results showed a significant decrease in body weight of pups exposed to the lower HBCDD level from PND3 to PND28, whereas the weight of rat pups given 66 ng/kg/day of HBCDD was not different from controls. During the first 3 weeks of life, impairments in motor maturation of pups were observed in a dose-dependent manner depending on the test, whereas no significant differences were reported between male and female pups. At PND26, the anxiety level of female rats exposed to the lowest dose of HBCDD (22 ng/kg/day) was significantly reduced whereas it

  7. Adverse effects of melatonin on rat pups of Wistar-Kyoto dams receiving melatonin supplementation during pregnancy.

    Science.gov (United States)

    Singh, Harbindar Jeet; Keah, Lee Siew; Kumar, Arun; Sirajudeen, K N S

    2012-11-01

    This report documents an incidental finding during a study investigating the effects of melatonin supplementation on the development of blood pressure in SHR. Administration of 10 mg/kg/day of melatonin in drinking water during pregnancy to Wistar-Kyoto (WKY) dams caused a loss of more than 50% of the pups by the age of three weeks and 95% by the age of 6 weeks. There was no maternal morbidity or mortality in the two strains or death of any of the SHR pups. No obvious physical defects were present but mean body weight was lower in the surviving WKY rats when compared to that of melatonin supplemented SHR or non-supplemented WKY pups. The reason for the high mortality in WKY pups is uncertain and appears to be strain if not batch specific. There is a need for caution in its use, particularly during pregnancy, and clearly necessitates more detailed studies.

  8. Maternal swimming during pregnancy enhances short-term memory and neurogenesis in the hippocampus of rat pups.

    Science.gov (United States)

    Lee, Hee-Hyuk; Kim, Hong; Lee, Jin-Woo; Kim, Young-Sick; Yang, Hye-Young; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Shin, Min-Chul; Lee, Myoung-Hwa; Shin, Mal-Soon; Park, Sooyeon; Baek, Seungsoo; Kim, Chang-Ju

    2006-04-01

    In the present study, the effects of maternal swimming during pregnancy on the short-term memory ability, hippocampal neurogenesis, and brain-derived neurotrophic factor (BDNF) mRNA expression of rat pups were investigated. After confirming their pregnancy, the pregnant rats were divided into two groups: the control group and the swimming group. From the 15th day of pregnancy until delivery, pregnant rats were subcutaneously injected with 100mg/kg of 5-bromo-2'-deoxyuridine (BrdU) once a day at 30min before the starting of swimming exercise. Pregnant rats in the swimming group were forced to swim for 10min once a day until delivery. On the 21 days after birth, the rat pups were trained in a step-down avoidance test. The latency time of the step-down avoidance task was determined on the 28 days after birth in order to evaluate the short-term memory ability of pups. On the 29 days after birth, the rat pups' brains were removed, and BrdU immunohistochemistry for the detection of neurogenesis and reverse transcription-polymerase chain reaction (RT-PCR) for the detection of BDNF mRNA expression were then performed. The rat pups born from the maternal rats that performed swimming during pregnancy showed significantly increased BDNF mRNA expression, enhanced hippocampal neurogenesis, and improved short-term memory capability. The present results have clearly shown that maternal swimming by rats during pregnancy enhances the memory of the rats' offspring by increasing neurogenesis. Our present study provides the evidence that maternal exercise during the gestational period may enhance the brain functions of the mothers' offspring.

  9. Maternal Disononyl Phthalate Exposure Activates Allergic Airway Inflammation via Stimulatingthe Phosphoinositide 3-kinase/Akt Pathway in Rat Pups

    Institute of Scientific and Technical Information of China (English)

    CHEN Li; CHEN Jiao; XIE ChangMing; ZHAO Yan; WANG Xiu; andZHANG YunHui

    2015-01-01

    ObjectiveTo evaluate the effectof diisononyl phthalate (DINP) exposure during gestation and lacta-tion on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. MethodsFemale Wistar rats were treated with DINP at different dosages (0, 5, 50,and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin (OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin (HE) staining; and the relative cytokines in phosphoinositide 3-kinase (PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. ResultsThere was no significant difference in DINP’s effect on airway hyperresponsiveness (AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance (RI) compared with those from controls (P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed. ConclusionTherewas an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.

  10. Maternal milk, but not formula, regulates the immune response to beta-lactoglobulin in allergy-prone rat pups.

    Science.gov (United States)

    Tooley, Katie L; El-Merhibi, Adaweyah; Cummins, Adrian G; Grose, Randall H; Lymn, Kerry A; DeNichilo, Mark; Penttila, Irmeli A

    2009-11-01

    Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to beta-lactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, or 21. Sera were assayed for total IgE, BLG-specific IgG1, and rat mucosal mast cell protease II (RMCPII; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 (CCR7) expression by real-time PCR and immunostained for Foxp3(+) CD4(+) regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1, RMCPII, and intestinal mast cells but reduced MLN Foxp3(+) cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (IL)-4, IL-10, and interferon-gamma (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and CD4(+) Foxp3(+) cells (P < 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response.

  11. Erythropoietin improved cognitive function and decreased hippocampal caspase activity in rat pups after traumatic brain injury.

    Science.gov (United States)

    Schober, Michelle E; Requena, Daniela F; Block, Benjamin; Davis, Lizeth J; Rodesch, Christopher; Casper, T Charles; Juul, Sandra E; Kesner, Raymond P; Lane, Robert H

    2014-02-15

    Traumatic brain injury (TBI) is a leading cause of acquired neurologic disability in children. Erythropoietin (EPO), an anti-apoptotic cytokine, improved cognitive outcome in adult rats after TBI. To our knowledge, EPO has not been studied in a developmental TBI model. We hypothesized that EPO would improve cognitive outcome and increase neuron fraction in the hippocampus in 17-day-old (P17) rat pups after controlled cortical impact (CCI). EPO or vehicle was given at 1, 24, and 48 h after CCI and at post injury day (PID) 7. Cognitive outcome at PID14 was assessed using Novel Object Recognition (NOR). Hippocampal EPO levels, caspase activity, and mRNA levels of the apoptosis factors Bcl2, Bax, Bcl-xL, and Bad were measured during the first 14 days after injury. Neuron fraction and caspase activation in CA1, CA3, and DG were studied at PID2. EPO normalized recognition memory after CCI. EPO blunted the increased hippocampal caspase activity induced by CCI at PID1, but not at PID2. EPO increased neuron fraction in CA3 at PID2. Brain levels of exogenous EPO appeared low relative to endogenous. Timing of EPO administration was associated with temporal changes in hippocampal mRNA levels of EPO and pro-apoptotic factors. Conclusion/Speculation: EPO improved recognition memory, increased regional hippocampal neuron fraction, and decreased caspase activity in P17 rats after CCI. We speculate that EPO improved cognitive outcome in rat pups after CCI as a result of improved neuronal survival via inhibition of caspase-dependent apoptosis early after injury.

  12. Sex differences in heart rate variability during sleep following prenatal nicotine exposure in rat pups.

    Science.gov (United States)

    Boychuk, Carie R; Fuller, David D; Hayward, Linda F

    2011-05-16

    The influence of both prenatal nicotine exposure (PNE; 6 mg/kg/day) and sex on heart rate (HR) regulation during sleep versus wakefulness was evaluated in 13, 16 and 26 day old rat pups. Pups were chronically instrumented at least 24 h before testing. On postnatal day 13 (P13), PNE males spent significantly more time in NREM sleep and demonstrated a greater drop in HR when transitioning from quiet wake to sleep compared to age and sex matched controls (-14±5 bpm versus -1±3 bpm, respectively). Heart rate variability (HRV) analysis indicated that this state-dependent drop in HR was primarily associated with a greater reduction in sympathovagal balance (LF/HF ratio) in PNE males compared to controls. No parallel changes in indices of parasympathetic drive (HF power) were identified. In contrast, no significant effect of PNE on HR during sleep versus wakefulness was identified in P13 females. However, independent of state, a significant decrease in HF power was identified in P13 PNE females compared to controls. At P16, state-dependent differences in HR or HRV between PNE and sex-matched control pups were resolved. Additionally, at P26 no significant effect of PNE on state-dependent changes in HR or HRV was identified in either sex. Analysis of the hypothalamic peptide orexin identified that PNE induced approximately a 50% reduction in hypothalamic prepro-orexin mRNA and total mRNA was lowest in PNE males. These findings suggest that PNE induces sex dependent changes in sleep related autonomic regulation of HR during early postnatal development and these changes may be related to epigenetic alterations in the orexin system.

  13. Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

    Science.gov (United States)

    Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

    2015-09-08

    Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Effects of iron supplementation on growth, gut microbiota, metabolomics and cognitive development of rat pups.

    Science.gov (United States)

    Alexeev, Erica E; He, Xuan; Slupsky, Carolyn M; Lönnerdal, Bo

    2017-01-01

    Iron deficiency is common during infancy and therefore iron supplementation is recommended. Recent reports suggest that iron supplementation in already iron replete infants may adversely affect growth, cognitive development, and morbidity. Normal and growth restricted rat pups were given iron daily (30 or 150 μg/d) from birth to postnatal day (PD) 20, and followed to PD56. At PD20, hematology, tissue iron, and the hepatic metabolome were measured. The plasma metabolome and colonic microbial ecology were assessed at PD20 and PD56. T-maze (PD35) and passive avoidance (PD40) tests were used to evaluate cognitive development. Iron supplementation increased iron status in a dose-dependent manner in both groups, but no significant effect of iron on growth was observed. Passive avoidance was significantly lower only in normal rats given high iron compared with controls. In plasma and liver of normal and growth-restricted rats, excess iron increased 3-hydroxybutyrate and decreased several amino acids, urea and myo-inositol. While a profound difference in gut microbiota of normal and growth-restricted rats was observed, with iron supplementation differences in the abundance of strict anaerobes were observed. Excess iron adversely affects cognitive development, which may be a consequence of altered metabolism and/or shifts in gut microbiota.

  15. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  16. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  17. Development of motor coordination and cerebellar structure in male and female rat neonates exposed to hypergravity

    Science.gov (United States)

    Nguon, K.; Ladd, B.; Baxter, M. G.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that the developing rat cerebellum is affected by exposure to hypergravity. In the present study, we explored the hypothesis that the changes in cerebellar structure in hypergravity-exposed rat neonates may affect their motor coordination. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravitational loading. To test this hypothesis, we compared motor behavior, cerebellar structure, and protein expression in rat neonates exposed to 1.5 1.75G on a 24-ft centrifuge daily for 22.5 h starting on gestational day (G) 10, through birth on G22/G23 and through postnatal day (P) 21. Exposure to hypergravity impacted the neurodevelopmental process as indicated by: (1) impaired righting response on P3, more than doubling the righting time at 1.75G, and (2) delayed onset of the startle response by one day, from P9 in controls to P10 in hypergravity-exposed pups. Hypergravity exposure resulted in impaired motor functions as evidenced by performance on a rotarod on P21; the duration of the stay on the rotarod recorded for 1.75G pups of both sexes was one tenth that of the stationary control (SC) pups. These changes in motor behavior were associated with cerebellar changes: (1) cerebellar mass on P6 was decreased by 7.5% in 1.5G-exposed male pups, 27.5% in 1.75G-exposed male pups, 17.5% in 1.5G-exposed female pups, and 22.5% in 1.75G female pups and (2) changes in the expression of glial and neuronal proteins. The results of this study suggest that perinatal exposure to hypergravity affects cerebellar development as evidenced by decreased cerebellar mass and altered cerebellar protein expression; cerebellar changes observed in hypergravity-exposed rat neonates are associated with impaired motor behavior. Furthermore, the response to hypergravity appears to be different in male and female neonates. If one accepts that the hypergravity paradigm is a useful animal model with which to predict those biological processes

  18. Reduction in ultrasonic vocalizations in pups born to rapid eye movement sleep restricted mothers in rat model.

    Directory of Open Access Journals (Sweden)

    Kamalesh K Gulia

    Full Text Available The effects of rapid eye movement sleep restriction (REMSR in rats during late pregnancy were studied on the ultrasonic vocalizations (USVs made by the pups. USVs are distress calls inaudible to human ears. Rapid eye movement (REM sleep was restricted in one group of pregnant rats for 22 hours, starting from gestational day 14 to 20, using standard single platform method. The USVs of male pups were recorded after a brief isolation from their mother for two minutes on alternate post-natal days, from day one till weaning. The USVs were recorded using microphones and were analysed qualitatively and quantitatively using SASPro software. Control pups produced maximum vocalization on post-natal days 9 to 11. In comparison, the pups born to REMSR mothers showed not only a reduction in vocalization but also a delay in peak call making days. The experimental group showed variations in the types and characteristics of call types, and alteration in temporal profile. The blunting of distress call making response in these pups indicates that maternal sleep plays a role in regulating the neural development involved in vocalizations and possibly in shaping the emotional behaviour in neonates. It is suggested that the reduced ultrasonic vocalizations can be utilized as a reliable early marker for affective state in rat pups. Such impaired vocalization responses could provide an important lead in understanding mother-child bonding for an optimal cognitive development during post-partum life. This is the first report showing a potential link between maternal REM sleep deprivation and the vocalization in neonates and infants.

  19. Firing patterns of maternal rat prelimbic neurons during spontaneous contact with pups.

    Science.gov (United States)

    Febo, Marcelo

    2012-08-01

    Extracellular single unit activity was recorded from medial prefrontal cortex (mPFC) of postpartum dams over the course of 3 days while they engaged in spontaneous pup-directed behaviors and non-specific exploratory behavior. Out of 109 units identified over the course of the experiment, 15 units were observed to be pup-responsive and 15 increased their discharge rates non-specifically while not attending to pups. An association between neuronal activity and typical maternal behaviors (e.g., retrieval, pup-grooming, nursing) was not observed. Instead, brief bouts of snout contact with pups were accompanied by phasic increases and decreases in spike rates. The observed pup contact responsive cells might play a role in processing of sensory feedback from pups or the transmission of modulatory output to other subcortical maternal brain areas.

  20. Ameliorative effect of Morus alba leaves extract against developmental retinopathy in pups of diabetic and aluminum intoxicated pregnant albino rats

    Institute of Scientific and Technical Information of China (English)

    Hassan; El-Sayyed; Gamal; Badawy; Sobhy; Hassab; Elnabi; Ibrahim; El-Elaimy; Eman; Al; Shehari

    2015-01-01

    Objective: To investigate the possible ameliorative effect of crude water extract of Morus alba(M. alba) leaves on retinopathy of rat pups maternally subjected to diabetes and/or Al intoxication.Methods: Both control and experimental groups were subjected to certain integrated approaches, namely, biochemical assessments, light microscopic investigation, transmission electron microscopic investigation, single cell gel electrophoresis(comet assay) and determination of DNA fragmentation.Results: The retina of pups of diabetic and/or Al-intoxicated mothers exhibited abnormal alterations in retinal cell layers including retinal pigmented epithelium, photoreceptor inner segment and ganglion cells. Increased incidence of DNA fragmentation and apoptosis were evident in pups of diabetic and/or Al-intoxicated mothers. However, retina of pups maternally received M. alba extract plus diabetes or Al-intoxicated alone or in combination showed marked amelioration. Less degree of ameliorations was seen in retina of pups maternally subjected to combined treatment. Furthermore, application of crude water extract of M.alba resulted in amelioration of the alterations of maternal serum glucose as well as Al concentration.Conclusions: Based on the results of the present study, M. alba extract is effective against experimentally diabetic and Al-induced developmental retinopathy.

  1. Effects of intra-uterine and early extra-uterine malnutrition on seizure threshold and hippocampal morphometry of pup rats.

    Science.gov (United States)

    Florian, Mariana Lorenzet; Nunes, Magda Lahorgue

    2010-12-01

    We evaluate the influence of different malnutrition paradigms (intra-uterine × extra-uterine) in body and brain weight, in seizure threshold and in hippocampus morphometry, in developing rats. Intra-uterine malnutrition model consisted in reduction by half of the ration offered to pregnant female; extra-uterine malnutrition consisted of progressive limitation of lactation, from P2 to P15. Seizure induction was accomplished by exposure to flurothyl, at P15. At the same day animals were sacrificed. Morphometric analysis was based on hippocampal pyramidal and granular cells estimate number, through volume calculation and cellular density. Extra-uterine malnutrition significantly reduced pups body and brain weight, seizure threshold and neuronal number in CA4 region only. Intra-uterine malnutrition reduced neuronal number in CA2, CA4 and DG regions regarding well-nourished and extra-uterine malnourished animals. In CA3, CA4 and dentate gyrus, a significant cell increase was observed in groups exposed to seizures, regarding similar control groups.

  2. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    OpenAIRE

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat p...

  3. FIRING PATTERNS OF MATERNAL RAT PRELIMBIC NEURONS DURING SPONTANEOUS CONTACT WITH PUPS

    OpenAIRE

    Febo, Marcelo

    2012-01-01

    Extracellular single unit activity was recorded from medial prefrontal cortex (mPFC) of postpartum dams over the course of 3 days while they engaged in spontaneous pup-directed behaviors and non-specific exploratory behavior. Out of 109 units identified over the course of the experiment, 15 units were observed to be pup-responsive and 15 increased their discharge rates non-specifically while not attending to pups. An association between neuronal activity and typical maternal behaviors (e.g., ...

  4. Chronic Early-life Stress in Rat Pups Alters Basal Corticosterone, Intestinal Permeability, and Fecal Microbiota at Weaning: Influence of Sex.

    Science.gov (United States)

    Moussaoui, Nabila; Jacobs, Jonathan P; Larauche, Muriel; Biraud, Mandy; Million, Mulugeta; Mayer, Emeran; Taché, Yvette

    2017-01-30

    Wistar rat dams exposed to limited nesting stress (LNS) from post-natal days (PND) 2 to 10 display erratic maternal behavior, and their pups show delayed maturation of the hypothalamic-pituitary-adrenal axis and impaired epithelial barrier at PND10 and a visceral hypersensitivity at adulthood. Little is known about the impact of early life stress on the offspring before adulthood and the influence of sex. We investigated whether male and female rats previously exposed to LNS displays at weaning altered corticosterone, intestinal permeability, and microbiota. Wistar rat dams and litters were maintained from PND2 to 10 with limited nesting/bedding materials and thereafter reverted to normal housing up to weaning (PND21). Control litters had normal housing. At weaning, we monitored body weight, corticosterone plasma levels (enzyme immunoassay), in vivo intestinal to colon permeability (fluorescein isothiocyanate-dextran 4 kDa) and fecal microbiota (DNA extraction and amplification of the V4 region of the 16S ribosomal RNA gene). At weaning, LNS pups had hypercorticosteronemia and enhanced intestinal permeability with females > males while body weights were similar. LNS decreased fecal microbial diversity and induced a distinct composition characterized by increased abundance of Gram positive cocci and reduction of fiber-degrading, butyrate-producing, and mucus-resident microbes. These data indicate that chronic exposure to LNS during the first week post-natally has sustained effects monitored at weaning including hypercorticosteronemia, a leaky gut, and dysbiosis. These alterations may impact on the susceptibility to develop visceral hypersensitivity in adult rats and have relevance to the development of irritable bowel syndrome in childhood.

  5. Chronic Early-life Stress in Rat Pups Alters Basal Corticosterone, Intestinal Permeability, and Fecal Microbiota at Weaning: Influence of Sex

    Science.gov (United States)

    Moussaoui, Nabila; Jacobs, Jonathan P; Larauche, Muriel; Biraud, Mandy; Million, Mulugeta; Mayer, Emeran; Taché, Yvette

    2017-01-01

    Background/Aims Wistar rat dams exposed to limited nesting stress (LNS) from post-natal days (PND) 2 to 10 display erratic maternal behavior, and their pups show delayed maturation of the hypothalamic-pituitary-adrenal axis and impaired epithelial barrier at PND10 and a visceral hypersensitivity at adulthood. Little is known about the impact of early life stress on the offspring before adulthood and the influence of sex. We investigated whether male and female rats previously exposed to LNS displays at weaning altered corticosterone, intestinal permeability, and microbiota. Methods Wistar rat dams and litters were maintained from PND2 to 10 with limited nesting/bedding materials and thereafter reverted to normal housing up to weaning (PND21). Control litters had normal housing. At weaning, we monitored body weight, corticosterone plasma levels (enzyme immunoassay), in vivo intestinal to colon permeability (fluorescein isothiocyanate-dextran 4 kDa) and fecal microbiota (DNA extraction and amplification of the V4 region of the 16S ribosomal RNA gene). Results At weaning, LNS pups had hypercorticosteronemia and enhanced intestinal permeability with females > males while body weights were similar. LNS decreased fecal microbial diversity and induced a distinct composition characterized by increased abundance of Gram positive cocci and reduction of fiber-degrading, butyrate-producing, and mucus-resident microbes. Conclusions These data indicate that chronic exposure to LNS during the first week post-natally has sustained effects monitored at weaning including hypercorticosteronemia, a leaky gut, and dysbiosis. These alterations may impact on the susceptibility to develop visceral hypersensitivity in adult rats and have relevance to the development of irritable bowel syndrome in childhood. PMID:27829577

  6. Early-life stress is associated with gender-based vulnerability to epileptogenesis in rat pups.

    Directory of Open Access Journals (Sweden)

    Sébastien Desgent

    Full Text Available During development, the risk of developing mesial temporal lobe epilepsy (MTLE increases when the developing brain is exposed to more than one insult in early life. Early life insults include abnormalities of cortical development, hypoxic-ischemic injury and prolonged febrile seizures. To study epileptogenesis, we have developed a two-hit model of MTLE characterized by two early-life insults: a freeze lesion-induced cortical malformation at post-natal day 1 (P1, and a prolonged hyperthermic seizure (HS at P10. As early life stressors lead to sexual dimorphism in both acute response and long-term outcome, we hypothesized that our model could lead to gender-based differences in acute stress response and long-term risk of developing MTLE. Male and female pups underwent a freeze-lesion induced cortical microgyrus at P1 and were exposed to HS at P10. Animals were monitored by video-EEG from P90 to P120. Pre and post-procedure plasma corticosterone levels were used to measure stress response at P1 and P10. To confirm the role of sex steroids, androgenized female pups received daily testosterone injections to the mother pre-natally and post-natally for nine days while undergoing both insults. We demonstrated that after both insults females did not develop MTLE while all males did. This correlated with a rise in corticosterone levels at P1 following the lesion in males only. Interestingly, all androgenized females showed a similar rise in corticosterone at P1, and also developed MTLE. Moreover, we found that the cortical lesion significantly decreased the latency to generalized convulsion during hyperthermia at P10 in both genders. The cortical dysplasia volumes at adulthood were also similar between male and female individuals. Our data demonstrate sexual dimorphism in long-term vulnerability to develop epilepsy in the lesion + hyperthermia animal model of MTLE and suggest that the response to early-life stress at P1 contributes significantly to

  7. Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development

    Institute of Scientific and Technical Information of China (English)

    LI Chen Xi; MA Chuan; FANG Hai Qin; ZHI Yuan; YU Zhou; XU Hai Bin; JIA Xu Dong

    2015-01-01

    Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21;however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.

  8. The effect of methylxanthines on milk volume and composition, and growth of rat pups.

    Science.gov (United States)

    Hart, A D; Grimble, R F

    1990-09-01

    A study was conducted to investigate the effect of differential dose levels of methylxanthines on lactational performance, with respect to milk volume and composition and pup growth. The methylxanthines; caffeine, theophylline and theobromine, were administered via drinking water in the proportions occurring in tea, at a dose of 50, 1 and 2 mg/kg body-weight respectively to Wistar albino rats throughout pregnancy and for up to the 14th day of lactation. A fourth group received a mixture of all three methylxanthines. Maternal food and fluid intake and weight changes, as well as weight gain in the litter were monitored thrice weekly. Milk samples were collected from the dams on days 7 and 14 of lactation, while milk volume was measured on days 12-13 by a method using tritiated water. Results showed that caffeine and theobromine significantly enhanced litter weight (P less than 0.01 and 0.05 respectively). In the caffeine group, enhanced litter growth was due to a significant increase (P less than 0.05) in milk volume, consequent to increased maternal food intake (P less than 0.05). In the theobromine group there was only a weak association between increased litter weight and milk volume. Theophylline had no effect on the volume or composition of milk, or litter weight. The combination of all three methylxanthines also failed to produce any of the positive effects observed with separate drug treatments.

  9. Dabigatran ameliorates post-haemorrhagic hydrocephalus development after germinal matrix haemorrhage in neonatal rat pups.

    Science.gov (United States)

    Klebe, Damon; Flores, Jerry J; McBride, Devin W; Krafft, Paul R; Rolland, William B; Lekic, Tim; Zhang, John H

    2016-01-01

    We aim to determine if direct thrombin inhibition by dabigatran will improve long-term brain morphological and neurofunctional outcomes and if potential therapeutic effects are dependent upon reduced PAR-1 stimulation and consequent mTOR activation. Germinal matrix haemorrhage was induced by stereotaxically injecting 0.3 U type VII-S collagenase into the germinal matrix of P7 rat pups. Animals were divided into five groups: sham, vehicle (5% DMSO), dabigatran intraperitoneal, dabigatran intraperitoneal + TFLLR-NH2 (PAR-1 agonist) intranasal, SCH79797 (PAR-1 antagonist) intraperitoneal, and dabigatran intranasal. Neurofunctional outcomes were determined by Morris water maze, rotarod, and foot fault evaluations at three weeks. Brain morphological outcomes were determined by histological Nissl staining at four weeks. Expression levels of p-mTOR/p-p70s6k at three days and vitronectin/fibronectin at 28 days were quantified. Intranasal and intraperitoneal dabigatran promoted long-term neurofunctional recovery, improved brain morphological outcomes, and reduced intracranial pressure at four weeks after GMH. PAR-1 stimulation tended to reverse dabigatran's effects on post-haemorrhagic hydrocephalus development. Dabigatran also reduced expression of short-term p-mTOR and long-term extracellular matrix proteins, which tended to be reversed by PAR-1 agonist co-administration. PAR-1 inhibition alone, however, did not achieve the same therapeutic effects as dabigatran administration.

  10. Effect of treating lactating rats with lead acetate and its interaction with vitamin E or C on neurobehavior, development and some biochemical parameters in their pups

    Directory of Open Access Journals (Sweden)

    A. A. Hassan

    2010-01-01

    Full Text Available The current study investigated the effect of administration of vitamin E (600mg/ kg diet concomitantly with lead acetate (10mg/kg, orally and vitamin C (100mg/kg, orally concomitantly with lead acetate (10mg/kg, orally to the female lactating rats on the neurobehavioral, landmarks development and some biochemical tests in their pups. Administration of lead acetate to the female lactating rats caused a significant increase in open field activity test including (the number of squares crossed and rearing test within 3 minutes, olfactory discrimination test, triglycerides and malondialdehyde brain tissue, with a significant decrease in glutathione brain tissue and high density lipoproteins in their pups. The present study demonstrated that treatment of female lactating rats with vitamin C and lead acetate produced a significant decrease in righting reflex test in their pups. Administration of vitamin E concomitantly with lead acetate to the female lactating rats caused a significant increase in glutathione level accompanied with a significant decrease in malondialdehyde and triglycerides levels in their pups. The present study showed that treatment of female lactating rats with vitamin E or C with lead acetate produced a significant decrease in rearing test, whereas a significant increase in high density lipoproteins in their pups. It is concluded that administration vitamin E or C to the female lactating rats reverse the adverse effects produced by lead acetate on neurobehavioral. Vitamin E had positive effect on the levels of glutathione, malondialdehyde brain tissue, triglyceride and high density lipoproteins in their lactating pups.

  11. Maternal behavior priming in virgin and caesarean-delivered Long-Evans rats: effects of brief contact or continuous exteroceptive pup stimulation.

    Science.gov (United States)

    Stern, J M

    1983-12-01

    The effects of 8 days of prior exposure to pups (Priming) in the form of continuous exteroceptive (smell, sight and sound), or 15 min/day physical access (taste and touch possible) stimulation on the subsequent latency to become maternal during cohabitation with pups (concaveation) was studied in Long-Evans female rats. Brief daily access was effective in hastening the onset of maternal behavior only in those virgins which engaged in pup licking during Priming and in maintaining short-latency maternal responsiveness only in those day 21 pregnancy-terminated, thelectomized rats which initiated maternal behavior during Priming. Exteroceptive stimulation was ineffective in both virgins and caesarean-sectioned rats. These findings stress the importance of physical interactions with pups (unrelated to nipple stimulation) for the development of nurturance.

  12. Protective Effects of Morus alba Leaves Extract on Ocular Functions of Pups from Diabetic and Hypercholesterolemic Mother Rats

    Directory of Open Access Journals (Sweden)

    H.I.H. El-Sayyad, M.A. El-Sherbiny, M.A. Sobh, A.M. Abou-El-Naga, M.A.N. Ibrahim, S.A. Mousa

    2011-01-01

    Full Text Available Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE, adrenaline (AD, nor-adrenaline (NAD, serotonin (5-HT, histamine (HS, dopamine (DA and gamma amino butyric acid (GABA. The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.

  13. cerebellar parameters in developing 15 day old rat pups treated with ...

    African Journals Online (AJOL)

    2001-06-06

    Jun 6, 2001 ... numbers of neurons and Purkinje cells in intracerebellar nuclei and cerebellum respectively ... numerical density and total number of glial cells in treated pups ... Cerebellar parameters in the same, showed significant.

  14. Effects of voluntary exercise on the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups born from morphine- dependent mothers during pregnancy.

    Science.gov (United States)

    Haydari, Sakineh; Safari, Manouchehr; Zarbakhsh, Sam; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

    2016-11-10

    This study was designed to investigate whether free access to a running wheel during pregnancy in morphine-dependent mothers would influence the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with free access to a running wheel. Male pups are weaned at 21days of birth and their bones marrows were aspirated from the femurs and tibias and also the bone marrow stromal cells (BMSCs) cultured. MTT assay was used to determine cell viability and proliferation rate. The level of BDNF was measured in the supernant of BMSCs culture by ELISA. The sedentary morphine-dependent mothers' pups showed a significant increase in the percentage cell viability and proliferation rate and also a significant decrease in the BDNF protein levels in BMSCs. The rat pups borne from exercising the control and morphine-dependent mothers exhibited an increase in the percentage viability, proliferation rate and BDNF levels of the BMSCs. This study showed that maternal exercise during pregnancy in morphine-dependent and non-dependent mothers, with increasing of BDNF levels increased the proliferation and viability of BMSCs in the rat pups. Also, chronic administration of morphine during pregnancy was able to increase the proliferation and viability of BMSCs in the rat pups. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Serotonin transporter occupancy in rats exposed to serotonin reuptake inhibitors in utero or via breast milk.

    Science.gov (United States)

    Capello, Catherine F; Bourke, Chase H; Ritchie, James C; Stowe, Zachary N; Newport, D Jeffrey; Nemeroff, Amanda; Owens, Michael J

    2011-10-01

    Rigorous data regarding fetal central nervous system (CNS) exposure after antidepressant exposure are sparse. The magnitude of serotonin reuptake inhibitor (SRI) CNS exposure was measured in three groups of rats using ex vivo autoradiography of the serotonin transporter (SERT): 1) in utero, 2) postnatal clearance after birth, and 3) exposure through lactation. Rats were exposed to one of five SRI-type antidepressants (escitalopram, fluoxetine, paroxetine, sertraline, and venlafaxine) administered continuously via osmotic minipumps to pregnant or nursing dams. Dam dosing was adjusted to reflect the 50th and 85th percentiles of serum concentrations observed in pregnant women. Embryonic day 21 rat pups exposed in utero exhibited >80% SERT occupancy in brain tissue, which is equivalent to that of the pregnant dam and similar to that reported for human pharmacotherapy. Venlafaxine was the exception with occupancies ranging from 61 to 92% across different litters. The magnitude of SERT occupancy is essentially equivalent between dams and fetuses. By postnatal day 4, high SERT occupancy was observed only in fluoxetine-exposed pups (41-92% occupancy). Significantly less, but measurable, exposure occurred via breast milk exposure even in the absence of detectable drug concentrations in nursing pup sera. Pups exposed to SRIs via breast milk for 3 or 7 days exhibited varying SERT occupancies (0-57% depending on the individual medication and dam dose). These data highlight the need for animal modeling of fetal and nursing infant drug exposure using clinically meaningful dosing strategies and appropriate CNS measures to develop rational treatment guidelines that systematically minimize fetal and neonatal medication exposure in humans.

  16. Enriched environment restricted to gestation accelerates the development of sensory and motor circuits in the rat pup.

    Science.gov (United States)

    Cárdenas, Lorena; García-García, Fabio; Santiago-Roque, Isela; Martínez, Armando J; Coria-Ávila, Genaro A; Corona-Morales, Aleph A

    2015-04-01

    The effects of stimulating environments on the neural plasticity of the adult brain have been well explored; however, how an enriched environment (EE) affects the mother-fetus interaction is poorly understood. We hypothesized that an enriched environment restricted to pregnancy will succeed in accelerating the development of sensory and motor circuits in the offspring. Pregnant Wistar rats were maintained either under a standard condition - two animals per standard cage- or an enriched environment - eight subjects in larger cages with different physical configurations-. After birth, litters from both groups (n=16 per group) were cross-fostered with mothers that were simultaneously maintained under standard environment during pregnancy. Sensory and motor development were studied in the pups of both groups with a battery of reflex and physical tests. Auditory and gait reflexes appeared two days earlier in the offspring of EE rats as compared to control subjects (p<0.05). In addition, EE pups displayed a better performance in righting reflex, inclined board and geotaxis tests (p<0.05). Differences were found even three weeks after birth. We conclude that EE limited to the phase of pregnancy stimulates the development of pups inutero so that they are born with a higher grade of development.

  17. Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise.

    Science.gov (United States)

    Shafiee, Seyed Morteza; Vafaei, Abbas Ali; Rashidy-Pour, Ali

    2016-08-01

    Hypothyroidism during early development leads to numerous morphological, biochemical and functional changes in developing brain. In this study, we investigated the effects of voluntary and treadmill exercise on learning, memory and hippocampal BDNF levels in both hypothyroid male and female rat pups. To induce hypothyroidism in the mothers, 6-propyl-2-thiouracil (PTU) was added to their drinking water (100mg/L) from their embryonic day 6 to their postnatal day (PND) 21. For 14days, from PNDs 31 to 44, the rat pups were trained with one of the two different exercise protocols, namely the mild treadmill exercise and the voluntary wheel exercise. On PNDs 45-52, a water maze was used for testing their learning and memory ability. The rats were sacrificed one day later and their BDNF levels were then measured in the hippocampus. The findings of the present study indicate that hypothyroidism during the fetal period and the early postnatal period is associated with the impairment of spatial learning and memory and reduced hippocampal BDNF levels in both male and female rat offspring. Both the short-term treadmill exercise and the voluntary wheel exercise performed during the postnatal period reverse the behavioral and neurochemical deficits induced by developmental thyroid hormone insufficiency in both male and female rat offspring. The findings of this study thus demonstrate a marked reversibility of both behavioral and neurochemical disorders induced by developmental thyroid hormone insufficiency through the performance of exercise.

  18. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

    Science.gov (United States)

    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

  19. Neuropathies of spinal cord development in rat pups maternally fed with fried potato chips

    Directory of Open Access Journals (Sweden)

    Abdelalim A. Gad-Allah

    2013-08-01

    Results: Comparing with acrylamide-treatment, protein expression in spinal cord of pups maternally fed with fried potatoes was altered. Necrosis of motor neuronal cells within grey matter, hyperplasia of ependymal lining cells and fragility of white matter was detected. At ultrastructural level, the sensory and motor neuronal cells showed convoluted nuclear envelope and either chromatolysis or compacted chromatin material. Fragmentation of rough endoplasmic reticulum and damage of mitochondria become well evident in pups maternally fed with potato chips. The neuronal axons possessed vacuolation and demyelination associated with apparent damage of mitochondria. Conclusion: Supplementation of fried potato chips exerted neurotoxicity either directly through their content of acrylamide or via its metabolite glycidamide. Both components were reported to find their way across the placenta during gestation and breast milk during the lactation period, interfering with spinal cord differentiation and adversely affected demyelination. [J Exp Integr Med 2013; 3(4.000: 285-292

  20. Combined exposure to endocrine disrupting pesticides impairs parturition and causes pup mortality in rats

    DEFF Research Database (Denmark)

    Hansen, Pernille Reimer; Christiansen, Sofie; Boberg, Julie

    Risk assessment is currently based on the no observed adverse effect level (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and epidemiological studies have reported some associations between endocrine disrupting effects and combined exposure to certain pesticides....... Although laboratory animal studies have shown that some endocrine disrupting pesticides can affect reproduction and sexual differentiation, individual pesticides may appear to be present in human tissues at too low levels to cause concern for adverse reproductive effects. However, recent studies in our...... to five pesticides, i.e. procymidone, mancozeb, tebuconazole, epoxiconazole and prochloraz. Common features for the three azole fungicides are that they increase gestational length possibly because of an increase in progesterone levels in dams. Groups of 8 time-mated Wistar rats (HanTac:WH) were gavaged...

  1. Effects of voluntary exercise on anxiety-like behavior and voluntary morphine consumption in rat pups borne from morphine-dependent mothers during pregnancy.

    Science.gov (United States)

    Haydari, Sakineh; Miladi-Gorji, Hossein; Mokhtari, Amin; Safari, Manouchehr

    2014-08-22

    Exposure to morphine during pregnancy produced long-term effects in offspring behaviors. Recent studies have shown that voluntary exercise decreases the severity of anxiety behaviors in both morphine-dependent and withdrawn rats. Thus, the aims of the present study were to examine whether maternal exercise decreases prenatal dependence-induced anxiety and also, voluntary consumption of morphine in animal models of craving in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with access to a running wheel that lasted at least 21 days. Then, anxiety-like behaviors using the elevated plus-maze (EPM) and voluntary consumption of morphine using a two-bottle choice paradigm (TBC) were tested in male rat pups. The results showed that the rat pups borne from exercising morphine-dependent mothers exhibited an increase in EPM open arm time (Pexercising morphine-dependent mothers was less in the second (Pexercise decreases the severity of the anxiogenic-like behaviors and voluntary consumption of morphine in rat pups.

  2. Prenatal Curcumin Administration Reverses Behavioral and Neurochemical Effects and Decreases iNOS and COX-2 Expressions in Ischemic Rat Pups

    Directory of Open Access Journals (Sweden)

    Maria Valéria Leimig Telles

    2014-01-01

    Full Text Available The objectives were to evaluate alterations in ischemic rat pups, from dams administered with curcumin (25 and 50 mg/kg. Ten-day-old male pups were subjected or not (SO to brain ischemia and reperfusion, for 1, 7, and 14 days (this last group was submitted to behavioral evaluation. After that, pups were euthanized for determinations of striatal DA and DOPAC in SO, ischemic from untreated (ICUD or curcumin treated (ICTD dams, as well as hippocampal immunohistochemistry assays for iNOS and COX-2 and cresyl violet staining. At the 14th postischemia day, the ICUD group showed increased locomotor activity and rearing behavior, which were reversed in ICTD animals. ICUD pups presented decreased striatal DA and DOPAC levels, relatively to SO, mainly at the 1st postischemia day, but also at the 7th and 14th days which were partially reversed in ICTD pups. A greater number of viable neurons were observed in ICTD, as related to the ICUD group. Ischemia increased iNOS and COX-2 expressions, in CA1 and CA3 areas, at the 1st, 7th, and 14th postischemia days, and these effects were minimized in ICTD pups. In conclusion, the prenatal curcumin treatment was shown to be neuroprotective where the drug anti-inflammatory and antioxidant effects probably play a role.

  3. Neonatal handling and the maternal odor preference in rat pups: involvement of monoamines and cyclic AMP response element-binding protein pathway in the olfactory bulb.

    Science.gov (United States)

    Raineki, C; De Souza, M A; Szawka, R E; Lutz, M L; De Vasconcellos, L F T; Sanvitto, G L; Izquierdo, I; Bevilaqua, L R; Cammarota, M; Lucion, A B

    2009-03-03

    Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age.

  4. Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and kidneys of lactating mother rats and their pups'.

    Science.gov (United States)

    Mahmoudi, Asma; Ghorbel, Héla; Bouallegui, Zouhair; Marrekchi, Rim; Isoda, Hiroko; Sayadi, Sami

    2015-01-01

    Bisphenol A (BPA) is a chemical found in hard plastics and the coatings of food and drinks cans which can behave in a similar way to estrogen and other hormones in the human body. This study aimed to evaluate the significance of the treatment with oleuropein and hydroxytyrosol olive leaves rich extracts in reducing functional perturbations and oxidative stress arising from BPA treatment in livers and kidneys of lactating mother rats and their pups'. For this, four groups of lactating mothers were used: controls (group A), treated with bisphenol A (group B), treated with bisphenol A and oleuropein (group C) and with bisphenol A and hydroxytyrosol (group D). As results, we had found, in BPA treated group, either in mothers or in their pups', a significant decrease in morphological parameters, in catalase activity and in total antioxidant capacity associated to an increase in malondialdehyde levels in livers and kidneys. For these rats, the histological aspect showed, also, deep changes. Indeed, we had observed, in livers, hepatocellular necrosis associated to leucocytes infiltration and in kidneys tubular and glomerular necrosis. The co-treatments with BPA and oleuropein (group C) or with BPA and hydroxytyrosol (group D) ameliorate all morphological, biochemical and histological parameters as compared to BPA treated group B. The analysis of BPA and its derivatives with LC-MS/MS showed changes in their localizations between serum, livers or kidneys in all studied groups. In conclusion, the present study demonstrates the hepato-protective and reno-protective effects of oleuropein and hydroxytyrosol olive leaves extracts from BPA and its derivates toxicity.

  5. Comparative protective effects of royal jelly and cod liver oil against neurotoxic impact of tartrazine on male rat pups brain.

    Science.gov (United States)

    Mohamed, Amany Abdel-Rahman; Galal, Azza A A; Elewa, Yaser H A

    2015-09-01

    This study is aimed to evaluate the possible neurotoxic effect of tartrazine (T), an extensively used synthetic azo dye, as well as to determine the potential modulatory role of cod liver oil (CLO) or royal jelly (RJ) against such effects. For this purpose, thirty-six male rat pups were allocated into six groups. The 1st group received distilled water (control group), the 2nd group was given 300 mg RJ/kg bw (RJ group), the 3rd group was given 0.4 ml CLO/kg bw (CLO group), the 4th was given 500 mg T/kg bw (T group). The 5th group was given T concurrently with RJ (TRJ group) and the 6th group was given T concurrently with CLO (TCLO group), at the same doses as the former groups. All treatments were given orally for 30 consecutive days. The concentrations of different brain neurotransmitters, gamma amino butyric acid (GABA), dopamine (DA) and serotonin (5HT) as well as the antioxidant and oxidative stress biomarkers were measured in the brain homogenates. An immunohistochemical staining of the cerebral cortex was applied with the anti-ssDNA antibody (an apoptotic cell marker) to reveal the changes in brain structure. The T group revealed a significant decrease in the concentration of the brain neurotransmitters, a sharp shortage in the level of antioxidant biomarkers (super oxide dismutase, catalase and the reduced glutathione), a marked increase in malondialdehyde levels, and numerous apoptotic cells in the brain cortex compared with the other groups. Interestingly, all the previously mentioned parameters were almost retrieved in both the TRJ and TCLO groups compared to the T group. These results conclusively demonstrate that RJ and CLO administration provides sufficient protection against the ruinous effects of T on rat pups brain tissue function and structure.

  6. Lipid Peroxidation and Ultrastructural Modifications in Brain after Perinatal Exposure to Lead and/or Cadmium in Rat Pups

    Institute of Scientific and Technical Information of China (English)

    YU-MEI ZHANG; XUE-ZHONG LIU; HAO LU; LI MEI; ZONG-PING LIU

    2009-01-01

    Objective To assess lipid peroxidation and ultrastructural modifications in rat brains following perinatal exposure to lead (Pb) and/or cadmium (Cd). Methods Female rats were divided into four groups: control group, Pb (300 mg/L) group, Cd group (10 mg/L) and Pb+Cd (300 mg/L, 10 mg/L) group. The compounds were delivered in the drinking water throughout pregnancy and lactation. Results The levels of compounds in blood and brain of the Pb+Cd group were similar to those of other groups, but the effects of Pb+Cd on pups' body and brain weights were higher than on other compounds. Electron microscopy revealed that Pb and Cd had effects on mitochondrial swelling, disruption and cristae loss, Nissl body dissolution, degenerated organelles and vacuoles, cytomembrane disappearance, and nuclear ehromoplasm concentration. The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), acetylcholinesterase (ACHE) was decreased, whereas the activity of maleic dialdehyde (MDA) was increased. Conclusion Perinatal exposure to low doses of Pb and Cd can produce alterations in lipid peroxidation and ultrastructural modifications in rat brains, and exposure to both metals can result in greater damages.

  7. Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups

    Energy Technology Data Exchange (ETDEWEB)

    Valenzuela, A.; Nieto, S.; Sanhueza, J.; Morgado, N.; Rojas, I.; Zanartu, P.

    2010-07-01

    Docosahexaenoic acid (Dha) is supplied to the foetus and newborn through the mother from their own reserves and their diet. No consensus about the best form to supplement DHA has been established. We propose that DHA containing lysophosphatidylcholine (DHA-LPC), obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine) supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily.), before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT) activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mothers plasma and increases the pups DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period. (Author) 66 refs.

  8. The contribution of cell surface FcRn in monoclonal antibody serum uptake from the intestine in suckling rat pups

    Directory of Open Access Journals (Sweden)

    Philip R Cooper

    2014-10-01

    Full Text Available The neonatal Fc Receptor (FcRn in intestinal epithelium is the primary mechanism for transfer of maternal immunoglobulin G (IgG from suckled milk to serum; but the factors contributing to the rapid uptake of IgG are poorly understood. These studies help to determine the contribution of cell-surface FcRn in IgG uptake in 2-week old rat pups by varying local pH and binding conditions. Variants of a human wild-type IgG monoclonal antibody (mAb WT were assessed for binding affinity (KD to rat (rFcRn at pH6.0 and subsequent off-rate at pH7.4 (1/s by Surface Plasmon Resonance. Selected mAbs were administered intra-intestinally in isofluorane-anesthetized 2-week rat pups. Full-length mAb in serum was quantified by immunoassay, (rFcRn mRNA expression by RT-PCR, and mAb epithelial localization was visualized by immunohistochemistry. After duodenal administration, serum levels of mAb variants correlated with their rFcRn off-rate at pH7.4, but not their affinity at pH6.0. The greatest serum levels of IgG were measured when mAb was administered in the duodenum where rFcRn mRNA expression is greatest, and was increased further by duodenal administration in pH6.0 buffer. More intense human IgG immunostaining was detected in epithelium than the same variant administered at higher pH. These data suggest an increased contribution for cell-surface receptor. We conclude that, in the neonate duodenum, receptor off-rates are as important as affinities for FcRn mediated uptake, and cell surface binding of IgG to rFcRn plays contributes to IgG uptake alongside pinocytosis; both of which responsible for increased IgG uptake.

  9. N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.

    Directory of Open Access Journals (Sweden)

    Fernanda S Rodrigues

    Full Text Available BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I is characterized by accumulation of glutaric acid (GA and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life, and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period. LPS (2 mg/kg; E.coli 055 B5 or vehicle (saline 0.9% was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could

  10. N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups

    Science.gov (United States)

    Rodrigues, Fernanda S.; Souza, Mauren A.; Magni, Danieli V.; Ferreira, Ana Paula O.; Mota, Bibiana C.; Cardoso, Andreia M.; Paim, Mariana; Xavier, Léder L.; Ferreira, Juliano; Schetinger, Maria Rosa C.; Da Costa, Jaderson C.; Royes, Luiz Fernando F.; Fighera, Michele R.

    2013-01-01

    Background and Aims Glutaric aciduria type I (GA-I) is characterized by accumulation of glutaric acid (GA) and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS) in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC) on theses markers. Methods Rat pups were injected with GA (5umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150mg/kg/day; intragastric gavage; for the same period). LPS (2mg/kg; E.coli 055 B5) or vehicle (saline 0.9%) was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. Results GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance) content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. Conclusions These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could represent a possible

  11. Concurrent maternal and pup postnatal tobacco smoke exposure in Wistar rats changes food preference and dopaminergic reward system parameters in the adult male offspring.

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    Pinheiro, C R; Moura, E G; Manhães, A C; Fraga, M C; Claudio-Neto, S; Abreu-Villaça, Y; Oliveira, E; Lisboa, P C

    2015-08-20

    Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. Nursing Wistar rats and their pups were divided into two groups: tobacco smoke-exposed (S: 4times/day, from the 3rd to the 21th day of lactation), and ambient air-exposed (C). On PN175, both offspring groups were subdivided for a food challenge: S and C that received standard chow (SC) or that chose between high-fat (HFD) and high-sucrose diets (HSDs). Food intake was recorded after 30min and 12h. Offspring were tested in the elevated plus maze and open field on PN178-179; they were euthanized for dopaminergic analysis on PN180. SSD (self-selected diet) animals presented a higher food intake compared to SC ones. S-SSD animals ate more than C-SSD ones at 30min and 12h. Both groups preferred the HFD. However, S-SSD animals consumed relatively more HFD than C-SSD at 30min. No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Hypothalamic-pituitary adrenal (HPAA) axis function in adult Fischer-344 rats exposed during development to neurotoxic chemicals perinatally.

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    Rosecrans, J A; Johnson, J H; Tilson, H A; Hong, J S

    1984-01-01

    The major objective of these experiments was to determine long-term effects on the hypothalamic-pituitary adrenal axis (HPAA) of adult rats exposed during development to chlordecone, an organochlorine insecticide. Chlordecone was administered to mothers prenatally plus the first 12 days of the neonatal period (6 ppm in the diet) or neonatally via a single subcutaneous injection to rats at 4 days of age (1 mg/pup in 20 micrograms of DMSO). DMSO (20 microliters/pup) and dexamethasone (100 micrograms/pup in 20 microliters saline) were also injected on day 4. HPAA function was evaluated at 70-80 days of age. Responsiveness of the HPAA to a repeated stressor was evaluated by exposing rats of each treatment group to a 7-day stress-induced analgesia (SIA) paradigm consisting of a daily 15 sec foot-shock (0.9 mA) exposure which was preceded by a 15 sec white noise conditioned stimulus. The behavioral response to daily stress was evaluated by measuring tail-flick latencies immediately before and/or after each stress exposure. The conditioned response to stress was evaluated 24 hours after the last of 7 daily foot-shock sessions in which rats of each treatment and experimental group were exposed to the shock chamber only. All rats were killed 15 minutes after the final session and tissue (serum and adrenals) were removed and frozen for later chemical analysis; serum and adrenal corticosterone (CS) and serum prolactin (Prl) levels were measured. Perinatal exposure to chlordecone did not significantly alter the behavioral and/or neuroendocrine responses to stress. Ambient hormone levels (both CS and Prl), however, were uniformly attenuated by chlordecone.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

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    Aline Rideau Batista Novais

    Full Text Available Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

  14. Combined exposure to endocrine disrupting pesticides impairs parturition and causes pup mortality in rats

    DEFF Research Database (Denmark)

    Hansen, Pernille Reimer; Christiansen, Sofie; Boberg, Julie

    to five pesticides, i.e. procymidone, mancozeb, tebuconazole, epoxiconazole and prochloraz. Common features for the three azole fungicides are that they increase gestational length possibly because of an increase in progesterone levels in dams. Groups of 8 time-mated Wistar rats (HanTac:WH) were gavaged...

  15. Maternal deprivation of rat pups reduces body weight and alters behavior in adulthood in a gender-specific manner

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    Đorđević Jelena

    2015-01-01

    Full Text Available The early postnatal environment is critical for its capacity to influence adult behavior, and is associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Here we describe the delayed effects of maternal deprivation (MD in male and female Wistar pups on their physical development and behavior in adulthood in tasks designed to explore depressive-like (forced swimming test, FST, and anxiety-like behaviors (elevated plus maze, EPM. We observed that MD led to reduced body weight in adulthood, anxiety-like traits in the EPM test and increased activity in the phases of the FST. Particularly, a consistent sexual dimorphism was observed in the responses to MD. A lower increase in body weight during maturation of MD rats was more pronounced in males than in females. MD anxiogenic effects were more pronounced in females, while in FST only MD males showed a marked increase in swimming activity followed by decreased immobility. [Projekat Ministarstva nauke Republike Srbije, br. III41029

  16. In vivo digestomics of milk proteins in human milk and infant formula using a suckling rat pup model.

    Science.gov (United States)

    Wada, Yasuaki; Phinney, Brett S; Weber, Darren; Lönnerdal, Bo

    2017-02-01

    Human milk is the optimal mode of infant feeding for the first several months of life, and infant formulas serve as an alternative when breast-feeding is not possible. Milk proteins have a balanced amino acid composition and some of them provide beneficial bioactivities in their intact forms. They also encrypt a variety of bioactive peptides, possibly contributing to infant health and growth. However, there is limited knowledge of how milk proteins are digested in the gastrointestinal tract and bioactive peptides are released in infants. A peptidomic analysis was conducted to identify peptides released from milk proteins in human milk and infant formula, using a suckling rat pup model. Among the major milk proteins targeted, α-lactalbumin and β-casein in human milk, and β-lactoglobulin and β-casein in infant formula were the main sources of peptides, and these peptides covered large parts of the parental proteins' sequences. Release of peptides was concentrated to specific regions, such as residues 70-92 of β-casein in human milk, residues 39-55 of β-lactoglobulin in infant formula, and residues 57-96 and 145-161 of β-CN in infant formula, where resistance to gastrointestinal digestion was suggested. In the context of bioactive peptides, release of fragments containing known bioactive peptides was confirmed, such as β-CN-derived opioid and antihypertensive peptides. It is therefore likely that these fragments are of biological significance in neonatal health and development.

  17. Acupuncture stimulation at HT7 alleviates depression-induced behavioral changes via regulation of the serotonin system in the prefrontal cortex of maternally-separated rat pups.

    Science.gov (United States)

    Park, Hyemee; Yoo, Doyoung; Kwon, Sunoh; Yoo, Tae-Won; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae

    2012-07-01

    A possible application of acupuncture in alleviating depression-like behavioral changes and regulating serotonin signaling in the prefrontal cortex (PFC) of maternally-separated rat pups was investigated in this study. On postnatal day 15, rat pups were maternally-separated and received acupuncture stimulation at acupoint HT7 or ST36 once a day for 7 days. On postnatal day 21, the tail suspension test was performed and the PFC was harvested. Tissue levels of serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were then measured by high-performance liquid chromatography and expression of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) were assessed by western blotting. Levels of 5-HT and 5-HIAA were not significantly changed, but the 5-HIAA/5-HT ratio was significantly increased by maternal separation. The immobility time of maternally-separated rat pups was increased, and increased 5-HTT expression and reduced BDNF level were observed in the PFC. But acupuncture stimulation at HT7 alleviated the behavioral change and regulated the changes of 5-HIAA/5-HT ratio, 5-HTT, and BDNF. In conclusion, acupuncture stimulation at HT7 can relieve maternal separation-induced changes, and we propose that regulation of the 5-HIAA/5-HT ratio and of 5-HTT expression by acupuncture stimulation are important acupuncture-induced benefits in this animal model of depression.

  18. Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

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    Angel A. Puig-Lagunes

    2016-11-01

    Full Text Available Background Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD (20–25% than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA as autism model. Methods Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ and lithium-pilocarpine (Li-Pilo. Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+ (28/42, seizure severity 5 and a low susceptibility (VPA− (14/42, seizure severity 2. The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min, a higher number of rats showed several GTCS (14/28 and developed status epilepticus (SE after PTZ injection (19/27 compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively. No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

  19. On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

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    El-Gezeery Amina R

    2011-08-01

    Full Text Available Abstract Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA, serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA, serotonin (5HT and dopamine (DA as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6, tumor necrosis factor-α (TNF-α as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE, phosphatidylserine (PS and phosphatidylcholine (PC. Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as

  20. Lupeol, a pentacyclic triterpenoid isolated from Vernonia cinerea attenuate selenite induced cataract formation in Sprague Dawley rat pups.

    Science.gov (United States)

    Asha, Radha; Gayathri Devi, V; Abraham, Annie

    2016-02-05

    This study investigated the inhibitory effects of active component isolated from flavonoid fraction of Vernonia cinerea (FVC), lupeol on selenite induced cataract formation. Previous reports suggest that phytochemicals or natural plant products retard the process of cataractogenesis by scavenging free oxygen radicals. Hence, the present study sought to assess the potential of lupeol on in vivo selenite induced cataract models. Lupeol, a pentacyclic triterpenoid, was isolated from the ethyl acetate fraction of methanolic extract of Vernonia cinerea, follows standard chromatographic techniques. Structural elucidation of the compound was carried out using (1)H NMR, (13)C NMR, Mass spectrometry together with other complementary techniques (UV and IR). From these, the isolated compound was identified as Lupeol (3'-hydroxylup-20(29)-ene). The antioxidant activity was comparatively studied using DPPH radical scavenging and FRAP assay. Lupeol exhibited higher DPPH radical scavenging activity as well as reducing power assay. In this study, cataract was induced by a single subcutaneous injection of sodium selenite (4 μg/g body weight) on rat pups. Lupeol was administered orally from 8th day upto 21st day at a concentration 25 μg/g body weight. Cataract was visualized on 16th day with the help of an ophthalmoscope and later on with the naked eye. On the 30th day, rats were euthanized by sodium pentothal injection, lenses were excised and the biochemical parameters such as activity of superoxide dismutase (SOD), catalase (CAT), Glutathione peroxidase (GPx), Glutathione reductase (GR), Glutathione-S-transferase (GST), Ca(2+) ATPase, glutathione content (GSH), reactive oxygen species (ROS), lipid peroxidation products (malondialdehyde) were estimated and found effective in the treatment of cataract by lupeol.

  1. Influence of cafeteria diet and fish oil in pregnancy and lactation on pups' body weight and fatty acid profiles in rats.

    Science.gov (United States)

    Sánchez-Blanco, Clara; Amusquivar, Encarnación; Bispo, Kenia; Herrera, Emilio

    2016-06-01

    The aim was to determine the effects of cafeteria diet (CD) and fish oil supplements given to pregnant and lactating rats on the birth weight and fatty acid profiles of their offspring. Female rats were given standard diet (STD) or CD for 22 days before pregnancy. After mating, some animals remained on STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD-FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. At birth, body weights of pups of the three CD groups were lower than STD, maintained until 21 days in the CD-FO group only. At the end of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG), non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long-chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of Δ(5) and Δ(6) desaturase activities decreased. The 21-day-old pups of the CD group had increased plasma TAG, not present in the CD-FO group, which had increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups, plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO groups. The effect of CD and CD-FO decreasing pups body weight could be related to decreased concentrations of ARA, caused by the inhibition of the Δ(5) and Δ(6) desaturases in the pathway of n-6 LCPUFA biosynthesis.

  2. The Effect of Low Omega-3/Omega-6 Ratio on Auditory Nerve Conduction in Rat Pups.

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    Saeid Farahani

    2015-06-01

    Full Text Available The biological effects of omega-3 and omega-6 fatty acids are determined by their mutual interactions. This interaction extremely affects various functions. Lower consumption of omega-3 during gestation leads to various disorders, even in hearing. We aimed to assess the effect of low omega-3/omega-6 ratios on auditory nerve conduction. In this experimental study, the auditory brainstem response test was performed on 24-day-old rat (n=14. The rats were divided into case (low omega-3/omega-6 ratio during gestation and lactation and control groups. Variables such as P1, P3, and P4 absolute latency period, interpeaks (P3-P4, P1-P3, and P1-P4, and P4/P1 amplitude ratio were measured. We found an increased P4 omega-3/omega-6 ratio in the group with a low omega-3/omega-6 ratio (P0.05.  Also, no significant difference was observed between the groups with respect to the P1-P3 interpeak latency (IPL periods (P>0.05; while the P1-P4 and P3-P4 IPLs were significantly increased in the group with a low omega-3/omega-6 ratio (P<0.05. The P4/P1 amplitude ratio significantly decreased in the group with a low omega-3/omega-6 ratio (P<0.05. Results confirmed the negative effects of low omega-3/omega-6 ratio on the auditory system and hearing.

  3. Maternal Voluntary Exercise during Pregnancy Enhances the Spatial Learning Acquisition but not the Retention of Memory in Rat Pups via a TrkB-mediated Mechanism: The Role of Hippocampal BDNF Expression

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    Maziar M Akhavan

    2013-09-01

    Full Text Available   Objective(s: The effect of maternal voluntary exercise on hippocampal BDNF level in rat offspring was studied. In addition, the possible role of hippocampal BDNF receptors in maternal exercise induced enhancement of learning in the rat pups was investigated.   Materials and Methods: Pregnant rats have been randomly assigned to sedentary control or voluntary exercise groups. Each of the exercising pregnant rats was given access to a cage that was equipped with a running wheel until the end of their pregnancy. On post natal day (PND 36, two groups consisted of 7 male rat pups in each group from sedentary or exercised mothers were sacrificed and the hippocampus was dissected for BDNF proteins level determination. Also, bilateral injection of K252a to the hippocampus was used to block the hippocampal BDNF action on PND59 in the rat pups. Results: Voluntary exercise during pregnancy significantly increased the level of BDNF protein in the hippocampus of the rat pups on PND36 compared to the control group (P=0.048. Inhibiting BDNF action abolished the exercise-induced improvement of learning acquisition in offspring in training trials (P=0.0001. No difference was observed in the platform location latency and the time spent in the target in the probe test between two groups. Conclusion : This study demonstrates that voluntary exercise during pregnancy via a TrkB-mediated mechanism enhances the spatial learning acquisition, however, not the retention of memory in the rat pups.

  4. Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor.

    Science.gov (United States)

    You, Li; Sar, Madhabananda; Bartolucci, Erika J; McIntyre, Barry S; Sriperumbudur, Rajagopal

    2002-04-01

    The estrogenic isoflavone genistein is a common dietary component that has been shown to affect reproductive development in experimental animals at high doses. The objective of the present study was to examine interactions of genistein and the hormonally active pesticide methoxychlor on mammary gland development in juvenile rats. Timed-pregnant Sprague-Dawley rats were fed a soy- and alfalfa-free diet containing different combinations of genistein (300 and 800 ppm) and methoxychlor (800 ppm). Rats were fed these diets starting on gestation day (GD)1 and continuing through pregnancy and lactation until postnatal day (PND) 22, when the pups were killed. Inguinal mammary glands from both female and male pups were processed as whole-mount preparations for morphometric analysis. The total glandular area and the numbers of branch points, lateral buds, and terminal end buds in the male rats were found to be significantly greater in the groups exposed to methoxychlor than those exposed to genistein only. These effects were not observed in the female rats. In the male rats, methoxychlor had the most prominent effect on elongating the glandular ducts, while genistein enhanced the ductile branching. The 2 compounds in combination promoted the development of alveolar-lobular structure, an effect not observed with either compound alone. Immunostaining for proliferating cell nuclear antigen revealed a high percentage of immunopositive cells in the mammary epithelia of the males exposed to methoxychlor and genistein (800 ppm) compared to the controls. While no significant changes in serum levels of mammotrophic hormones were detected, increased immunostaining for insulin-like growth factor-1 receptor, estrogen receptor alpha, and progesterone receptor in the genistein + methoxychlor group suggested that local factors involved in regulating mammary growth may have played a role in propagating the endocrine effects of these two compounds. These results indicated that the mammary

  5. Comparison of stress-induced changes in adults and pups: is aldosterone the main adrenocortical stress hormone during the perinatal period in rats?

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    János Varga

    Full Text Available Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR and mineralocorticoid receptors (MR and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2, an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.

  6. Rapid acquisition of operant conditioning in 5-day-old rat pups: a new technique articulating suckling-related motor activity and milk reinforcement.

    Science.gov (United States)

    Arias, Carlos; Spear, Norman E; Molina, Juan Carlos; Molina, Agustin; Molina, Juan Carlos

    2007-09-01

    Newborn rats are capable of obtaining milk by attaching to a surrogate nipple. During this procedure pups show a gradual increase in head and forelimb movements oriented towards the artificial device that are similar to those observed during nipple attachment. In the present study the probability of execution of these behaviors was analyzed as a function of their contingency with intraoral milk infusion using brief training procedures (15 min). Five-day-old pups were positioned in a smooth surface having access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump which served to deliver intraoral milk reinforcement (Paired group). Yoked controls received the reinforcer when Paired neonates touched the sensor. Paired pups trained under a continuous reinforcement schedule emitted significantly more responses than Yoked controls following two (Experiment 1) or one training session (Experiment 2). These differences were also observed during an extinction session conducted immediately after training. The level of maternal deprivation before training (3 or 6 hr) or the volume of milk delivered (1.0 or 1.5 microl per pulse) did not affect acquisition or extinction performances. In addition, it was observed that the rate of responding of Paired pups during the early phase of the extinction session significantly predicted subsequent levels of acceptance of the reinforcer. These results indicate that the frequency of suckling-related behaviors can be rapidly modified by means of associative operant processes. The operant procedure here described represents an alternative tool for the ontogenetic analysis of self-administration or behavior processes of seeking.

  7. Supplementation of DHA-rich microalgal oil or fish oil during the suckling period in mildly n-3 fatty acid-deficient rat pups.

    Science.gov (United States)

    Kimura, Fumiko; Ito, Shiho; Endo, Yasushi; Doisaki, Nobushige; Koriyama, Tsuyoshi; Miyazawa, Teruo; Fujimoto, Kenshiro

    2011-12-01

    Long-chain polyunsaturated fatty acids (LC-PUFA), particularly arachidonic acid (ARA) and docosahexaenoic acid (DHA), are considered critical for the development of infants and are commonly supplemented in infant formulae. In this study, two common sources of n-3 LC-PUFA, fish oil (FO) and DHA-rich microalgal oil (DMO), were fed to rat pups of mildly n-3 PUFA-deficient dams to compare changes in LC-PUFA of tissue phospholipids. The milk from dams fed a n-3 PUFA-deficient diet contained less n-3 LC-PUFA than that of dams fed a control diet (AIN-93G). The pups' were given orally 1 mg/g weight of either FO or DMO for 17 days between the ages of 5 and 21 days, the pups were weaned, and sacrificed 1 week later for analysis of fatty acid compositions of brain, heart, kidney, spleen, and thymus phospholipids. Although both FO and DMO brought about a recovery in the tissue DHA levels compared to those of the control group (pups from AIN-93G-fed dams), DMO was more effective at restoring tissue LC-PUFA status because it was richer in DHA than FO. FO had a slightly lower PUFA level than that required to bring the LC-PUFA status completely to normal levels in this experiment, and EPA did not accumulate in tissues under the conditions tested here. These results demonstrate the effectiveness of ingesting either FO or DMO in the pre-weaning period for improving mild n-3 PUFA deficiency.

  8. Involvement of the strychnine-sensitive glycine receptor in the anxiolytic effects of GlyT1 inhibitors on maternal separation-induced ultrasonic vocalization in rat pups.

    Science.gov (United States)

    Komatsu, Hiroko; Furuya, Yoshiaki; Sawada, Kohei; Asada, Takashi

    2015-01-05

    Several studies have shown that glycine transporter 1 (GlyT1) inhibitors have anxiolytic actions. There are two types of glycine receptor: the strychnine-sensitive glycine receptor (GlyA) and the strychnine-insensitive glycine receptor (GlyB); however, which receptor is the main contributor to the anxiolytic actions of GlyT1 inhibitors is yet to be determined. Here, we clarified which glycine receptor is the main contributor to the anxiolytic effects of GlyT1 inhibitors by using maternal separation-induced ultrasonic vocalization (USV) by rat pups as an index of anxiety. We confirmed that administration of the benzodiazepine diazepam or the selective serotonin reuptake inhibitor escitaloplam, which are both clinically proven anxiolytics, or the GlyT1 inhibitor SSR504734 (2-chloro-N-[(S)-phenyl[(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide), decreases USV in rat pups. In addition, we showed that another GlyT1 inhibitor, ALX5407 ((R)-N-[3-(4'-fluorophenyl)-3(4'-phenylphenoxy)propyl]sarcosine) also decreases USV in rat pups. SSR504734- or ALX5407-induced decreases in USV were dose-dependently reversed by administration of the GlyA antagonist strychnine, whereas the diazepam- or escitalopram-induced decreases in USV were not. Furthermore, GlyT1-induced decreases in USV were not reversed by administration of the GlyB antagonist L-687,414. Together, these results suggest that GlyA activation is the main contributor to the anxiolytic actions of GlyT1 inhibitors and that the anxiolytic actions of diazepam and escitalopram cannot be attributed to GlyA activation. Our findings provide new insights into the importance of the activation of GlyA in the anxiolytic effects of GlyT1 inhibitors. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Effects of Fish Oil Supplementation during the Suckling Period on Auditory Neural Conduction in n-3 Fatty Acid-Deficient Rat Pups

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    vida rahimi

    2014-07-01

    Full Text Available Abstract Introduction: Omega 3 fatty acid especially in the form of fish oil, has structural and biological role in the body's various systems especially nervous system. Numerous studies have tried to research about it. Auditory is one of the affected systems. Omega 3 deficiency can have devastating effects on the nervous system and auditory. This study aimed to evaluate neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil consumption during the suckling period Materials and Methods: In this interventional and experimental study, one sources of omega3 fatty acid (fish oil were fed to rat pups of n-3 PUFA-deficient dams to compare changes in their auditory neural conduction with that of control and n-3 PUFA-deficient groups, using Auditory Brainstem Response (ABR. The parameters of interest were P1, P3, P4 absolute latency, P1-P3, P1-P4 and P3-P4 IPL , P4/P1 amplitude ratio . The rat pups were given oral fish oil, 5 Ml /g weight for 17 days, between the age of 5 and 21 days. Results There were no significant group differences in P1 and P3 absolute latency (p > 0.05. but the result in P4 was significant(P ≤ 0.05 . The n-3 PUFA deficient +vehicle had the most prolonged (the worst P1-P4 IPL and P3-P4 IPL compared with control and n-3 PUFA deficient + FO groups. There was no significant difference in P1-P4 IPL and P3-P4 IPL between n-3 PUFA deficient + FO and control groups (p > 0.05.There was a significant effect of diet on P1-P4 IPL and P3-P4 IPL between groups (P ≤ 0.05. Conclusion: The results of present study showed the effect of omega3 deficiency on auditory neural structure during pregnancy and lactation period. Additionally, we observed the reduced devastating effects on neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil during the suckling period

  10. Zinc absorption from low phytic acid genotypes of maize (Zea mays L.), Barley (Hordeum vulgare L.), and Rice (Oryza sativa L.) assessed in a suckling rat pup model.

    Science.gov (United States)

    Lönnerdal, Bo; Mendoza, Concepcion; Brown, Kenneth H; Rutger, J Neil; Raboy, Victor

    2011-05-11

    Dietary phytic acid is a major causative factor for low Zn bioavailability in many cereal- and legume-based diets. The bioavailability of Zn in seed of low phytic acid (lpa) variants of maize ( Zea mays L.), rice ( Oryza sativa L.), and barley ( Hordeum vulgare L.) was evaluated using a suckling rat pup model. Suckling rat pups (14 days old, n = 6-8/treatment) were fasted for 6 h and intubated with (65)Zn-radiolabeled suspensions prepared using seed produced by either wild-type (normal phytic acid) or lpa genotypes of each cereal. Test solutions were radiolabeled overnight (all genotypes) or immediately prior to intubation (barley genotypes). Pups were killed 6 h postintubation and tissues removed and counted in a gamma counter. Zn absorption was low from wild-type genotypes of maize (21, 33%) and rice (26%), and phytic acid reduction resulted in significantly higher Zn absorption, 47-52 and 35-52%, respectively. Zn absorption from wild-type barley incubated overnight was high (86-91%), and phytate reduction did not improve Zn absorption (84-90%), which is likely due to endogenous phytase activity. When the wild-type barley solutions were prepared immediately before intubation, Zn absorption was significantly lower (63, 78%) than from the lpa cultivars (92, 96%). Variation in seed or flour phenolic acid levels did not affect Zn absorption. Differences in seed Zn levels did not substantially affect Zn absorption. Thus, when phytic acid is abundant in a diet, it has a larger effect on Zn absorption than the level of Zn. Therefore, reducing the phytic acid content of staple cereal grains may contribute to enhancing Zn nutrition of populations consuming these staple foods.

  11. Peripheral Neuropathy in Rats Exposed to Dichloroacetate

    Science.gov (United States)

    Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W.

    2009-01-01

    The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144

  12. Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.S. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Swart, R.L. de [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands); Timmerman, H.H.; Loveren, H. van [National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Osterhaus, A.D.M.E. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands)

    1995-12-31

    Complex mixtures of lipophilic contaminants have been shown to affect certain top predators in the aquatic food chain, including seals. A recent demonstration that harbor seals (Phoca vitulina) fed Baltic Sea herring displayed impaired natural killer cell activity and T-lymphocyte function represented the first demonstration of immunotoxicity induced by ambient levels of contaminants in the environment. While these animals had a lower ability to respond to immunizations with inactivated vaccines, specific antibody responses, and in vitro antigen-specific lymphoproliferative responses, obvious constraints limited the ability to extend these results with host resistance tests or an evaluation of thymus and other lymphoid organs. The authors therefore set up a parallel study by exposing pregnant laboratory rats to the same Baltic herring contaminant mixture as received the seals. They then examined immune function parameters and host resistance to virus infection. As in the seals, rat pups of the Baltic group had impaired T-lymphocyte function. In addition, thymus cells and/or their precursors appeared to be targeted, as their numbers and function were reduced in the rats. Following challenge with rat cytomegalovirus in a host resistance study, rat pups in the Baltic group had impaired natural killer cell responses to the virus infection, and lower specific CD8 + (cytotoxic T-lymphocyte) responses following in vitro stimulation. By extrapolation, these results suggest that the impaired immune responses observed in the Baltic group of seals may lead to a less effective defense against virus infections in marine mammals inhabiting polluted coastal waters. Toxicological profiles and results of both the captive seal and laboratory rat experiments tend to implicate the 2,3,7,8-TCDD-like PCB, dioxin and furan congeners in the immunosuppression, and point to a major role for the PCBs.

  13. Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups.

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    Rojas, I.

    2010-03-01

    Full Text Available Docosahexaenoic acid (DHA is supplied to the foetus and newborn through the mother from their own reserves and their diet. No consensus about the best form to supplement DHA has been established. We propose that DHAcontaining lysophosphatidylcholine (DHA-LPC, obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily., before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mother’s plasma and increases the pups’ DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period.El ácido docosahexaenoico (DHA que requiere el feto y el recién nacido lo aporta la madre desde sus reservas y la dieta, por lo cual se sugiere suplementar a la madre con DHA. No hay consenso sobre la mejor forma de suplementación. Proponemos que un lisofosfolípido que contiene DHA y colina (DHA-LPC obtenido de huevos con alto contenido de DHA es

  14. Increased gluconeogenesis in rats exposed to hyper-G stress

    Science.gov (United States)

    Daligcon, B. C.; Oyama, J.; Hannak, K.

    1985-01-01

    The effect of glucogenesis on the plasma glucose and liver glycogen of rats exposed to hyper-G stress is investigated. Twelve male Sprague-Dawley rats are injected with C-14 lactate, alanine, of glycerol, and six of the rats are exposed to 3.1 G for 0.25, 0.50, and 1.0 hr. The plasma glucose and liver glycogen of the centrifuged and noncentrifuged rats are analyzed. A significant increase in the C-14 incorporation of the substrate into the plasma glucose and liver glycogen is observed in the centrifuged rats. The injection of 5-methoxyindole-2-carboxylic acid, a gluconeogenesis inhibitor, results in a blocked increase in plasma glucose and liver glycogen. The role of epinephrine on the hyperglycemic and liver glycogen responses of centrifuged rats is studied. It is concluded that the initial increase in plasma glucose and liver glycogen in rats exposed to hyper-G stress is the result of an increased rate of gluconeogenesis.

  15. Insulin Expression in Rats Exposed to Cadmium

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives To investigate the effects of cadmium exposure on insulin expression in rats. Methods Eighteen adult SD assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG (N-acyetyl-β-glucosaminidase) were determined. The gene expressions of metallothionein (MT) and insulin were also measured,and the oral glucose tolerance tests (OGTT) were carried out. Results The contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas.not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression the change of the expression of insulin, MT-Ⅰ and MT-Ⅱ genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.

  16. 电磁辐射对子代大鼠学习记忆功能的影响%Effects of electromagnetic radiation exposure on learning and memory function of rat pups

    Institute of Scientific and Technical Information of China (English)

    张丽; 王晋; 郭国祯

    2008-01-01

    Objective To determine whether exposure to electromagnetic radiation results in behavioral effects of rat pups.Methods Wistar rats,either male or female,were divided randomly into four groups respectively:control(CTR),100 seconds(S1),1000 seconds(S10)and 3000 seconds(S30),then each of them were exposed to electromagnetic radiation of 100 kV/m field amplitude of corresponding time.For the day of exposure till 2 months later.they were mated with the rats in the same group and their offspring were divided into four groups(F-GTB,F-S1,F-S10,F-S30)correspondingly.Behavioral changes occur in 2-month old and 6-month old rat pups were found between radiation groups and control,and in Y-maze test,beth male and female pups in F-S10 significantly learned fewer times than their control(total study times:male 14.6±3.9 vs 21.1±7.8,female13.4±3.0 vs 25.8±8.8;false times:male 3.5±2.4 vs 7.8±5.4,female 3.4±2.6 vs 11.0±7.2).In open field test,both maze,male pups in F-S1 and F-S30 learned more times than control in total study time(24.2±8.9 vs 14.1±5.2.30.7±12.4 vs 14.1±5.2).In step throush test and open field test,no significant differences were found between radiation groups and control.Conclusion There was significant genetic effect exposed to electromagnetic radiation of 100 kV/m,mainly manifested in rat pups in growth period but without long-term effect.%目的 研究电磁辐射对子代大鼠学习记忆能力的影响.方法 健康Wistar大鼠分为雌雄2组,每组又随机分为4组:对照组(CRT)、100s组(SI)、1000 s组(S10)和3000 s组(S30)组,分别接受0s、100s、1000 s和3000 s电磁辐射(场强100kV/m).辐照后2月将辐照时间相同的雌性和雄性动物合笼生育子代,子代雌雄2组根据其亲代的分组方式相应分为F-CTR、F-S1、F-S10、F-S30(F指子代),各4组,每组20只.通过行为学实验检测2月龄和6月龄子代大鼠的学习记忆能力.结果 (1)2月龄子代大鼠:穿梭实验中各辐照组与对照组比均差异

  17. Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats.

    Directory of Open Access Journals (Sweden)

    Emmanuel Somm

    Full Text Available Poor fetal growth, also known as intrauterine growth restriction (IUGR, is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN. Physiological (glucose and insulin tolerance, morphometric (automated tissue image analysis and transcriptomic (quantitative PCR approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

  18. Effect of nebivolol treatment during pregnancy on the intrauterine fetal growth, mortality and pup postnatal development in the l-NAME-induced hypertensive rats.

    Science.gov (United States)

    Altoama, Kassem; Mallem, Mohamed Yassine; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

    2016-11-15

    The present study was carried out to evaluate the effect of nebivolol vs. bisoprolol treatment on the intrauterine fetal growth, mortality and postnatal development in N(ω)-Nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Hypertension was induced in normotensive pregnant Wistar rats by daily administration of l-NAME (100mg/kg/day, in the drinking water) for the period of pregnancy. After 9 days of l-NAME treatment, rats with systolic and diastolic blood pressure (SBP and DBP) more than 140/90mmHg were considered hypertensive. Then, some of them were treated from day 11 to day 18 of pregnancy with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) via oral gavage. SBP, DBP and heart rate (HR) were re-evaluated by tail cuff method on day 19 of pregnancy and morphometrical or histological studies were performed on day 20. In addition, the mortality and postnatal development of newborn pups were assessed in all groups. The l-NAME administration during pregnancy induced an increase in SBP and DBP while HR did not change. Nebivolol or bisoprolol treatment completely prevented the elevation of SBP and DBP induced by l-NAME with a reduction in HR in pregnant and non-pregnant rats. The intra-uterine fetal growth and the postnatal development of newborn rats in nebivolol-treated hypertensive group were significantly lower vs. control and higher vs. bisoprolol-treated group with a higher mortality in the both types of treatments vs. control rats. The nebivolol and bisoprolol administration produce adverse effects on fetal growth and postnatal development, that limits their therapeutic use in females during pregnancy.

  19. Two-Year Chronic Bioassay study of Rats Exposed to a 1.6 GHz Radiofrequency Signal.

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Larry E.; Sheen, David M.; Wilson, Bary W.; Grumbein, Sondra L.; Creim, Jeffrey A.; Sasser, Lyle B.

    2004-08-06

    The purpose of this study was to determine whether long-term exposure to a 1.6 GHz radiofrequency (RF) field would affect the incidence of cancer in Fischer 344 rats. Thirty-six timed-pregnant rats were randomly assigned to each of three treatment groups: two groups exposed to a far-field RF Iridium signal and a third group that was sham exposed. Exposures were chosen such that the brain SAR in the fetuses was 0.16 W/kg. Whole-body far-field exposures were initiated at 19 days of gestation and continued at 2 h/day, 7 days/week for dams and pups after parturition until weaning ({approx}23 days old). The offspring (700) of these dams were selected, 90 males and 90 females for each near-field treatment group, with SAR levels in the brain calculated to be as follows: (1) 1.6 W/kg, (2) 0.16 W/kg and (3) near-field sham controls with an additional 80 males and 80 females as shelf controls. Confining, head-first, near-field exposures of 2 h/day, 5 days/week were initiated when the offspring were 36 + 1 days old and continued until the rats were 2 years old. No statistically significant differences were observed among treatment groups for number of live pups/litter, survival index and weaning weights, nor were there differences in clinical signs or neoplastic lesions among the treatment groups. The percentages of animals surviving at the end of the near-field exposure were not different among the male groups. In females a significant decrease in survival time was observed for the case control group.

  20. Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons.

    Science.gov (United States)

    Magnusson, Jennifer; Cummings, Kevin J

    2015-11-15

    The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long-term facilitation of breathing (vLTF) and BP following AIH. We exposed 2-wk-old, 5,7-dihydroxytryptamine-treated and controls to AIH (10% O2; n = 13 control, 14 treated), acute intermittent hypercapnia (5% CO2; n = 12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O2, 5% CO2; n = 15 and 17). We gave five 5-min challenges of AIH and acute intermittent hypercapnia, and twenty ∼20-s challenges of AIHH to mimic sleep apnea. Systolic BP (sBP), diastolic BP, mean arterial pressure, heart rate (HR), ventilation (V̇e), and metabolic rate (V̇o2) were continuously monitored. 5,7-Dihydroxytryptamine induced an ∼35% loss of 5-HT neurons from the medullary raphe. Compared with controls, pups deficient in 5-HT neurons had reduced resting sBP (∼6 mmHg), mean arterial pressure (∼5 mmHg), and HR (56 beats/min), and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased V̇e and V̇e/V̇o2, and decreased arterial Pco2. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 h following AIHH. Our data suggest that a relatively small loss of 5-HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardiorespiratory defects related to partial 5-HT system dysfunction.

  1. Neurobehavioral toxicity in progeny of rat mothers exposed to methylmercury during gestation

    Directory of Open Access Journals (Sweden)

    Dinesh N. Gandhi

    2014-03-01

    Full Text Available INTRODUCTION: Methylmercury (MeHg is recognized as one of the most hazardous environmental pollutants. This may be a concern to long-term consumption of contaminated fish and seafood for health risk to pregnant women and their children. AIM: An animal study was conducted to assess the effect of MeHg exposure on rodent offspring following in utero exposure. METHODS: Pregnant Wister rats were treated by gavage with MeHg at dose levels of 0.5, 1.0 and 2.0 mg/kg/day from gestation day (GD 5 till parturition, and then were allowed to deliver. RESULTS: Dams treated with 2.0 mg/kg/day MeHg group showed signs of toxicity such as gait alterations and hyperactivity resulting in the failure to deliver sustainable viable pups. MeHg had significant effects on body weight gain of dams during GD 5 till parturition. MeHg had no significant effects on the ages of physical developments such as pinna detachment, incisor eruptions or eye opening as well as alter cliff avoidance, surface righting, swimming ontogeny, startle reflex, pivoting, negative geotaxis, or forelimb and hindlimb grip strength in either sex. Exposure to 1.0 mg/kg/day MeHg treatment group prolonged gestation period, retard mid-air righting in male pups, shortened forelimb grip strength measured on rotating rod in either sex and enhanced open field behaviour in male pups. Data obtained from Functional Observation Battery (FOB also revealed impairment of neuromotor performance in male pups. The male pups appeared to be more susceptible than the female pups. CONCLUSION. Overall, the dose level of MeHg in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter neuromotor performance of the male pups.

  2. Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development.

    Science.gov (United States)

    Rao Barkur, Rajashekar; Bairy, Laxminarayana K

    2015-01-01

    Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learning and spatial learning in male rat pups exposed to lead through their mothers during specific periods of early brain development. Experimental male rats were divided into 5 groups: i) the normal control group (NC) (N = 12) consisted of rat offspring born to mothers who were given normal drinking water throughout gestation and lactation, ii) the pre-gestation lead exposed group (PG) (N = 12) consisted of rat offspring, mothers of these rats had been exposed to 0.2% lead acetate in the drinking water for 1 month before conception, iii) the gestation lead exposed group (G) (N = 12) contained rat offspring born to mothers who had been exposed to 0.2% lead acetate in the drinking water throughout gestation, iv) the lactation lead exposed group (L) (N = 12) had rat offspring, mothers of these rats exposed to 0.2% lead acetate in the drinking water throughout lactation and v) the gestation and lactation lead exposed group (GL) (N = 12) contained rat offspring, mothers of these rats were exposed to 0.2% lead acetate throughout gestation and lactation. The study found deficit in passive avoidance learning in the G, L and GL groups of rats. Impairment in spatial learning was found in the PG, G, L and GL groups of rats. Interestingly, the study found that gestation period only and lactation period only lead exposure was sufficient to cause deficit in learning and memory in rats. The extent of memory impairment in the L group of rats was comparable with the GL group of rats. So it can be said that postnatal period of brain development is more sensitive to neurotoxicity compared to prenatal exposure. This work is available in Open

  3. Locomotor activity and sensory-motor developmental alterations in rat offspring exposed to arsenic prenatally and via lactation.

    Science.gov (United States)

    Gumilar, Fernanda; Lencinas, Ileana; Bras, Cristina; Giannuzzi, Leda; Minetti, Alejandra

    2015-01-01

    Arsenic (As) is one of the most toxic naturally occurring contaminants in the environment. The major source of human exposure to inorganic As (iAs) is through contaminated drinking water. Although both genotoxicity and carcinogenicity derived from this metalloid have been thoroughly studied, the effects of iAs on the development and function of the central nervous system (CNS) have received less attention and only a few studies have focused on neurobehavioral effects. Thus, in order to characterize developmental and behavioral alterations induced by iAs exposure, pregnant Wistar rats were exposed to 0.05 and 0.10 mg/L iAs through drinking water during gestation and lactation. Sensory-motor reflexes in each pup were analyzed and the postnatal day when righting reflex, cliff aversion and negative geotaxis were recorded. Functional Observational Battery (FOB) and locomotor activity in an open field were assessed in 90-day-old offspring. Results show that rats exposed to low iAs concentrations through drinking water during early development evidence a delay in the development of sensory-motor reflexes. Both FOB procedure and open-field tests showed a decrease in locomotor activity in adult rats. This study reveals that exposure to the above-mentioned iAs concentrations produces dysfunction in the CNS mechanisms whose role is to regulate motor and sensory development and locomotor activity.

  4. Lateralized odor preference training in rat pups reveals an enhanced network response in anterior piriform cortex to olfactory input that parallels extended memory.

    Science.gov (United States)

    Fontaine, Christine J; Harley, Carolyn W; Yuan, Qi

    2013-09-18

    The present study examines synaptic plasticity in the anterior piriform cortex (aPC) using ex vivo slices from rat pups given lateralized odor preference training. In the early odor preference learning model, a brief 10 min training session yields 24 h memory, while four daily sessions yield 48 h memory. Odor preference memory can be lateralized through naris occlusion as the anterior commissure is not yet functional. AMPA receptor-mediated postsynaptic responses in the aPC to lateral olfactory tract input, shown to be enhanced at 24 h, are no longer enhanced 48 h after a single training session. Following four spaced lateralized trials, the AMPA receptor-mediated fEPSP is enhanced in the trained aPC at 48 h. Calcium imaging of aPC pyramidal cells within 48 h revealed decreased firing thresholds in the pyramidal cell network. Thus multiday odor preference training induced increased odor input responsiveness in previously weakly activated aPC cells. These results support the hypothesis that increased synaptic strength in olfactory input networks mediates odor preference memory. The increase in aPC network activation parallels behavioral memory.

  5. Antioxidant status in MgO nanoparticle-exposed rats.

    Science.gov (United States)

    Kiranmai, G; Reddy, A Rama Narsimha

    2013-11-01

    In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant (p MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures.

  6. Postnatal neurobehavioral development in rats exposed in utero to caffeine.

    Science.gov (United States)

    West, G L; Sobotka, T J; Brodie, R E; Beier, J M; O'Donnell, M W

    1986-01-01

    Potential behavioral and teratogenic effects of caffeine were studied in Charles River CD albino rats. Caffeine in distilled water was given by gavage to pregnant rats (dams) at doses of 5, 25, 50 or 75 mg/kg on Days 3-19 of gestation. Concurrent controls received distilled water gavage (10 ml/kg) on the same days. Dams were allowed to deliver normally. Physical and behavioral observations were made on dams during gestation and lactation and on F1 offspring through 9 weeks of age. Caffeine decreased body weights and food intake and increased water intake in gestating dams but these effects dissipated during lactation. Spontaneous locomotor activity (PAC) and open field (OF) were increased immediately after caffeine gavage but not before. Parturition was slightly delayed. With analyses of data based on individual pups the following effects were noted. Pre- and post-weaning offspring body weights were decreased in females at 50 and 75 mg/kg and in males at 75 mg/kg. Incisor eruption was delayed in females at 5, 50 and 75 mg/kg and in males at all doses. Auditory startle developed earlier in the 5 mg/kg dose group but was delayed at 75 mg/kg for males only. Eye opening was delayed in both sexes at 25, 50 and 75 mg/kg. In females, vaginal opening was delayed at 5, 25 and 75 mg/kg and 9-week ovary weights were increased at 75 mg/kg. In postweaning males, food intake was decreased and water intake was increased with increasing dose. In males, PAC was decreased at 75 mg/kg only on Day 12. At 7 weeks of age, step-down passive avoidance was decreased at 5 and 25 mg/kg but increased at 50 and 75 mg/kg, and at 8 weeks of age, shuttlebox active avoidance was decreased with increasing dose. Maternal and offspring behaviors were only weakly correlated. Correction for litter effect in developmental data yielded fewer significant results and only at 50 and 75 mg/kg. The issue of whether it is always appropriate to correct for "litter effect" is discussed.

  7. Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

    Directory of Open Access Journals (Sweden)

    C.D. Cisternas

    2010-09-01

    Full Text Available We studied the effects of adverse conditions such as constant light (LL on the circadian rhythm of malate (MDH, EC 1.1.1.37 and lactate (LDH, EC 1.1.1.27 dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28, anxiety-like behavior (elevated plus-maze test at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark, LL (light from day 10 to 21 of pregnancy, and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy. LL offspring did not show circadian rhythms of MDH (N = 62 and LDH (N = 63 activities (cosinor and ANOVA-LSD Fisher. They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test, an increase in mounting (94.4%, intromission (94.5% and ejaculation (56.6% latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12 compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher, anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

  8. Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups.

    Science.gov (United States)

    Gien, Jason; Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H

    2016-12-01

    Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ETA (BQ123/BQ610) and ETB (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1-ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. Copyright © 2016 the American Physiological Society.

  9. Effects of expression of surfactant protein A and B mRNAs in lung of rat pups from maternal passive smoking%孕期被动吸烟对新生大鼠肺SP-A和SP-B mRNAs表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    蔡栩栩; 杜悦; 高红; 李书琴; 李岩; 孟菲

    2004-01-01

    Objective:To study if prenatal exposure to sidestream cigarette smoke influences the expression of suffactant protein A(SP-A)and surfactant protein B(SP-B)mRNAs in the lung of rat pups.Methods:Sprague-Dawley rats on pregnant day 1,8 and 15 were exposed to sidestream cigarette smoke in a whole-body exposure chamber for 2 h each day.The pups were delivered by cesarean section on the 20thday of gestation.Reverse transcription polymerase chain reaction(RT-PCR)was used to evaluate relative amount of SP-A and SP-B mRNAs expression.Results:The relative amount of SP-A and SP-B mRNAs in the lung of rat pups did not show any significant difference between the control and smoke-exposed groups at any exposure point.Conclusions:The results indicate that prenatal exposure to sidestream smoke does not influence the expression of SP-A and SP-B mRNAs.%目的研究孕期被动吸烟对新生大鼠肺表面活性蛋白A、B(SP-A,SP-B)基因表达的影响,探讨产前被动吸烟对新生大鼠肺损伤的机制.方法分别将SD大鼠于妊娠第1、8和15天置于吸烟箱内每天2 h被动吸烟建立孕鼠被动吸烟动物模型,孕鼠每天置于吸烟箱内2 h不吸烟者为对照组,于妊娠第20天剖宫取胎鼠,采用反转录聚合酶链反应(RT-PCR)方法检测新生鼠肺组织SP-A、SP-B mRNAs的表达.结果不同孕期被动吸烟SD大鼠所产新生鼠肺组织SP-A、SP-B mRNAs的表达与对照比较和组间无明显差异(P>0.05).结论孕期被动吸烟对新生大鼠肺组织SP-A和SP-B mRNAs的表达无明显影响.

  10. A role for the anterior piriform cortex in early odor preference learning: evidence for multiple olfactory learning structures in the rat pup.

    Science.gov (United States)

    Morrison, Gillian L; Fontaine, Christine J; Harley, Carolyn W; Yuan, Qi

    2013-07-01

    cFos activation in the anterior piriform cortex (aPC) occurs in early odor preference learning in rat pups (Roth and Sullivan 2005). Here we provide evidence that the pairing of odor as a conditioned stimulus and β-adrenergic activation in the aPC as an unconditioned stimulus generates early odor preference learning. β-Adrenergic blockade in the aPC prevents normal preference learning. Enhancement of aPC cAMP response element-binding protein (CREB) phosphorylation in trained hemispheres is consistent with a role for this cascade in early odor preference learning in the aPC. In vitro experiments suggested theta-burst-mediated long-term potentiation (LTP) at the lateral olfactory tract (LOT) to aPC synapse depends on N-methyl-D-aspartate (NMDA) receptors and can be significantly enhanced by β-adrenoceptor activation, which causes increased glutamate release from LOT synapses during LTP induction. NMDA receptors in aPC are also shown to be critical for the acquisition, but not expression, of odor preference learning, as would be predicted if they mediate initial β-adrenoceptor-promoted aPC plasticity. Ex vivo experiments 3 and 24 h after odor preference training reveal an enhanced LOT-aPC field excitatory postsynaptic potential (EPSP). At 3 h both presynaptic and postsynaptic potentiations support EPSP enhancement while at 24 h only postsynaptic potentiation is seen. LOT-LTP in aPC is excluded by odor preference training. Taken together with earlier work on the role of the olfactory bulb in early odor preference learning, these outcomes suggest early odor preference learning is normally supported by and requires multiple plastic changes at least at two levels of olfactory circuitry.

  11. Lactational exposure to sulpiride: assessment of maternal care and reproductive and behavioral parameters of male rat pups.

    Science.gov (United States)

    Vieira, Milene Leivas; Dos Santos, Alice Hartmann; Silva, Luiza Sienna; Fernandes, Glaura Scantamburlo Alves; Kiss, Ana Carolina Inhasz; Moreira, Estefânia Gastaldello; Mesquita, Suzana de Fátima Paccola; Gerardin, Daniela Cristina Ceccatto

    2013-10-02

    Dopaminergic receptor antagonists may be used as galactagogues because they increase serum prolactin (PRL) by counteracting the inhibitory influence of dopamine on PRL secretion. The antipsychotic drug sulpiride (SUL) is documented to be effective as a galactagogue, but it is transferred through milk to the neonates. The aim of the present study was to evaluate if maternal exposure to SUL during lactation could disrupt maternal care and/or male offspring reproductive development. The dams were treated daily (gavage) with SUL 2.5mg/kg or 25mg/kg during lactation. Maternal behavior was analyzed on lactational days 5 and 10. In offspring, reproductive and behavioral parameters were analyzed at different time points. SUL treatment did not impair maternal care, but caused testicular damage in male offspring. At postnatal day 90, a reduction in testis weight, volume of seminiferous tubule and histopathological alterations such as an increased percentage of abnormal seminiferous tubules were observed. Data shows that maternal exposure to SUL during lactation may impact the reproductive development of male rats and the testes seem to be the main target organ at adulthood.

  12. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

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    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  13. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    Science.gov (United States)

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal.

  14. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Directory of Open Access Journals (Sweden)

    Belinda C. Gómez-Meda

    2016-01-01

    Full Text Available Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs and micronucleated polychromatic erythrocytes (MNPCEs in the samples from pups in the experimental groups (P<0.02 and increased MNPCE frequencies in the samples from the dams (P<0.05. These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects.

  15. Micronucleated Erythrocytes in Peripheral Blood from Neonate Rats Exposed by Breastfeeding to Cyclophosphamide, Colchicine, or Cytosine-Arabinoside

    Science.gov (United States)

    Bañales-Martínez, Luis R.; Lemus-Varela, María de Lourdes; Trujillo, Xóchitl; Sánchez-Parada, María G.; Armendáriz-Borunda, Juan; Zúñiga-González, Guillermo M.

    2016-01-01

    Genotoxic exposure to chemical substances is common, and nursing mothers could transmit harmful substances or their metabolites to their offspring through breast milk. We explored the possibility of determining genotoxic effects in the erythrocytes of breastfeeding rat pups whose mothers received a genotoxic compound while nursing. Ten groups of female rats and five pups per dam were studied. The control group received sterile water, and the experimental groups received one of three different doses of cyclophosphamide, colchicine, or cytosine-arabinoside. Blood smears were prepared from samples taken from each dam and pup every 24 h for six days. There were increased numbers of micronucleated erythrocytes (MNEs) and micronucleated polychromatic erythrocytes (MNPCEs) in the samples from pups in the experimental groups (P < 0.02) and increased MNPCE frequencies in the samples from the dams (P < 0.05). These results demonstrate the vertical transmission of the genotoxic effect of the compounds tested. In conclusion, assessing MNEs in breastfeeding neonate rats to assess DNA damage may be a useful approach for identifying genotoxic compounds and/or cytotoxic effects. This strategy could help in screening for therapeutic approaches that are genotoxic during the lactation stage and these assessments might also be helpful for developing preventive strategies to counteract harmful effects. PMID:28018917

  16. Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy

    Directory of Open Access Journals (Sweden)

    V.A. da-Silva

    1999-01-01

    Full Text Available The aim of the present study was to compare the toxic effects of fluoxetine (F (8 and 16 mg/kg and venlafaxine (V (40 and 80 mg/kg administered during the third week of pregnancy on early development of rats. Both antidepressants were administered by gavage on pregnancy days 15 to 20 to groups of 10 to 12 animals each. Duration of gestation, food and water consumption, number of live pups and birth weight were recorded. Litters were culled to six pups at birth (day 1 and followed for growth until weaning (day 25. On day 60, a male and a female from each litter were injected with the 5-HT1 agonist, 5-methoxy-N,N-dimethyltryptamine (6 mg/kg, ip and the serotonergic syndrome was graded. Fluoxetine but not venlafaxine reduced the duration of pregnancy when compared to the control (C group (F = 21.1 days and C = 21.6 days, mean, P<0.02; maximum = 22 days and minimum = 21 days in both groups. The highest doses of both fluoxetine, 16 mg/kg (F16, and venlafaxine, 80 mg/kg (V80, reduced the food intake of pregnant rats, resulting in different rates of body weight gain during treatment (from pregnancy day 15 to day 20: F16 = 29.0 g, V80 = 28.7 g vs C = 39.5 g (median. Birth weight was influenced by treatment and sex (P<0.05; two-way ANOVA. Both doses of fluoxetine or venlafaxine reduced the body weight of litters; however, the body weight of litters from treated dams was equal to the weight of control litters by the time of weaning. At weaning there was no significant difference in weight between sexes. There was no difference among groups in number of live pups at birth, stillbirths, mortality during the lactation period or in the manifestation of serotonergic syndrome in adult rats. The occurrence of low birth weight among pups born to dams which did not show reduced food ingestion or reduction of body weight gain during treatment with lower doses of fluoxetine or venlafaxine suggests that these drugs may have a deleterious effect on prenatal

  17. Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction.

    Science.gov (United States)

    Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

    2008-08-22

    Environmental stimuli such as caloric availability during the perinatal period exert a profound influence on the development of an organism. Studies in this domain have focused on the effects of under- and malnutrition while the effects of more mild levels of restriction have not been delineated. Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). The pup retrieval test and maternal observations were conducted during lactation to quantify maternal care. In the pup retrieval test, dams that were concurrently experiencing CR (i.e., from the lactation and lifelong groups) displayed shorter latencies to retrieve all pups than the control and preconception groups and the lactation group constructed better nests than all groups. Adult offspring were tested in three tests of anxiety: the elevated plus maze, open field, and emergence test. No differences were observed in the elevated plus maze; however, in the open field preconception animals made fewer entries and spent more time in the central zone than controls. In addition, preconception offspring exhibited longer latencies to full body emergence, spent less time fully emerged, and spent more time engaged in risk assessment behaviours than all other groups. Offspring from the preconception group were also on average 11% heavier than control rats throughout life and displayed 37% higher serum leptin concentrations than controls. A potential role for leptin in the anxiogenic effect of preconception CR is discussed.

  18. Neonatal handling prevents anxiety-like symptoms in rats exposed to chronic mild stress: behavioral and oxidative parameters.

    Science.gov (United States)

    Boufleur, Nardeli; Antoniazzi, Caren T D; Pase, Camila S; Benvegnú, Dalila M; Dias, Verônica T; Segat, Hecson J; Roversi, Katiane; Roversi, Karine; Nora, Magali Dalla; Koakoskia, Gessi; Rosa, João G; Barcellos, Leonardo J G; Bürger, M E

    2013-05-01

    This study investigated the influence of neonatal handling on behavioral and biochemical consequences of chronic mild stress (CMS) in adulthood. Male rat pups were submitted to daily tactile stimulation (TS) or maternal separation (MS), from postnatal day 1 (PND1) to postnatal day 21 (PND21), for 10 min/day. In adulthood, half the number of animals were exposed to CMS for 3 weeks and submitted to behavioral testing, including sucrose preference (SP), elevated plus maze (EPM), and defensive burying tasks (DBTs), followed by biochemical assessments. CMS reduced SP, increased anxiety in EPM and DBT, and increased adrenal weight. In addition, CMS decreased plasma vitamin C (VIT C) levels and increased protein carbonyl (PC) levels, catalase (CAT) activity in hippocampus and cortex, and superoxide dismutase (SOD) levels in cortex. In contrast, both forms of neonatal handling were able to prevent reduction in SP, anxiety behavior in DBT, and CMS-induced adrenal weight increase. Furthermore, they were also able to prevent plasma VIT C reduction, hippocampal PC levels increase, CAT activity increase in hippocampus and cortex, and SOD levels increase in cortex following CMS. Only TS was able to prevent CMS-induced anxiety symptoms in EPM and PC levels in cortex. Taken together, these findings show the protective role of neonatal handling, especially TS, which may enhance ability to cope with stressful situations in adulthood.

  19. Alaska Steller Sea Lion Pup Count Database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This database contains counts of Steller sea lion pups on rookeries in Alaska made between 1961 and 2015. Pup counts are conducted in late June-July. Pups are...

  20. Changes of cell factor in bronchoalveolar lavage fluid in rats exposed to silica

    Institute of Scientific and Technical Information of China (English)

    张玮

    2014-01-01

    Objective To investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid(BALF)in rats exposed to silica dust.Methods Experimental rats were randomly divided into control group and three experimental groups(doses of dust:15,30,and 60mg/ml),with 42 rats in each group.Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation,while each rat in the experimental groups was exposed to 1

  1. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Boberg, Julie; Vinggaard, Anne Marie

    2013-01-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T4) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout...... gestation and lactation. Total T4 serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T4 in dams, but no significant effects on T4 levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure...... through maternal milk, a second study using direct per oral pup exposure from postnatal day 3–16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T4 reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing...

  2. Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

    DEFF Research Database (Denmark)

    Olsen, P.; Meyer, Otto A.; Bille, N.

    1986-01-01

    Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex...... were formed from 40, 29, 30 and 44 litters, respectively. After weaning, the highest dose (500 mg BHT/kg/day) was lowered to 250 mg/kg/day for the F1 rats. The numbers of litters of ten or more pups at birth decreased with increasing BHT dose. At weaning, treated F1 rats had lower body weights than...... the controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found...

  3. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  4. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane.

    Science.gov (United States)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Hu, Shijie; Huang, Hanlin; Ichihara, Gaku

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn(2+))-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p<0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn(2+)-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity.

  5. Effect of phytate reduction of sorghum, through genetic modification, on iron and zinc availability as assessed by an in vitro dialysability bioaccessibility assay, Caco-2 cell uptake assay, and suckling rat pup absorption model.

    Science.gov (United States)

    Kruger, Johanita; Taylor, John R N; Du, Xiaogu; De Moura, Fabiana F; Lönnerdal, Bo; Oelofse, André

    2013-11-15

    Improved iron and zinc availability from sorghum, a commonly consumed staple, will benefit many malnourished communities in rural Africa burdened with high prevalence of iron and zinc deficiency. This research compared the effect of genetic phytate reduction in sorghum on iron and zinc bioaccessibility and uptake measured by in vitro dialysability and Caco-2 cell uptake assays to that of iron and zinc absorption measured by a suckling rat pup model. The phytate reduction (80-86%) in these sorghums significantly increased zinc availability. The Caco-2 cell method, but not the dialysability assay, proved useful in estimating zinc absorption. The measured increase in iron availability differed between the methods, possibly due to the effect of varying mineral (Ca, Fe, Zn, P) contents of the sorghums. This effect was most prominent in the iron uptake results. More research is needed to determine the effect of naturally occurring variations in mineral contents of sorghum on the iron uptake by Caco-2 cells.

  6. Analysis of emotionality and locomotion in radio-frequency electromagnetic radiation exposed rats.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Paval, Jaijesh; Kedage, Vivekananda; Bhat, M Shankaranarayana; Nayak, Satheesha; Bhat, P Gopalakrishna

    2013-07-01

    In the current study the modulatory role of mobile phone radio-frequency electromagnetic radiation (RF-EMR) on emotionality and locomotion was evaluated in adolescent rats. Male albino Wistar rats (6-8 weeks old) were randomly assigned into the following groups having 12 animals in each group. Group I (Control): they remained in the home cage throughout the experimental period. Group II (Sham exposed): they were exposed to mobile phone in switch-off mode for 28 days, and Group III (RF-EMR exposed): they were exposed to RF-EMR (900 MHz) from an active GSM (Global system for mobile communications) mobile phone with a peak power density of 146.60 μW/cm(2) for 28 days. On 29th day, the animals were tested for emotionality and locomotion. Elevated plus maze (EPM) test revealed that, percentage of entries into the open arm, percentage of time spent on the open arm and distance travelled on the open arm were significantly reduced in the RF-EMR exposed rats. Rearing frequency and grooming frequency were also decreased in the RF-EMR exposed rats. Defecation boli count during the EPM test was more with the RF-EMR group. No statistically significant difference was found in total distance travelled, total arm entries, percentage of closed arm entries and parallelism index in the RF-EMR exposed rats compared to controls. Results indicate that mobile phone radiation could affect the emotionality of rats without affecting the general locomotion.

  7. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    Science.gov (United States)

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock.

  8. Metabonomic study of rats exposed to cigarette sidestream smoke

    Institute of Scientific and Technical Information of China (English)

    LIAN Wen-liu; SHI Xian-zhe; LUO Jia; REN Feng-lian

    2016-01-01

    A metabonomic approach was undertaken in order to detect urinary endogenous and exogenous metabolites and to evaluate the effects of passive exposure to cigarette sidestream smoke on rats. Urinary samples from three groups of rats were determined including control rats, rats treated with blended cigarettes (nonmenthol cigarettes) and rats treated with menthol cigarettes. The total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), total 1-hydroxypyrene (1-HOP) and 3-hydroxybenzo[a] pyrene (3-HOBaP) were determined for assessing exposure to cigarette sidestream smoke toxins. Urinary endogenous metabolites in the three groups of rats were also analyzed and the data were processed by chemometrics. Eleven endogenous metabolites were found and identified. Their relative levels were compared among the three groups. The results show that cigarette sidestream smoke has complex effect on rats. Blended cigarette group makes difference to menthol cigarette group in the rats' urinary metabolic changes. Menthol adding to cigarettes has positive and negative effects on rats, respectively. The urinary metabolic profiling of menthol cigarette group is closer to that of control group.

  9. Developmental immunotoxicity of Diazepam in prenatally exposed weanling Wistar rats

    NARCIS (Netherlands)

    Loveren H van; Piersma AH; Jong WH de; Waal EJ de; LPI; LEO; LGM

    1999-01-01

    A prenatal developmental toxicity study was conducted in rats receiving the pharmaceutical Diazepam from gestation days 14 to 20. Reports from the literature claim that Diazepam has impaired the immune function in the offspring of rats receiving treatment during the third trimester of gestation. Dia

  10. Investigation of the protective effect of ellagic acid for preventing kidney injury in rats exposed to nicotine during the fetal period.

    Science.gov (United States)

    Akkoyun, H T; Karadeniz, A

    2016-01-01

    We investigated the possible protective effects of ellagic acid on rat kidneys exposed to nicotine during the fetal period. Twenty pregnant female rats were divided randomly into four groups: control (C), nicotine (N), ellagic acid (EA) and nicotine + ellagic acid (N + EA). Nicotine and ellagic acid treatments were continued throughout the pregnancies and for 15 days after delivery. On day 15, all neonatal pups were sacrificed and their kidneys were removed for biochemical and histopathological examination. The nicotine treatment significantly decreased body weight, total glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and increased malondialdehyde (MDA) and nitric oxide (NO) levels in the N group compared to controls. EA treatment ameliorated decreased body weight, GSH, GSH-Px and SOD activities, and increased MDA and NO levels in group N + EA compared to group N (p kidney damage as shown by incomplete development of glomeruli and Bowman's capsules. Nicotine also caused greater apoptosis in group N compared to group C. Ellagic acid treatment produced histological kidney structure that was closer to normal and it exerted an anti-apoptotic effect in the N + EA group compared to the N group. EA played a protective role against nicotine-induced nephrotoxicity and oxidative stress in rats owing to its antioxidant, radical scavenging and anti-apoptotic effects.

  11. Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.

    Science.gov (United States)

    Thompson, Murray R; Callaghan, Paul D; Hunt, Glenn E; McGregor, Iain S

    2008-05-15

    The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

  12. Temporal Expression of Notch in Preterm Rat Lungs Exposed to Hyperoxia

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To explore the mechanism of Notch in hyperoxia-induced preterm rat lung injury, 2days-old preterm SD rats were randomized into control and hyperoxia group (FiO2 ≥0.85). On day 1, 7, 14 and 21, 8 rat pups of each time point were used to assess histopathological changes of lung with HE staining and to evaluate the expression of Notch1 and Notch3 with immunohistochemistry.Notch1, Notch3, Aquaprin5 (AQP5) and surfactant protein C (SP-C) mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). The results showed that the lung injury in the hyperoxia group was characterized by retarded lung alveolization and differentiation of alveolar epithelial type Ⅱ cells (AEC Ⅱ ). Positive staining of Notch1 in hyperoxia group was weaker than controls at every time point (except for day 7), while positive staining of Notch3 was much stronger (P<0.05, P<0.01). Notch1, Notch3 mRNA level showed similar change as protein level. AQP5, SP C mRNA decreased significantly as compared with that of the controls (P<0.01).We are led to conclude that hyperoxia results in abnormal expression of Notch, which is likely to contribute to the pathogenesis of lung injury through regulating proliferation and transdifferentiation of alveolar epithelial cells.

  13. Forced exercise improves passive avoidance memory in morphine-exposed rats.

    Science.gov (United States)

    Saadipour, K; Sarkaki, A; Alaei, H; Badavi, M; Rahim, F

    2009-09-01

    The aim of this study was to investigate the effect of short-term forced exercise protocol on passive avoidance retention in morphine-exposed rats. Effects of morphine on acquisition and retrieval of retention have been proven in the avoidance paradigms. Twenty four male Wistar rats weighing 250-300 g were used in this study. Animals were randomly divided into four groups including: (1) non-morphine-exposed without exercise (nA.nE) (2) non-morphine-exposed with exercise (nA.E) (3) morphine-exposed without exercise (A.nE) and (4) morphine-exposed with exercise (A.E). Rats ran as forced exercise on the motorized treadmill 1 h daily for ten days. Morphine-exposed animals received intraperitoneal morphine during first 5 days of the exercise period and their dependence to morphine was confirmed by naloxane admistration (10 mg kg(-1), i.p.) and withdrawal test. After 10 days of forced exercise, step down latency was tested and Inflexion Ratio (IR) was evaluated in each rat. Baseline step down latencies before any morphine exposing or exercise have shown no significant alteration in all groups. Inflexion Ratio (IR) ofnA.E group has increased significantly (pexercise on treadmill improved retention in both morphine-exposed and non morphine-exposed rats at least up to 7 days and more than 14 days, respectively. Alteration in retention between exercised groups may attribute the release of adrenal stress hormones such as epinephrine and corticosterone because of the emotional arousal.

  14. Development of sensory motor reflexes in 2 G exposed rats.

    Science.gov (United States)

    Wubbels, Réne; Bouët, Valentine; de Jong, Herman; Gramsbergen, Albert

    2004-07-01

    During gestation and early postnatal development, the animal's size and weight rapidly increase. Within that period, gravity affects sensory and motor development. We studied age-dependent modifications of several types of motor reflexes in 5 groups of rats conceived, born and reared in hypergravity (HG; 2 g). These rats were transferred to normal gravity (NG; 1 g) at various postnatal days, and their behavioral reflexes were compared with a control group which was constantly kept under NG. HG induced a retarded development of vestibular dependent reflexes. Other types of motor behavior were not delayed.

  15. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  16. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

    2016-01-01

    Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

  17. Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

    DEFF Research Database (Denmark)

    Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

    2016-01-01

    Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

  18. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Science.gov (United States)

    Torres-Mendoza, Blanca Miriam; Coronado-Medina, Damharis Elizabeth; Vázquez-Valls, Eduardo; Zamora-Perez, Ana Lourdes; Lemus-Varela, María de Lourdes

    2014-01-01

    The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE), and polychromatic erythrocytes (PCE) in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control), or 0.5 ml of sterile water (negative control). In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses. PMID:24977162

  19. Micronucleated Erythrocytes in Newborn Rats Exposed to Raltegravir Placental Transfer

    Directory of Open Access Journals (Sweden)

    Blanca Miriam Torres-Mendoza

    2014-01-01

    Full Text Available The use of raltegravir in treating HIV/AIDS has been proposed due to its effectiveness in suppressing high loads of HIV RNA in pregnant women, thus preventing infection of the fetus. However, administration of raltegravir during pregnancy produces a compound which is transferred to high concentrations to the offspring. The objective of this study is to evaluate the transplacental genotoxic effect of raltegravir in newborn rats. We evaluated the number of micronucleated erythrocytes (MNE, micronucleated polychromatic erythrocytes (MNPCE, and polychromatic erythrocytes (PCE in the peripheral blood samples of the offspring of Wistar rats treated 6 days before birth with oral administration of raltegravir. The animals were randomly assigned to five groups as follows: raltegravir at doses of 15, 30, or 60 mg/day, cyclophosphamide 10 mg/kg (positive control, or 0.5 ml of sterile water (negative control. In addition, the effect of these drugs on the weight and height of newborns was assessed. There were no differences in the number of MNE, MNPCE, and PCE, and a slight decrease in the weight and height was observed in the offspring of the rat mothers treated with raltegravir. Genotoxicity studies are required in pregnant women to determine the risk of using raltegravir to the fetuses.

  20. Examining maternal influence on OLETF rats' early overweight: insights from a cross-fostering study.

    Science.gov (United States)

    Schroeder, Mariana; Schechter, Michal; Fride, Ester; Moran, Timothy H; Weller, Aron

    2009-05-01

    Obese female Otsuka Long Evans Tokushima Fatty (OLETF) rats display increased nursing time and frequency compared to lean LETO controls, suggesting a maternal contribution to pup preobesity. In previous studies, OLETF pups presented high adiposity, showed greater suckling efficiency, initiative and weight gain from nursing than controls throughout lactation. To further elucidate maternal-infant interactions contributing to pup preobesity, we cross-fostered pups a day after birth and examined maternal behavior. Nursing frequency decreased in OLETF dams raising LETO pups (OdLp) in the third postnatal week, while LETO dams raising OLETF pups showed no significant changes. Fat % was greater in the milk of OLETF versus LETO dams. OdLp pups showed long-term body weight (BW) increase, suggesting that maternal environment can induce BW increases even in the absence of a genetic tendency. Additionally, interaction between OLETF dams and pups produces high nursing frequency, exposing the pups to abundant high-fat milk, thus strengthening their preobese phenotype.

  1. Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

    Science.gov (United States)

    Miranda-Spooner, M; Paccola, C C; Neves, F M O; de Oliva, S U; Miraglia, S M

    2016-03-01

    We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.

  2. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  3. Behaviour-toxicological studies in rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Wurms, F.

    1979-01-01

    Studies were carried out on a behaviour-toxicological animal model in order to find out whether Cd may induce a minimal cerebral dysfunction and whether this effect outlasts prenatal and neonatal exposure. For this purpose, pregnant Wistar rats were given daily s.c. injections of 0.15 mg Cd/kg for a period of 50 d until weaning of the young rats at the age of 4 weeks. The male offspring were either given no Cd until the age of 100 d when the tests were started (A-group), or they were given daily s.c. injections of the above dose (B-group). The third group consisted of NaCl-injected control animals of the same age. The behaviour-toxicological tests were carried out in a Lashley test bench, a swimming labyrinth, and an open field test under blind conditions. Cd concentrations measured in the brain, liver and kidneys at different times during the investigation showed that the placenta-brain barrier or blood-brain barrier was not fully efficient under the experimental conditions. Cd concentrations in neonates were 2.5 times higher in the brain and 5 times higher in the liver and kidneys than in control animals. In both Cd groups, visual discrimination was impaired. In the swimming labyrinth and open field test, significant changes were observed only in B-group rats. Impaired visual differentiation was observed in both groups. However, it is impossible at the present stage of investigation to decide whether the direct Cd lesions are the only cause of these behaviour-toxicological effects.

  4. Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.

    Science.gov (United States)

    Fouad, Amr A; Albuali, Waleed H; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2013-09-01

    The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

  5. Cognitive impairment and neurogenotoxic effects in rats exposed to low-intensity microwave radiation.

    Science.gov (United States)

    Deshmukh, Pravin Suryakantrao; Nasare, Namita; Megha, Kanu; Banerjee, Basu Dev; Ahmed, Rafat Sultana; Singh, Digvijay; Abegaonkar, Mahesh Pandurang; Tripathi, Ashok Kumar; Mediratta, Pramod Kumari

    2015-01-01

    The health hazard of microwave radiation (MWR) has become a recent subject of interest as a result of the enormous increase in mobile phone usage. The present study aimed to investigate the effects of chronic low-intensity microwave exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180 days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at 900 MHz, specific absorption rate (SAR) 5.953 × 10(-4) W/kg; group III: exposed to 1800 MHz, SAR 5.835 × 10(-4) W/kg; and group IV: exposed to 2450 MHz, SAR 6.672 × 10(-4) W/kg. All the rats were tested for cognitive function at the end of the exposure period and were subsequently sacrificed to collect brain. Level of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was assessed using alkaline comet assay in all the groups. The results showed declined cognitive function, elevated HSP70 level, and DNA damage in the brain of microwave-exposed animals. The results indicated that, chronic low-intensity microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous effects on the brain.

  6. Increased bone calcium dissociation in lead-exposed rats

    Directory of Open Access Journals (Sweden)

    Eko Suhartono

    2012-12-01

    Full Text Available Background Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. Methods This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. Results This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (DG > 0 and DH > 0. ConclusionS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (DG > 0 and DH > 0.

  7. Increased bone calcium dissociation in lead-exposed rats

    Directory of Open Access Journals (Sweden)

    Eko Suhartono

    2015-12-01

    Full Text Available BACKGROUND Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. METHODS This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/ kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. RESULTS This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0. CONCLUSIONS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0.

  8. Micronuclei rate and hypoxanthine phosphoribosyl transferase mutation in radon-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Fengmei Cui; Saijun Fan; Mingjiang Hu; Jihua Nie; Hongmei Li; Jian Tong

    2008-01-01

    The genetic changes in rats with radon exposure were studied by the micronucleus technology and detection of hypoxanthine phosphoribosyl transferase (hprt) mutations.The rate of the micronuclei in peripheral blood lymphocytes and tracheal-bronchial epithelial cells in the radon-inhaled rats was higher than that of the controls (P < 0.05).A similar result was obtained from the hprt assay,which showed a higher mutation frequency in radon-exposed rats.Our results suggested that micronuclei rate and hprt deficiency could be used as biomarkers for the genetic changes with radon exposure.

  9. Effects of glutamine pretreatment on learning and memory in heat-exposed rats

    Institute of Scientific and Technical Information of China (English)

    Shenghao Zhao; Lei Wang; Qin Wang; Siyi Wang; Chundi Deng; Xianfei Xie; Youe Yan; Hui Wang

    2008-01-01

    BACKGROUND: Glutamine (Gln) pretreatment can protect neural cells from injuries due to heat, ischemia, hypoxia, endotoxemia, and inflammatory factors.OBJECTIVE: To observe the effects of Gln pretreatment on learning and memory, survival time, and rectal temperature in heat-exposed rats.DESIGN, TIME AND SETTING: The present randomized grouping, neurobehavioral experiment was performed at the Laboratory of Department of Pharmacology, Basic School of Medicine, Wuhan University between March and September 2007.MATERIALS: Twenty-four healthy, Wistar rats were included in this study. SPX-160B biochemistry incubator (Shanghai Experimental Equipment Co., Ltd., China), probe electronic thermometer (11000 type, Maikepai Science and Technology Co., Ltd., China), Y-type maze box used in conjunction with MG-2 maze stimulator (Zhangjiagang Biomedical Instrument Factory, China), L-Gin (Batch No. 061218, 5 g/bottle, prepared into 10% aqueous solution, Amresco Company, USA) were used.METHODS: Twenty-four rats were randomly and evenly divided into 3 groups: heat-exposed, Gln low-lose, and Gln high-dose. Following learning and memory testing with the Y-maze, rats in the heat-exposed group were subjected to heat injury (40.5-41.5℃) in a biochemistry incubator. Rectal temperature was measured every 5 minutes. Thirty-five minutes after heat exposure, rats were removed and placed in the Y-type maze to test learning and memory again. Subsequently, the rats were returned to the same environment of thermal stimulation until they died. Rat survival time was recorded. Subsequent to learning and memory testing, rats in the Gln low-dose and high-dose groups received an i.p. injection of Gln (0.4 g/kg and 0.8 g/kg, respectively), and were exposed to heat injury. The remaining experimental procedures remained the same as for the heat-exposed group.MAIN OUTCOME MEASURES: Rat learning and memory, rectal temperature, and survival time in heat exposure environment.RESULTS: (1) In the Y

  10. The Effect of Hypericum Perforarum on Anxiety and Depressant Activity in Wistar Rats Exposed to Phenol

    Directory of Open Access Journals (Sweden)

    M Modhej

    2015-02-01

    Results: The statistic findings indicated that there were no significant differences between behavior tests with respect to the treatments (P> 0.05. Conclusion: The study results proposed that the used levels of Hypericum Perforarum extract did not show any significant effects on reduction of anxious and depressant behaviors in phenol exposed Wistar rats.

  11. Histopathological changes in Wistar albino rats exposed to aqueous extract of unripe Carica papaya

    Directory of Open Access Journals (Sweden)

    Taofeeq Oduola

    2010-05-01

    Full Text Available Background: Exposure of animals to xenobiotics may or may not trigger adverse response at cellular levels. Aqueous extract of unripe Carica papaya is consumed by sickle cell patients as antisickling agent in Western Nigeria. Aim: This study was undertaken to investigate the effects of Carica papaya on certain organs in Wister albino rats exposed to aqueous extract of unripe Carica papaya. Materials and Methods: Different doses of aqueous extract of unripe Carica papaya were administered orally daily for 42 days to six groups of rats. At the end of exposure, the animals were sacrificed and tissue sections were prepared from livers, kidneys, hearts and small intestines using standard techniques. Results: Histopathological results showed that no pathological changes were observed in tissue sections of experimental animals when compared with tissue sections of the same organs in control animals. Conclusion: No pathological changes were elicited in the organs of rats exposed to aqueous extract of unripe Carica papaya.

  12. Autonomic substrates of the response to pups in male prairie voles.

    Directory of Open Access Journals (Sweden)

    William M Kenkel

    Full Text Available Caregiving by nonparents (alloparenting and fathers is a defining aspect of human social behavior, yet this phenomenon is rare among mammals. Male prairie voles (Microtus ochrogaster spontaneously exhibit high levels of alloparental care, even in the absence of reproductive experience. In previous studies, exposure to a pup was selectively associated with increased activity in oxytocin and vasopressin neurons along with decreased plasma corticosterone. In the present study, physiological, pharmacological and neuroanatomical methods were used to explore the autonomic and behavioral consequences of exposing male prairie voles to a pup. Reproductively naïve, adult male prairie voles were implanted with radiotransmitters used for recording ECG, temperature and activity. Males responded with a sustained increase in heart-rate during pup exposure. This prolonged increase in heart rate was not explained by novelty, locomotion or thermoregulation. Although heart rate was elevated during pup exposure, respiratory sinus arrhythmia (RSA did not differ between these males and males exposed to control stimuli indicating that vagal inhibition of the heart was maintained. Blockade of beta-adrenergic receptors with atenolol abolished the pup-induced heart rate increase, implicating sympathetic activity in the pup-induced increase in heart rate. Blockade of vagal input to the heart delayed the males' approach to the pup. Increased activity in brainstem autonomic regulatory nuclei was also observed in males exposed to pups. Together, these findings suggest that exposure to a pup activates both vagal and sympathetic systems. This unique physiological state (i.e. increased sympathetic excitation of the heart, while maintaining some vagal cardiac tone associated with male caregiving behavior may allow males to both nurture and protect infants.

  13. Aggregation in quads but not pairs of rats exposed to cat odor or bright light.

    Science.gov (United States)

    Bowen, Michael T; Keats, Kirily; Kendig, Michael D; Cakic, Vince; Callaghan, Paul D; McGregor, Iain S

    2012-07-01

    In many prey species aggregation of individuals is a defensive strategy commonly employed in response to predators and predator-related cues. However, very little work has explored this adaptive response in laboratory rats. It is known that individual rats show characteristic defensive responses to predator odors, such as hiding, avoidance, inhibition of foraging, feeding and reproduction, and risk assessment directed toward the odor source. However, whether these species-typical responses in individuals are altered in the presence of other conspecifics is yet to be characterized. The present study therefore examined the defensive response of groups of two rats (dyads) or four rats (quads) to two unconditioned stressors: bright ambient light and cat odor (a 2g ball of cat fur). The dyads and quads were formed from familiar cage mates and test sessions (20 min) occurred in a large open arena (1200 mm(2)) to which the rats had been extensively habituated under dark conditions. The results showed that when quads of rats were exposed to either cat odor or bright light in this arena, they showed characteristic increases in close social proximity, termed "huddling". A tight grouping of 3 (triplet) or 4 (quad) rats was commonly seen in response to cat fur, while triplets were more commonly seen in response to bright light. Interestingly there was no evidence for increased social proximity in dyads exposed to either stressor, only in quads. However, cat odor caused other signs of fear (such as decreased locomotor activity and increased defecation) in both quads and dyads. It is concluded that huddling is a rodent defensive strategy in rats when anxiogenic stimuli are encountered by larger groups of rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Olfactory classical conditioning in neonatal mouse pups using thermal stimuli.

    Science.gov (United States)

    Bollen, Bieke; Matrot, Boris; Ramanantsoa, Nelina; Van den Bergh, Omer; D'Hooge, Rudi; Gallego, Jorge

    2012-04-01

    Mouse models are increasingly used to investigate genetic contributions to developmental disorders in children, especially newborns. In particular, early cognitive assessment in newborn mice is critical to evaluate pediatric drug efficacy and toxicity. Unfortunately, methods for behavioral tests in newborn mice are scarce. Therefore, developing such tests for newborn mice is a priority challenge for neurogenetics and pharmacological research. The aim of the present study was to develop a conditioning method well suited to high-throughput cognitive screening in newborn mice. To this end, we developed an odor-preference conditioning test using ambient temperature as an unconditioned stimulus (US) and artificial odors as conditioned stimuli (CS). First, we showed that mouse pups move toward the thermoneutral temperature when offered a choice between a thermoneutral and cold environment, thus showing thermotaxis. Second, we conducted a classical conditioning paradigm in pups aged six to ten days. In terms of central nervous system development, this period corresponds to extreme prematurity to early post-term period in humans. During acquisition, the pups were alternatively exposed to odor CS paired with either cold or warm temperatures. Immediately after acquisition, the pups underwent a two-odor choice test, which showed preference for the odor previously paired with the warm temperature, thus showing conditioning. The proposed paradigm is easy to conduct, and requires modest experimenter interference. The method is well suited for high-throughput screening of early associative disorders in newborn mice.

  15. Behavior, physiology, and energy deposition in rats chronically exposed to 2450-MHz radiation

    Energy Technology Data Exchange (ETDEWEB)

    D' Andrea, J.A.; Gandhi, O.P.

    1987-11-01

    The research program was initiated to determine both the specific absorption rate (SAR) and the behavioral and physiological consequences of chronic c-w microwave radiation exposure at 2450 MHz in the laboratory rat. Whole-body average and local SARs at discrete sites within the body of rats and mice were determined experimentally using different exposure systems and analytical techniques. The whole-body average SAR and the distribution of SAR within the body depends on a variety of factors: type of exposure system, polarization of the field, size of the animal, and angle of radiation incident on the body. Three experiments were conducted to determine the effects of chronic exposure to 2450-MHz microwave radiation on several measures of rat behavior and physiology. Groups of rats were exposed intermittently to 2450-MHz radiation at power densities of 0.5 mW/sq. cm. or 2.5 mW/sq. cm. for 90 days.

  16. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

    Institute of Scientific and Technical Information of China (English)

    Mohammad Shahandeh; Valiollah Dabidi Roshan; Somayeh Hosseinzadeh; Soleiman Mahjoub; Vaginak Sarkisian

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001), and significantly decreased plasma level of malondialdehyde (P < 0.001). Acute exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

  17. Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?

    Science.gov (United States)

    Ferreira, Cecília S; Carvalho, Kátia C; Maganhin, Carla C; Paiotti, Ana P R; Oshima, Celina T F; Simões, Manuel J; Baracat, Edmund C; Soares, José M

    2016-02-01

    Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

  18. Uterine phenotype of young adult rats exposed to dietary soy or genistein during development.

    Science.gov (United States)

    Eason, Renea R; Till, S Reneé; Velarde, Michael C; Geng, Yan; Chatman, Leon; Gu, Liwei; Badger, Thomas M; Simmen, Frank A; Simmen, Rosalia C M

    2005-10-01

    Dietary soy intake is associated with protection from breast cancer, but questions persist on the potential risks of the major soy isoflavone genistein (GEN) on female reproductive health. Here, we evaluated intermediate markers of cancer risk in uteri of cycling, young adult Sprague-Dawley rats lifetime exposed to one of three AIN-93G semipurified diets: casein (CAS), soy protein isolate (SPI+ with 276 mg GEN aglycone equivalents/kg) and CAS+GEN (GEN at 250 mg/kg). Postnatal day 50 (PND50) rats lifetime exposed to GEN or SPI+ had similar uterine luminal epithelium height, myometrial thickness, endometrial gland numbers, endometrial immunoreactive proliferating cell nuclear antigen (PCNA), and serum estrogen and progesterone, as CAS-fed rats. GEN-fed rats showed modestly increased apoptosis in uterine glandular epithelium, compared to those of CAS- or SPI+-fed groups. Diet had no effect on the uterine expression of genes for the tumor suppressors PTEN, p53 and p21, and the apoptotic-associated proteins Bcl2, Bax and progesterone receptor. Uterine tissue and serum concentrations of total GEN were higher in rats fed GEN than in those fed SPI+. Human Ishikawa endocarcinoma cells treated with GEN-fed rat serum tended to exhibit increased apoptotic status than those treated with CAS-fed rat serum. Exogenously added GEN (0.2 and 2 microM) increased, while estradiol-17beta (0.1 microM) decreased Ishikawa cell apoptosis, relative to untreated cells. Results suggest that lifetime dietary exposure to soy foods does not alter uterine cell phenotype in young adult rats, while GEN, by enhancing uterine endometrial glandular apoptosis in vivo and in vitro, may confer protection against uterine carcinoma. Given its limited influence on uterine phenotype of young adult females, GEN, when taken as part of soy foods or as supplement, should be favorably considered for other potential health benefits.

  19. Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats.

    Science.gov (United States)

    Beaudin, Stéphane A; Stangle, Diane E; Smith, Donald R; Levitsky, David A; Strupp, Barbara J

    2007-01-01

    This study evaluated the efficacy of a 3-week course of succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task). In the RO task, the performance disruption produced by committing an error on the previous trial was significantly greater for both unchelated lead-exposed groups than for controls. The High Pb rats were also more sensitive to reward omission than controls, providing converging evidence for impaired regulation of arousal or emotion. Importantly, succimer treatment was effective in normalizing the heightened reactivity of the lead-exposed animals to both errors and reward omission. In addition, non-lead-exposed rats that were treated with succimer tended to be more affected by a prior error than controls in their latency to respond on post-error trials. In sum, these findings provide new evidence that succimer chelation can significantly lessen the lasting neurobehavioral dysfunction produced by early lead exposure, but also suggest that there may be risks of administering the drug to individuals without elevated blood lead levels.

  20. Thermoregulation in cold- and noncold-acclimated rats cold exposed in hypergravic fields

    Science.gov (United States)

    Horowitz, J. M.; Horwitz, B. A.; Monson, C. B.

    1983-01-01

    The effect of hypergravity on thermoregulation processes is investigated experimentally in rats. Hooded male Long-Evans rats were kept for 6 weeks at 5 or 23 C (cold-acclimated and noncold-acclimated groups, CA and NCA) prior to testing. One test protocol comprised sequential 1-h exposures to 23 C at 1 G, 23 C at 3 G (in a 2.1-m radius centrifuge; -Gx), 8 C at 3 G, 8 C at 1 G, and finally 23 C at 1 G, with continuous measurement of the oxygen consumption. In a second protocol, restrained rats were exposed to 23 C at 1 G, 23 C at 3 G, and 10 C at 3 G, and core temperature changes were monitored. The results are presented in graphs and a table. Oxygen consumption doubled in both CA and NCA rats on exposure to cold at 1 G, but at 3 G NCA consumption decreased while CA consumption remained high. The CA rats were also more able to maintain core temperature at 3 G than the NCA rats. These differences are attributed to the nonshivering thermogenic processes developed in CA rats, which appear to be unaffected by hypergravity.

  1. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens.

    Science.gov (United States)

    Boberg, Julie; Mandrup, Karen Riiber; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Hadrup, Niels; Berthelsen, Line; Elleby, Anders; Kiersgaard, Maria; Vinggaard, Anne Marie; Hass, Ulla; Nellemann, Christine

    2013-09-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold "high human dietary intake" mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol and the isoflavones genistein and daidzein. This mixture induced persistent adverse effects, as adult male mammary glands showed hypertrophic growth. A reduced anogenital distance in newborn males indicated an anti-androgenic mode of action. Testosterone levels, testis and prostate weights, and expression of selected genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels. Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based.

  2. Influence of trans fat on skin damage in first-generation rats exposed to UV radiation.

    Science.gov (United States)

    Barcelos, Raquel Cristine S; Vey, Luciana T; Segat, Hecson Jesser; Benvegnú, Dalila M; Trevizol, Fabíola; Roversi, Karine; Roversi, Katiane; Dias, Verônica T; Dolci, Geisa S; Kuhn, Fábio T; Piccolo, Jaqueline; CristinaVeit, Juliana; Emanuelli, Tatiana; Bürger, Marilise E

    2015-01-01

    The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first-generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12 weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR-induced disorders.

  3. Effects of propoxur on male fertility in wistar rat exposed neonatally

    Directory of Open Access Journals (Sweden)

    Augustave Kenfack

    2014-08-01

    Full Text Available Background: Propoxur is a carbamate pesticide widely used in crop and foodstuff protection. They are known to cause a wide variety of symptoms in animals. Methods: Twenty four young male rats were exposed to 0.00, 1.73, 2.60 and 5.20 mg/kg body weight through oral intubation for 90 days. Results: The testis weight increased significantly (P 0.05 but the percentage of sperm motility decreased significantly (P 0.05 change was observed between the control and treated males for the litter size, viability rate and sex-ratio. Conclusions: Despite the impairment of seminal epithelia and sperm characteristics, male rats orally exposed to the studied doses of propoxur maintained their fertility at the 90th day of treatment. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 898-902

  4. Metaplastic changes of nasal respiratory epithelium in rats exposed to hexamethylphosphoramide (HMPA) by inhalation.

    OpenAIRE

    Lee, K. P.; Trochimowicz, H. J.

    1982-01-01

    Rats exposed by inhalation to hexamethylphosphoramide (HMPA) at concentrations of 50, 100, 400, and 4000 parts per billion (ppb) for 6-24 months revealed nasal tumors and squamous metaplasia with inflammation in the nasal epithelium, but no changes were observed at 10 ppb. The ciliated cells were most susceptible to HMPA, showing degenerative changes, with abnormal cilia and extensive deciliation. The desquamated nasal epithelium was repaired initially by undifferentiated mucus or microvillou...

  5. Chinese green tea ameliorates lung injury in cigarette smoke-exposed rats

    OpenAIRE

    Koo, MWL; Ip, MSM; Man, RYK; Mak, JCW; Chan, KH; Ho, SP; Yeung, SC; So, WHL; Cho, CH; Lam, WK

    2009-01-01

    Background: Epigallocatechin-3-gallate (EGCG), which has been shown to have potent antioxidant effect, comprises 80% of catechins in Chinese green tea. This study was to investigate whether cigarette smoke (CS) exposure would induce lung morphological changes and oxidative stress in the CS-exposed rat model, and whether Chinese green tea (Lung Chen tea with EGCG as its main active ingredient) consumption would alter oxidative stress in sera and lung leading to protection of CS-induced lung da...

  6. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

    DEFF Research Database (Denmark)

    Boberg, Julie; Mandrup, Karen; Jacobsen, Pernille Rosenskjold

    2013-01-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold “high human dietary intake” mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resin....... Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based....

  7. Effect of honey on the reproductive system of male rat offspring exposed to prenatal restraint stress.

    Science.gov (United States)

    Haron, M N; Mohamed, M

    2016-06-01

    Exposure to prenatal stress is associated with impaired reproductive function in male rat offspring. Honey is traditionally used by the Malays for enhancement of fertility. The aim of this study was to determine the effect of honey on reproductive system of male rat offspring exposed to prenatal restraint stress. Dams were divided into four groups (n = 10/group): control, honey, stress and honey + stress groups. Dams from honey and honey + stress groups received oral honey (1.2 g kg(-1) body weight) daily from day 1 of pregnancy, meanwhile dams from stress and honey + stress groups were subjected to restraint stress (three times per day) from day 11 of pregnancy until delivery. At 10 weeks old, each male rat offspring was mated with a regular oestrus cycle female. Male sexual behaviour and reproductive performance were evaluated. Then, male rats were euthanised for assessment on reproductive parameters. Honey supplementation during prenatal restraint stress significantly increased testis and epididymis weights as well as improved the percentages of abnormal spermatozoa and sperm motility in male rat offspring. In conclusion, this study might suggest that supplementation of honey during pregnancy seems to reduce the adverse effects of restraint stress on reproductive organs weight and sperm parameters in male rat offspring.

  8. Trans-resveratrol reduces cardiac oxidative stress in rats exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Melina Hauck

    2015-07-01

    Full Text Available Differences between reactive oxygen species and antioxidant defense system unbalance the redox status. The exposure to cigarette smoke can increase this imbalance. Trans-resveratrol is a polyphenol with great antioxidant action that reduces the oxidative stress. This study investigated the effect of the trans-resveratrol supplementation on the cardiac oxidative stress in rats exposed to cigarette smoke. Male Wistar rats were randomized into four groups: Control Group (CG, Exposure to Smoke Group (ESG, Antioxidant Group (AG and Exposure to Smoke plus Antioxidant Group (ESAG. Animals were exposed to cigarette smoke and supplemented with trans-resveratrol (6.0 mg kg-1 for two months. The lipid peroxidation (TBARS and the enzymatic activity of catalase (CAT were measured in the cardiac muscle. The ESG presented the highest lipid peroxidation level compared with CG (p < 0.001, AG (p < 0.001 and ESAG (p < 0.006. The CAT activity was higher in the AG (p < 0.001 and ESAG (p < 0.001 compared with CG. The ESG presented lower CAT activity compared with the ESAG (p < 0.001. The supplementation of Trans-resveratrol attenuated the cardiac oxidative stress and increased the activity of catalase. Our findings evidenced the cardioprotective effect of trans-resveratrol in rats exposed to cigarette smoke.

  9. Changes in operant behavior of rats exposed to lead at the accepted no-effect level.

    Science.gov (United States)

    Gross-Selbeck, E; Gross-Selbeck, M

    1981-11-01

    After weaning, male and female Wistar rats were fed a daily diet containing 1 g lead acetate/kg food until a level of about 20 micrograms/100 mL blood was obtained. The male rats were subjected to the different behavioral tests, whereas the females were mated to untreated males and further exposed until weaning of the offspring. Behavioral testing of the male offspring was performed between 3 and 4 months of age. General behavior of both groups was tested in the open-field task including locomotion, local movements, and emotionality. The conditioned instrumental behavior was tested in the Skinner box from simple to more complex programs. The blood-lead level was measured by flameless atomic absorption spectrometry. No behavioral changes became apparent in the open-field task and in the preliminary operant training. In the more complex programs (DRH = Differential Reinforcement of High Rates), the rats exposed to lead after weaning showed slight changes of DRH performance. By contrast, in pre- and neonatally exposed animals, DRH performance was significantly increased, although blood-lead levels had returned to normal at the time of testing. A comparison of lead effects in animals to possible effects in man is discussed in this paper, and it is concluded that lead exposure to man at doses which presently are suggested to be innocuous may result in subclinical functional changes of the central nervous system.

  10. Changes in markers of oxidative stress and membrane properties in synaptosomes from rats exposed prenatally to toluene

    DEFF Research Database (Denmark)

    Edelfors, Sven; Hass, Ulla; Hougaard, Karin S.

    2002-01-01

    The present study was undertaken in order to investigate if toluene induced oxidative stress in brains from rats exposed prenatally to 1800 ppm toluene 6 hr/day at days 7-20 during the pregnancy. 35-42 days after birth the rats were killed and synaptosomal fractions were prepared...... for the experiments, Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes...

  11. Effects of taurine on cardiovascular and autonomic nervous functions in cold exposed rats.

    Science.gov (United States)

    Kuwahara, Masayoshi; Kawaguchi, Tomohiro; Ito, Koichi; Tsubone, Hirokazu

    2009-01-01

    Exposure to cold temperature might affect on cardiovascular and autonomic nervous function. Although there are a lot of studies on physiological and pathophysiological responses of taurine, it was poorly understood the effects of taurine on cardiovascular and autonomic nervous function during cold circumstances. Therefore, the purpose of this study was to clarify the possible role of taurine on cardiovascular and autonomic nervous function in rats exposed to cold temperature. For this purpose, heart rate, blood pressure and locomotive activity were recorded from conscious and unrestrained rats using a telemetry system. Moreover, the autonomic nervous function was investigated by power spectral analysis of heart rate variability. After the recovery period of implantation of transmitter, 1% taurine was supplied during experimental period ad libitum. After the 7 days control period, both taurine administrated and control groups of rats were exposed a cold temperature. There were no differences in heart rate, blood pressure and locomotive activity between taurine and control groups before cold exposure. However, parasympathetic nervous function was somewhat predominant in taurine group. Heart rate and blood pressure in both groups increased greatly by cold exposure. Heart rate in taurine group was much higher than that in control group. LF and HF powers were decreased by cold exposure in both groups. Although no differences were observed in LF, decrease of HF in taurine group was greater than that in control group. These results suggested that taurine might provide some reservoir for cardiovascular and autonomic nervous function to cold stress in rats.

  12. Altered spontaneous contractions of the ileum by anesthetic agents in rats exposed to peritonitis

    Institute of Scientific and Technical Information of China (English)

    Cengiz Aydin; Ihsan Bagcivan; Sinan Gursoy; Ahmet Altun; Omer Topcu; Ayhan Koyuncu

    2009-01-01

    AIM: To investigate in vitro effects of propofol, midazolam and dexmedetomidine, which are commonly used anaesthesic or sedatives, on spontaneous contractions of the ileum both in normal rats and those exposed to hyperdynamic peritonitis. METHODS: Spontaneous contractions of isolated ileum muscle segments from sham operated rats and those exposed to peritonitis, were studied in vitro. The amplitude and the frequency of spontaneous contractions of ileum muscle segments were studied after adding dexmetetomidine, propofol, and midazolam to the organ bath in a cumulative manner. Spontaneous contractions in ileum smooth muscle segments were decreased significantly in the peritonitis group compared to the control group ( P<0.05). Dexmedetomidine significantly increased the amplitude and peritonitis groups. The frequency of spontaneous contractions were significantly decreased by propofol Dexmedetomidine and midazolam did not cause significant changes in the number of spontaneous contractions in both control and the peritonitis groups ( P>0.05). CONCLUSION: Propofol, midazolam and dexmedetomidine have various in vitro effects on spontaneous contractions of the rat ileum. While dexmedetomidine augments the spontaneous contraction of the rat ileum, propofol attenuates it. However, the effects of these compounds were parallel in both control and peritonitis groups.

  13. Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    WANG Wen-jing; LU Gan; DING Ning; HUANG Han-peng; DING Wen-xiao; ZHANG Xi-long

    2013-01-01

    Background Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin.Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin.The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH.Methods Thirty-nine healthy male Wistar rats were randomly divided into three groups:normal control (NC),CIH and adiponectin supplement (CIH+Ad) with 13 rats in each.Rats in NC were kept breathing normal air,while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days.Rats in CIH+Ad were given intravenous adiponectin of 10 μg twice a week for 30 successive days.Rats in the NC and CIH were injected with normal saline as a control.After 35 days' CIH exposure,the levels of serum adiponectin and genioglossus contractile properties were compared.Results Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs.2236 ng/ml).Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC.Twitch tension,time to peak tension,half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad.All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds.Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH.Conclusions CIH could lead to hypoadiponectinaemia,impaired genioglossus contractile properties and decreased fatigue resistance in rats.Such changes could be partially offset by supplementation of adiponectin.

  14. The Deterioration Seen in Myelin Related Morphophysiology in Vanadium Exposed Rats is Partially Protected by Concurrent Iron Deficiency.

    Science.gov (United States)

    Usende, Ifukibot Levi; Leitner, Dominque F; Neely, Elizabeth; Connor, James R; Olopade, James O

    2016-08-30

    Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental exposure to vanadium, a transition metal can disrupt this iron homeostasis. We investigated the interaction of iron deficiency and vanadium exposure on the myelination infrastructure and its related neurobehavioural phenotypes, and neurocellular profiles in developing rat brains. Control group (C) dams were fed normal diet while Group 2 (V) dams were fed normal diet and pups were injected with 3mg/kg body weight of sodium metavanadate daily from postnatal day (PND) 1-21. Group 3 (I+V) dams were fed iron deficient diet after delivery and pups injected with 3mg/kg body weight sodium metavanadate from PND1-21. Body and brain weights deteriorated in I+V relative to C and V while neurobehavioral deficit occurred more in V. Whereas immunohistochemical staining shows more astrogliosis and microgliosis indicative of neuroinflammation in I+V, more intense OPCs depletion and hypomyelination were seen in the V, and this was partially protected in I+V. In in vitro studies, vanadium induced glial cells toxicity was partially protected only at the LD 50 dose with the iron chelator, desferroxamine. The data indicate that vanadium promotes myelin damage and iron deficiency in combination with vanadium partially protects this neurotoxicological effects of vanadium.

  15. Thioredoxin and impaired spatial learning and memory in the rats exposed to intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    YANG Xiu-hong; LIU Hui-guo; LIU Xue; CHEN Jun-nan

    2012-01-01

    Background Obstructive sleep apnea (OSA) can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer's disease (AD).Chronic exposure to intermittent hypoxia (IH),such as encountered in OSA,is marked by neurodegenerative changes in rat brain.We investigated the change of thioredoxin (Trx),spatial learning and memory in rats exposed to chronic intermittent hypoxia (CIH).Methods Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups of ten each:a CIH+normal saline (CIH+NS group),a N-acetylcystein-treated CIH (CIH+NAC) group,a sham CIH group (sham CIH+NS),and a sham NAC-treated sham CIH (CIH+NAC) group.Spatial learning and memory in each group was assessed with the Morris water maze.Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue.The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to detect the apoptotic cells of the hippocampus CA1 region.Results ClH-rats showed impaired spatial learning and memory in the Morris water maze,including longer mean latencies for the target platform,reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant.Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus,meanwhile,an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH.The rats,which acted better in the Morris water maze,showed higher levels of the Trx mRNA and protein in the hippocampus;apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels.Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.

  16. Protective Effects of Hydroalcoholic Extract of Nasturtium officinale on Rat Blood Cells Exposed to Arsenic

    Directory of Open Access Journals (Sweden)

    Felor Zargari

    2015-06-01

    Full Text Available Background: Arsenic is one of the most toxic metalloids. Anemia and leukopenia are common results of poisoning with arsenic, which may happen due to a direct hemolytic or cytotoxic effect on blood cells. The aim of this study was to examine the effects of hydroalcoholic extract of Nasturtium officinale on blood cells and antioxidant enzymes in rats exposed to sodium (metaarsenite. Methods: 32 Male Sprague Dawley rats were randomly divided into four groups; Group I (normal healthy rats, Group II (treated with 5.5mg/kg of body weight of NaAsO2, Group III (treated with 500mg/kg of body weight of hydro-alcoholic extract of N. officinale, and Group IV (treated with group II and III supplementations. Blood samples were collected and red blood cell, white blood cell, hematocrit, hemoglobin, platelet, total protein and albumin levels and total antioxidant capacity were measured. Data was analyzed with Mann-Whitney U test. Results: WBC, RBC and Hct were decreased in the rats exposed to NaAsO2 (p<0.05. A significant increase was seen in RBC and Hct after treatment with the plant extract (p<0.05. There was no significant decrease in serum albumin and total protein in the groups exposed to NaAsO2 compared to the group I, but NaAsO2 decreased the total antioxidant capacity, significantly. Conclusion: The Nasturtium officinale extract have protective effect on arsenic-induced damage of blood cells.

  17. Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks

    Energy Technology Data Exchange (ETDEWEB)

    Gagnaire, Francois; Langlais, Cristina; Grossmann, Stephane; Wild, Pascal [Institut National de Recherche et de Securite, Departement Polluants et Sante, Vandoeuvre Cedex (France)

    2007-02-15

    Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene. (orig.)

  18. Bone growth and composition in weanling and mature rats exposed to chronic centrifugation

    Science.gov (United States)

    Keil, L. C.; Evans, J. W.

    1982-01-01

    The primary objective of the study is to determine the effect of continuous exposure to hypergravity on the development and composition of weight-bearing bone. The experimental results are seen to suggest that many, if not all, of the changes observed in bone growth and composition derive from the retarded growth rate of the centrifuged rats. Both centrifuged weanling and mature rats exhibit a significant reduction in femur length and mass. The changes in femur size are more apparent in the weanlings since they are exposed to hypergravity during their most rapid phase of skeletal development. In addition to a slower growth rate, the body mass of the mature and weanling animals is reduced even further by the depletion of body fat. The rapid loss of body fat observed in rats and mice during centrifugation, it is found, can produce a prompt and significant rise in relative femur mass after two weeks of exposure. After adaptation to centrifugation, however, relative femur mass is similar to that of controls at four and eight weeks. At 18 weeks, the centrifuged rats again exhibit an increase in relative femur mass. It is thought that this increase in relative femur mass may be generated by the difference in fat deposition between the 1-G controls and the high-G rats.

  19. Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad; Morsy, Mohamed A

    2013-02-01

    To investigate the potential protective effects of captopril, the angiotensin-converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury. Following successful induction of diabetes, captopril treatment (50 mg/kg/day, p.o.) was applied for 4 weeks, after which bilateral renal ischaemia was induced for 30 min followed by reperfusion for 24 h. Captopril significantly attenuated hyperglycaemia and hypoinsulinaemia in diabetic rats, and significantly reduced the elevations of serum creatinine and aldosterone levels, and renal malondialdehyde, tumour necrosis factor-α and nitric oxide (NO), and prevented the depletion of reduced glutathione caused by I/R in diabetic rats. Histopathological renal tissue damage induced by I/R in diabetic rats was ameliorated by captopril treatment. Immunohistochemical analysis revealed that captopril significantly attenuated the reduction of insulin content in pancreatic islet β-cells, and decreased the I/R-induced expression of inducible NO synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin and heme oxygenase-1 in the kidney tissue of diabetic rats. Captopril represents a potential candidate to reduce the risk of renal injury induced by ischaemia/reperfusion in type 2 diabetes. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.

  20. Dog days of summer: Influences on decision of wolves to move pups

    Science.gov (United States)

    Ausband, David E.; Mitchell, Michael S.; Bassing, Sarah B.; Nordhagen, Matthew; Smith, Douglas W.; Stahler, Daniel R.

    2016-01-01

    For animals that forage widely, protecting young from predation can span relatively long time periods due to the inability of young to travel with and be protected by their parents. Moving relatively immobile young to improve access to important resources, limit detection of concentrated scent by predators, and decrease infestations by ectoparasites can be advantageous. Moving young, however, can also expose them to increased mortality risks (e.g., accidents, getting lost, predation). For group-living animals that live in variable environments and care for young over extended time periods, the influence of biotic factors (e.g., group size, predation risk) and abiotic factors (e.g., temperature and precipitation) on the decision to move young is unknown. We used data from 25 satellite-collared wolves ( Canis lupus ) in Idaho, Montana, and Yellowstone National Park to evaluate how these factors could influence the decision to move pups during the pup-rearing season. We hypothesized that litter size, the number of adults in a group, and perceived predation risk would positively affect the number of times gray wolves moved pups. We further hypothesized that wolves would move their pups more often when it was hot and dry to ensure sufficient access to water. Contrary to our hypothesis, monthly temperature above the 30-year average was negatively related to the number of times wolves moved their pups. Monthly precipitation above the 30-year average, however, was positively related to the amount of time wolves spent at pup-rearing sites after leaving the natal den. We found little relationship between risk of predation (by grizzly bears, humans, or conspecifics) or group and litter sizes and number of times wolves moved their pups. Our findings suggest that abiotic factors most strongly influence the decision of wolves to move pups, although responses to unpredictable biotic events (e.g., a predator encountering pups) cannot be ruled out.

  1. The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart.

    Science.gov (United States)

    Türedi, Sibel; Hancı, Hatice; Topal, Zehra; Ünal, Deniz; Mercantepe, Tolga; Bozkurt, İlyas; Kaya, Haydar; Odacı, Ersan

    2015-01-01

    The growing spread of mobile phone use is raising concerns about the effect on human health of the electromagnetic field (EMF) these devices emit. The purpose of this study was to investigate the effects on rat pup heart tissue of prenatal exposure to a 900 megahertz (MHz) EMF. For this purpose, pregnant rats were divided into experimental and control groups. Experimental group rats were exposed to a 900 MHz EMF (1 h/d) on days 13-21 of pregnancy. Measurements were performed with rats inside the exposure box in order to determine the distribution of EMF intensity. Our measurements showed that pregnant experimental group rats were exposed to a mean electrical field intensity of 13.77 V/m inside the box (0.50 W/m(2)). This study continued with male rat pups obtained from both groups. Pups were sacrificed on postnatal day 21, and the heart tissues were extracted. Malondialdehyde, superoxide dismutase and catalase values were significantly higher in the experimental group rats, while glutathione values were lower. Light microscopy revealed irregularities in heart muscle fibers and apoptotic changes in the experimental group. Electron microscopy revealed crista loss and swelling in the mitochondria, degeneration in myofibrils and structural impairments in Z bands. Our study results suggest that exposure to EMF in the prenatal period causes oxidative stress and histopathological changes in male rat pup heart tissue.

  2. Nuclear phenotype evaluation in skeletal muscle from Wistar rats exposed to low-level lasers

    Science.gov (United States)

    Almeida, L. G.; Sergio, L. P. S.; Vicentini, S. C.; Mencalha, A. L.; Paoli, F.; Fonseca, A. S.

    2017-03-01

    Low-level laser therapy includes devices emitting red and near-infrared radiation with output power below 100 mW. These devices are successfully used for the treatment of injuries and to improve exercise performance based on their biomodulatory effect. Despite the wide use of clinical protocols based on these lasers, the laser-induced effects on DNA are still disputed. Thus, the objective of this study was to investigate chromatin organization, ploidy degrees, and DNA fragmentation in skeletal muscle tissue from Wistar rats exposed to low-level red and infrared lasers. Wistar rats were exposed to low-level red and infrared lasers (25, 50, and 100 J cm-2, 100 mW, continuous-wave emission mode) and, after 24h, samples of this tissue were withdrawn for the analysis of chromatin organization, ploidy degrees, and DNA fragmentation by Feulgen reaction detection of micronucleus, and apoptosis by TUNEL assay. Data obtained show that low-level red and infrared lasers alter geometric and densitometric parameters as well ploidy degree in muscle nuclei from Wistar rats, but do not induce DNA fragmentation, chromatin loss, and apoptosis at fluences taken out from clinical protocols.

  3. Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

    Science.gov (United States)

    KIM, YOUNG OCK; LEE, HWA-YOUNG; WON, HANSOL; NAH, SEONG-SU; LEE, HWA-YOUNG; KIM, HYUNG-KI; KWON, JUN-TACK; KIM, HAK-JAE

    2015-01-01

    The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia. PMID:25394395

  4. Plasma renin is increased in young rats exposed to lead in utero and during nursing

    Energy Technology Data Exchange (ETDEWEB)

    Victery, W.; Vander, A.J.; Schoeps, P.; Germain, C.

    1983-01-01

    Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 5, 25, 100, or 500 ppm Pb (as Pb acetate); they were sacrificed at 1 month of age, at which time their mean blood Pb concentrations were, respectively, approximately 3, 9, 19, 30, and 70 ..mu..g/dl. All Pb-exposed groups sacrificed by decapitation had elevated mean plasma renin activities (PRA), relative to controls. Pentobarbital-anesthesia and laparotomy markedly increased PRA in the 0, 100, and 500 ppm groups, but the increase was significantly less in the 100 ppm group. Renal renin concentration was normal in the 5 and 25 ppm groups, but was significantly increased in the 100 and 500 ppm groups. The ratio of plasma angiotensin II to PRA was normal in the 100 ppm group but significantly reduced in the 500 ppm group. We conclude that exposure of rats to those generally present in human populations stimulates basal renin secretion in 1-month-old rats, but partially inhibits the response to renin-releasing stimuli. The highest dose reduces plasma angiotensin II at any given PRA. These results, taken with previous publications, emphasize that the effects of lead on plasma renin even within a single species are greatly affected by the timing of the exposure.

  5. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

    Directory of Open Access Journals (Sweden)

    Sirintip Chaichalotornkul

    2012-01-01

    Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

  6. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    Science.gov (United States)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  7. Evaluation of Histological Findings of Airways of Rats Exposed to Highly Polluted Indoor Air in Offices

    Directory of Open Access Journals (Sweden)

    Martinsone Žanna

    2016-10-01

    Full Text Available Humans are exposed to chemicals and PM (particulate matter, including ultrafine particles (nanoparticles, mainly through inhalation. This creates a risk to their health. Another effect to exposure is expression of cytokines and their role in lung inflammation and morphpathogenesis. We conducted a pilot project based on testing of realistic exposure scenarios by describing morphological changes of the respiratory tract in Wistar rats (male during a 30-day exposure in office where there was high intensity of printing activities. Tracheal tissue of experimental animals had increasing concentrations of inflammatory interleukin IL-1 and decreasing concentrations of IL-6 and TNF-α. The lungs of the experimental animals tended to show focal infiltration of inflammatory cells, vascular plethora, focal and/or diffuse localisation of lymphatic nodules, and also vascular sclerosis and focal emphysema. The results suggested potential dangerous and adverse effect of poor indoor air quality (particles, including nanoparticles, and chemical compounds on respiratory tract tissue of rats.

  8. Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

    Science.gov (United States)

    Husain, K; Kumar, P; Vijayaraghavan, R; Singh, R; Das Gupta, S

    1993-07-01

    The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

  9. Morphogenesis of nasal tumors in rats exposed to hexamethylphosphoramide by inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.P.; Trochimowicz, H.J.

    1984-02-01

    Hexamethylphosphoramide (HMPA) is used as a solvent, polymerization catalyst and, to some extent, as a deicing additive for jet fuels. Nasal tumors have been induced in rats by inhalation exposure to the compound for 6 to 24 months at concentrations of 50, 100, 400, and 4000 parts per billion (ppb), but not in rats exposed at 10 ppb for 24 months. Most nasal tumors were epidermoid carcinomas and developed from the respiratory epithelium or subepithelial nasal gland, both of which revealed squamous metaplasia or dysplasia in the anterior nasal cavity. The glandular cells appear to play an important role in developing epidermoid carcinomas in the nasal cavity. The ultrastructure of epidermoid carcinomas revealed abundant features of glandular differentiation in the neoplastic squamous cells. The morphological expression of glandular cell metamorphosis in the epidermoid carcinoma included intermediate cells showing both glandular and squamous differentiation, inter- or intracellular lumina, secretory vesicles, and mucus droplets in squamous cells and keratin plates.

  10. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  11. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress

    Science.gov (United States)

    Rowson, Sydney A.; Harrell, Constance S.; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J.; Kelly, Sean D.; Reddy, Renuka; Neigh, Gretchen N.

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  12. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress.

    Science.gov (United States)

    Rowson, Sydney A; Harrell, Constance S; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J; Kelly, Sean D; Reddy, Renuka; Neigh, Gretchen N

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  13. Cytomorphometric changes in hippocampal CA1 neurons exposed to simulated microgravity using rats as model

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    Amit eRanjan

    2014-05-01

    Full Text Available Microgravity and sleep loss lead to cognitive and learning deficits. These behavioral alterations are likely to be associated with cytomorphological changes and loss of neurons. To understand the phenomenon, we exposed rats (225-275g to 14 days simulated microgravity (SMg and compared its effects on CA1 hippocampal neuronal plasticity, with that of normal cage control rats. We observed that the mean area, perimeter, synaptic cleft and length of active zone of CA1 hippocampal neurons significantly decreased while dendritic arborization and number of spines significantly increased in SMg group as compared with controls. The mean thickness of the post synaptic density and total dendritic length remained unaltered. The changes may be a compensatory effect induced by exposure to microgravity; however, the effects may be transient or permanent, which need further study. These findings may be useful for designing effective prevention for those, including the astronauts, exposed to microgravity. Further, subject to confirmation we propose that SMg exposure might be useful for recovery of stroke patients.

  14. Uranium XAFS analysis of kidney from rats exposed to uranium

    Science.gov (United States)

    Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Homma-Takeda, Shino

    2017-01-01

    The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate. PMID:28244440

  15. Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress.

    Science.gov (United States)

    Lin, Pao-Yen; Chang, Alice Y W; Lin, Tsu-Kung

    2014-09-01

    Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4 weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.

  16. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Shuhua; Jin, Yaping; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, College of Public Health, Shenyang, Liaoning (China); Sun, Wenjuan; Wang, Fengzhi [Shenyang Medical College, Department of Preventive Medicine, Shenyang, Liaoning (China)

    2009-06-15

    To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p<0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p<0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex. (orig.)

  17. Early postpartum pup preference is altered by gestational cocaine treatment: associations with infant cues and oxytocin expression in the MPOA.

    Science.gov (United States)

    Lippard, E T Cox; Jarrett, T M; McMurray, M S; Zeskind, P S; Garber, K A; Zoghby, C R; Glaze, K; Tate, W; Johns, J M

    2015-02-01

    Cross-fostering studies suggest cocaine-induced deficits in maternal behavior could be associated with altered behavior of offspring following prenatal cocaine-exposure. Neonatal vocalizations are an important offspring cue facilitating early interactions between dam and rodent pup offspring and have been shown to be altered following prenatal cocaine-exposure. It is unclear how variations in acoustic parameters of USVs impact maternal behavior and the mechanism(s) underlying these processes. The present study examined differences in cocaine-exposed and control rodent dam maternal preference of cocaine-exposed or untreated pups in a dual choice apparatus. Relationship of preference-like behavior with pup USVs and dam oxytocin expression was explored. Gestational cocaine-exposure interfered with preference-like behavior of dams on postpartum day 1 with cocaine-exposure associated with decreased time spent on the cocaine-exposed pup side compared to the control pup side, and decreases in preference-like behavior associated in part with decreased number of USVs being emitted by cocaine-exposed pups. On postpartum day 5, decreased oxytocin expression in the medial preoptic area was associated with altered preference-like behavior in cocaine-exposed dams, including frequency and latency to touch/sniff pups. Results indicate cocaine's effects on the mother-infant relationship is likely synergistic, in that cocaine influences mother and offspring both independently and concertedly and that variations within pup vocalizations and the oxytocin system may be potential mechanism(s) underlying this synergistic relationship during the postpartum period.

  18. Evaluation of reproductive function of female rats exposed to radiofrequency fields (27. 12 MHz) near a shortwave diathermy device

    Energy Technology Data Exchange (ETDEWEB)

    Brown-Woodman, P.D.; Hadley, J.A.; Richardson, L.; Bright, D.; Porter, D.

    1989-04-01

    In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

  19. Effects of High-Butterfat Diet on Embryo Implantation in Female Rats Exposed to Bisphenol A.

    Science.gov (United States)

    Martinez, Alan M; Cheong, Ana; Ying, Jun; Xue, Jingchuan; Kannan, Kurunthachalam; Leung, Yuet-Kin; Thomas, Michael A; Ho, Shuk-Mei

    2015-12-01

    Bisphenol A (BPA) is an endocrine disruptor associated with poor pregnancy outcomes in human and rodents. The effects of butterfat diets on embryo implantation and whether it modifies BPA's actions are currently unknown. We aimed to determine the effects of butterfat diet on embryo implantation success in female rats exposed to an environmentally relevant dose of BPA. Female Sprague-Dawley rats were exposed to dietary butterfat (10% or 39% kcal/kg body weight [BW]) in the presence or absence of BPA (250 μg/kg BW) or ethinylestradiol (0.1 μg/kg BW) shortly before and during pregnancy to assess embryo implantation potentials by preimplantation development and transport, in vitro blastulation, outgrowth, and implantation. On gestational day (GD) 4.5, rats treated with BPA alone had higher serum total BPA level (2.3-3.7 ng/ml). They had more late-stage preimplantation embryos, whereas those receiving high butterfat (HBF) diet had the most advanced-stage embryos; dams cotreated with HBF and BPA had the most number of advanced embryos. BPA markedly delayed embryo transport to the uterus, but neither amount of butterfat had modifying effects. An in vitro implantation assay showed HBF doubled the outgrowth area, with BPA having no effect. In vivo, BPA reduced the number of implanted embryos on GD8, and cotreatment with HBF eliminated this adverse effect. HBF diet overall resulted in more and larger GD8 embryos. This study reveals the implantation disruptive effects of maternal exposure to an environmentally relevant dose of BPA and identifies HBF diet as a modifier of BPA in promoting early embryonic health.

  20. Developmental changes in content of glial marker proteins in rats exposed to protein malnutrition.

    Science.gov (United States)

    Feoli, Ana Maria; Leite, Marina C; Tramontina, Ana Carolina; Tramontina, Francine; Posser, Thais; Rodrigues, Letícia; Swarowsky, Alessandra; Quincozes-Santos, André; Leal, Rodrigo B; Gottfried, Carmem; Perry, Marcos Luiz; Gonçalves, Carlos-Alberto

    2008-01-02

    Pre- and postnatal protein malnutrition (PMN) adversely affects the developing brain in numerous ways, but only a few studies have investigated specific glial parameters. This study aimed to evaluate specific glial changes of rats exposed to pre and postnatal PMN, based on glial fibrillary acidic protein (GFAP) and S100B immunocontents as well as glutamine synthetase (GS), in cerebral cortex, hippocampus, cerebellum and cerebrospinal fluid, on the 2nd, 15th and 60th postnatal days. We found increases in GFAP, S100B and GS in the cerebral cortex at birth, suggesting an astrogliosis. Hippocampus and cerebellum also exhibited this profile at birth. However, a significant interaction between age and diet in postnatal life was observed only in the S100B of the cerebral cortex. No changes in the content of GFAP and S100B and GS activity were found on the 60th postnatal day in malnourished rats. In contrast, following an increase in the levels of S100B in the cerebrospinal fluid, during the early developmental stages, levels remained elevated on the 60th postnatal day. Our data support the concept of astrogliosis at birth, induced by PMN, and involve extracellular-regulated kinase activation. Specific alterations in cerebral cortex emphasize the regional vulnerability of the brain to malnutrition; some alterations were observed only at birth (e.g. GFAP); others were observed on the 2nd and 15th post-natal days (e.g. ERK phosphorylation). Taken together, transient and persistent alterations (e.g. elevated extracellular levels of S100B) suggest some brain damage or a risk of brain diseases in rats exposed to PMN.

  1. Structural characterization of rat ventricular tissue exposed to the smoke of two types of waterpipe

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    Wajdy Al-Awaida

    2015-10-01

    Full Text Available Objective(s:this study focused on the effect of waterpipe smoke exposure toxicity on the structure of albino rat’s ventricular tissue and their recovery. Materials and Methods: Albino rats were divided into three groups: control, flavored, and unflavored. The control group was exposed to normal air while the flavored and unflavored groups were exposed to waterpipe smoke for a period of 90 days. Each group was followed by a period of 90 days of fresh air exposure. Following each period, the ventricular tissue was removed for biochemical and histopathological studies. Results:The ventricular tissues of waterpipe exposed rats showed some degree of separation between cardiac muscle fibers, infiltration of lymphocytes, and congestion of blood vessel. Also, thin cross sections of ventricular cells revealed pleomorphic mitochondria with partially disrupted cristae, partial disruption of the myofibrils, and deposited toxic materials. The unflavored waterpipe has more deleterious effects on heart ventricular tissues than the flavored one. Waterpipe smoke didn't induce apoptosis in the ventricular tissue. We also found very high levels of plasma thiocyanate after exposure to smoke in the flavored and unflavored groups, while the control group showed no increase. After the recovery period, those tissues showed partial recovery. Conclusion: Waterpipe smoke induces structural changes in the heart ventricle tissues, causing a negative impact on the capacity of the cardiac muscle for pumping blood and may lead to heart attack due to accumulation of free radicals and tissue inflammation. Cessation of smoking is important in returning most of these changes to their normal structure.

  2. Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days.

    Science.gov (United States)

    Wang, Hailan; Ichihara, Gaku; Ito, Hidenori; Kato, Kanefusa; Kitoh, Junzoh; Yamada, Tetsuya; Yu, Xiaozhong; Tsuboi, Seiji; Moriyama, Yoshinori; Sakatani, Rie; Shibata, Eiji; Kamijima, Michihiro; Itohara, Seiichiro; Takeuchi, Yasuhiro

    2002-05-01

    1-Bromopropane is used widely as an alternative to ozone-depleting solvents. The neurotoxic effects of this agent have been described in humans and experimental animals. Here we investigated the underlying mechanisms of the neurotoxic effects of 1-bromopropane by examining the initial biochemical changes in the central nervous system. Four groups of 9 Wistar male rats each were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 7 days. At the end of the experiment, the cerebrum, cerebellum, brain stem and lumbar enlargement of the spinal cord were dissected out from each rat (n = 8) for biochemical analyses. Morphological examinations of the nervous system were performed in the remaining rat of each group. 1-Bromopropane dose-dependently decreased neurospecific gamma-enolase, total glutathione, and nonprotein sulfhydryl groups in the cerebrum and cerebellum. Creatine kinase activity decreased dose-dependently in the brain and spinal cord. Histopathological examination showed swelling of preterminal axons in gracile nucleus and degeneration of myelin in peripheral nerves. Our results of low levels of gamma-enolase suggested that 1-bromopropane might primarily cause functional or cellular loss of neurons in the cerebrum and cerebellum. Glutathione depletion or modification to functional proteins containing a sulfhydryl base as a critical site might be the underlying mechanism of 1-bromopropane neurotoxicity.

  3. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

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    Gisele Negro Lima

    2015-02-01

    Full Text Available OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip¯ Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip¯ Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis.

  4. Lead exposure increases oxidative stress in the gastric mucosa of HCI/ethanol-exposed rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the role of reactive oxygen species in the ulcer-aggravating effect of lead in albino rats.METHODS: Albino Wistar rats were randomly divided into three groups and treated orally with 100 mg/L (low dose) or 5000 mg/L (high dose) of lead acetate for 15 wk. A third group received saline and served as control.At the end of wk 15, colorimetric assays were applied to determine the concentrations of total protein and nitrite, the activities of the oxidative enzymes catalase and superoxide dismutase, and lipid peroxidation in homogenized gastric mucosal samples.RESULTS: Exposure of rats to lead significantly increased the gastric mucosal damage caused by acidified ethanol. Although the basal gastric acid secretory rate was not significantly altered, the maximal response of the stomach to histamine was significantly higher in the lead-exposed animals than in the unexposed control group. Exposure to low and high levels of lead significantly increased gastric lipid peroxidation to 183.2% ± 12.7% and 226.1% ± 6.8% of control values respectively (P < 0.0). On the other hand, lead exposure significantly decreased catalase and superoxide dismutase (SOD) activities and the amount of nitrite in gastric mucosal samples.CONCLUSION: Lead increases the formation of gastric ulcers by interfering with the oxidative metabolism in the stomach.

  5. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  6. Changes on fecal microbiota in rats exposed to permethrin during postnatal development.

    Science.gov (United States)

    Nasuti, Cinzia; Coman, Maria Magdalena; Olek, Robert A; Fiorini, Dennis; Verdenelli, Maria Cristina; Cecchini, Cinzia; Silvi, Stefania; Fedeli, Donatella; Gabbianelli, Rosita

    2016-06-01

    Alteration of the gut microbiota through diet and environmental contaminants may disturb the mammalian digestive system, leading to various diseases. Because most exposure to environmentally pyrethroid pesticides such as permethrin (PERM) occurs through the diet, the commensal gut microbiota is likely to be exposed to PERM. The study aimed at evaluating the effect of low-dose exposure to PERM in early life on the composition of fecal microbiota in rats. Over a 4-month follow-up period, fecal microbiota and short-chain fatty acids were measured in order to identify possible differences between PERM-treated rats and controls. Further in vitro antimicrobial experiments were conducted to establish the antibacterial activity of PERM against different strains to obtain Minimal Inhibitory Concentrations. The main finding focused on the reduced abundance of Bacteroides-Prevotella-Porphyromonas species, increased Enterobacteriaceae and Lactobacillus in PERM-treated rats compared to controls. Changes of acetic and propionic acid levels were registered in PERM-treated group. From in vitro studies, PERM showed higher antibacterial activity against beneficial bacteria such as Bifidobacterium and Lactobacillus paracasei, while to inhibit potential pathogens as Staphylococcus aureus and Escherichia coli PERM concentration needed to be increased. In summary, exposure to PERM could affect the fecal microbiota and could be a crucial factor contributing to the development of diseases.

  7. Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride

    Energy Technology Data Exchange (ETDEWEB)

    Di Giusto, Gisela; Torres, Adriana M. [Universidad Nacional de Rosario, CONICET, Area Farmacologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Rosario (Argentina); Anzai, Naohiko; Endou, Hitoshi [Kyorin University School of Medicine, Department of Pharmacology and Toxicology, Tokyo (Japan); Ruiz, Maria L. [Universidad Nacional de Rosario, CONICET, Instituto de Fisiologia Experimental, Facultad de Ciencias Bioquimicas y Farmaceuticas, Rosario (Argentina)

    2009-10-15

    This study was designed to evaluate the expression and function of the organic anion transporters, Oat1 and Oat3, in rats exposed to a nephrotoxic dose of HgCl{sub 2}. Oat1 protein expression increased in renal homogenates and decreased in renal basolateral membranes from HgCl{sub 2} rats, while Oat3 protein abundance decreased in both kidney homogenates and basolateral membranes. The lower protein levels of Oat1 and Oat3 in basolateral membranes explain the lower uptake capacity for p-aminohippurate (in vitro assays) and the diminution of the systemic clearance of this organic anion (in vivo studies) observed in treated rats. Since both transporters mediate mercury access to the renal cells, their down-regulation in basolateral membranes might be a defensive mechanism developed by the cell to protect itself against mercury injury. The pharmacological modulation of the expression and/or the function of Oat1 and Oat3 might be an effective therapeutic strategy for reducing the nephrotoxicity of mercury. (orig.)

  8. Activity of selected antioxidative enzymes in rats exposed to dimethoate and pyrantel tartrate.

    Science.gov (United States)

    Barski, D; Spodniewska, A

    2012-01-01

    This study presents the results of research concerning the effect of single and combined application of pyrantel tartrate and dimethoate on selected antioxidative enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in rat erythrocytes. Pyrantel tartrate was applied twice, at a dose of 85 mg/kg bw at a two week interval, i.e. on day 14 and 28 of the experiment, orally, in a water solution with a stomach tube. Dimethoate was administered with drinking water for 28 days at a dose of 25 mg/kg bw/day. It was found that pyrantel tartrate caused only small changes in the activity of the antioxidative enzymes under analysis. Subchronic exposure of rats to dimethoate caused a significant increase in the activity of CAT, SOD and GPx in erythrocytes, indicating the existence of strong oxidative stress. In combined intoxication, no significant effects of administering pyrantel tartrate on the activity of CAT, SOD and GPx was found in animals poisoned with dimethoate. The profile of changes was similar to that observed in rats exposed only to the organophosphorus insecticide. This may indicate a lack of interaction between the compounds used in the experiment.

  9. N-Butylphthalide Alleviates Blood-Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

    Directory of Open Access Journals (Sweden)

    Mingjun Bi

    2016-10-01

    Full Text Available Carbon monoxide (CO poisoning is one of the most important health concerns and may result in neuropathologic changes and neurologic sequelae. However, few studies have addressed the correlation between CO poisoning and blood-brain barrier (BBB impairment. In this study, we investigated the effects of N-butylphthalide (NBP on the expressions of zonula occludens-1 (ZO-1, claudin-5 and aquaporin-4 (AQP-4 proteins in a CO poisoning rat model. The results indicated that the brain water content was obviously increased, and the tight junctions (TJs between endothelial cells were disrupted, resulting in significant cerebral edema and BBB dysfunction in a rat model of CO poisoning. Meanwhile, the ultrastructure of endothelial cells and pericytes was seriously damaged, and the expressions of ZO-1 and claudin-5 were decreased at an early stage (<7 days. NBP treatment could efficiently maintain the ultrastructural and functional integrity of BBB, alleviate cerebral edema. Besides, NBP could also markedly increase the levels of both ZO-1 and claudin-5 proteins compared with those in rats exposed to CO (P<0.05, whereas NBP had no apparent regulatory effect on AQP-4 expression. Taken together, this study highlights the importance of ZO-1 and claudin-5 proteins in maintaining BBB ultrastructure and function after CO poisoning. NBP, as a novel treatment approach, may effectively inhibit the down-regulation of ZO-1 and claudin-5 proteins (but not AQP-4, thereby preserving the barrier function and reducing cerebral edema after CO poisoning.

  10. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  11. Oral Administration of Ganoderma lucidum to Lead-Exposed Rats Protects Erythrocytes against Hemolysis: Implicates to Anti-Anemia

    Science.gov (United States)

    Hossain, Shahdat; Bhowmick, Sujan; Islam, Saiful; Rozario, Liza; Jahan, Sabrin; Hassan, Mehedi; Sarkar, Marzan; Choudhury, Bazlul Karim; Ahmed, Sohel; Shahjalal, Hussain

    2015-01-01

    We studied the effect of chronic oral exposure to lead acetate (PbA) on the sensitivity of RBC to hemolysis and whether the sensitivity could be decreased by feeding the rats with extract of medicinal mushroom Ganoderma lucidum. Three groups of rats, control, PbA-exposed, and G. lucidum (Gl)+PbA, were used. PbA (3 mM) was administered via drinking water and G. lucidum extract by gavage at 300 mg/Kg BW/day for 12 weeks. Afterwards, the rats were killed and washed RBCs were subjected to hemolysis in the presence of Fenton's reagents. Hemolysis was determined by estimating the amount of released hemoglobin. The levels of lipid peroxide (LPO) and GSH were determined from RBC membranes and whole RBCs, respectively. The levels of TNFα and LPO also were determined from hepatic tissues. The RBCs of PbA-exposed rats displayed significantly higher sensitivity to hemolysis than those of the Gl+PbA rats. The levels of LPO increased and GSH decreased in the RBCs, with concomitant increases in the levels of hepatic TNFα and LPO in the PbA-exposed rats. The degree of hemolysis was significantly low in the RBCs of Gl+PbA rats, concurrently with amelioration of hepatic parameters. Finally, the study suggests that PbA-induced-hemolysis and related oxidative-toxicity might be minimized by consumption of G. lucidum. PMID:26300947

  12. Oral Administration of Ganoderma lucidum to Lead-Exposed Rats Protects Erythrocytes against Hemolysis: Implicates to Anti-Anemia

    Directory of Open Access Journals (Sweden)

    Shahdat Hossain

    2015-01-01

    Full Text Available We studied the effect of chronic oral exposure to lead acetate (PbA on the sensitivity of RBC to hemolysis and whether the sensitivity could be decreased by feeding the rats with extract of medicinal mushroom Ganoderma lucidum. Three groups of rats, control, PbA-exposed, and G. lucidum (Gl+PbA, were used. PbA (3 mM was administered via drinking water and G. lucidum extract by gavage at 300 mg/Kg BW/day for 12 weeks. Afterwards, the rats were killed and washed RBCs were subjected to hemolysis in the presence of Fenton’s reagents. Hemolysis was determined by estimating the amount of released hemoglobin. The levels of lipid peroxide (LPO and GSH were determined from RBC membranes and whole RBCs, respectively. The levels of TNFα and LPO also were determined from hepatic tissues. The RBCs of PbA-exposed rats displayed significantly higher sensitivity to hemolysis than those of the Gl+PbA rats. The levels of LPO increased and GSH decreased in the RBCs, with concomitant increases in the levels of hepatic TNFα and LPO in the PbA-exposed rats. The degree of hemolysis was significantly low in the RBCs of Gl+PbA rats, concurrently with amelioration of hepatic parameters. Finally, the study suggests that PbA-induced-hemolysis and related oxidative-toxicity might be minimized by consumption of G. lucidum.

  13. Alterations of metallothionein isomers in Hg{sup 0}-exposed rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Nagano, M. [Morikawa Kenkodo Co., Ltd., 2170 Taguchi, Kosa, Kamimashiki, Kumamoto 861-4616 (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji, Kumamoto 862-0976 (Japan)

    2003-01-01

    Previously we found that exposure to mercury vapor effectively induced brain metallothionein (MT) in rats. Here, using FPLC-gel chromatography, we examined time-dependent alterations in the MT isomers, MT-I/II and MT-III, following 3 weeks of exposure. Rats were exposed to mercury vapor at 8.3 mg/m{sup 3} for 15 h in total over 5 consecutive days. Total MT levels in rat cerebrum and cerebellum increased by 65% and 155%, respectively, 24 h after the final exposure. The increased levels in both tissues remained unchanged for at least 2 weeks after termination of exposure. Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10%. Through mercury vapor exposure, MT-I/II was quickly induced to a significant extent in both tissues, reaching a level comparable to that of MT-III. The induction rate of MT-I/II in the cerebellum was somewhat higher than in the cerebrum. Chromatograms showed that the MT-I/II thus induced began to decline at an early stage in both tissues. In the cerebrum, the amount of MT-I/II on day 22 was about 30% of the maximum level on day 1. On the other hand, the induction of MT-III was not that dramatic, but it did become evident, at least in the latter stage, when MT-I/II had begun to decrease. Thus, though the induction rate of MT-III was not as high as MT-I/II, it was sustained throughout the experimental period. (orig.)

  14. Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats.

    Science.gov (United States)

    Sanchez-Gonzalez, Cristina; Bermudez-Peña, Carmen; Trenzado, Cristina E; Goenaga-Infante, Heidi; Montes-Bayon, María; Sanz-Medel, Alfredo; Llopis, Juan

    2012-08-01

    Vanadium is an element whose role as a micronutrient for humans is not yet completely established, but which has been shown to possess hypoglycaemic properties in diabetes. In an earlier study, we showed that in STZ-diabetic rats, exposure to 1 mg V per day has no effect on glycaemia or on antioxidant status. When the exposure was raised to 3 mg V per day there was a hypoglycaemic effect, together with reduced Se in the tissues, which reduced antioxidant defences. The aim of the present study was to examine whether exposure to 1 mg V per day modifies Se nutritional status and/or antioxidant defences in healthy rats. Two groups of rats were examined: control and vanadium-treated. Vanadium, as bis(maltolato)oxovanadium(iv), was supplied in the drinking water. The experiment had a duration of five weeks. Selenium was measured in excreta, serum, skeletal muscle, kidneys, liver, heart, femur and adipose tissue. Number of red (RBC) and white (WBC) blood cells and haemoglobin (Hb) were determined in samples of whole blood. Glutathione peroxidase (GPx), glutathione transferase (GST), catalase (CAT) and NAD(P)H:quinine-oxidoreductase1 (NQO1) activity, and malondialdehyde (MDA) in the liver were evaluated. Treatment significantly reduced food intake, produced an anaemic state, and decreased Se absorption and Se content in serum, kidneys and the liver. GPx, GST and NQO1 activity were decreased in the liver, while MDA levels rose. We conclude that healthy rats are more sensitive than diabetic ones to the effects of V. This should be taken into account for populations that are particularly exposed to V for environmental reasons, and/or that consume V as a nutritional supplement.

  15. 3. Impact of altered gravity on CNS development and behavior in male and female rats

    Science.gov (United States)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

  16. Epidermal growth factor and lung development in the offspring of the diabetic rat

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    2000-01-01

    Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining...

  17. Dental Fluorosis and Catalase Immunoreactivity of the Brain Tissues in Rats Exposed to High Fluoride Pre- and Postnatally.

    Science.gov (United States)

    Güner, Şirin; Uyar-Bozkurt, Süheyla; Haznedaroğlu, Eda; Menteş, Ali

    2016-11-01

    This study evaluated dental fluorosis of the incisors and immunoreactivity in the brain tissues of rats given chronic fluoride doses pre- and postnatally. Female rats were given drinking water with 0, 30 or 100 ppm fluoride ad libitum throughout gestation and the nursing period. In addition, 63 male offspring were treated with the same water regimens as the mothers after weaning and were followed for 1, 3 or 5 months. The upper and lower incisors were collected, and all teeth were examined under a stereomicroscope and scored by two blinded examiners using a modified rodent enamel fluorosis index. Cortical, hippocampal and cerebellar brain samples were evaluated morphologically and immunohistochemically. All fluoride-treated pups were born with low body weight (p = 0.001). All animals from the fluoride groups had enamel fluorosis with defects of various degrees. The increase in the dental fluorosis scores in the fluoride treatment groups was significant (p fluoride groups was significantly higher than that in the controls after 1, 3 and 5 months (p fluoride.

  18. Effect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stress

    Directory of Open Access Journals (Sweden)

    Ghasem Saki

    2013-01-01

    Full Text Available The aims of this study were to evaluate the effects of administration of Vitamins C and E on fertilization capacity in rats exposed to noise stress. 40 adult male rats were randomly divided into 5 equal groups. Group 1 as controls who were not exposed to noise and groups 2-5 exposed to noise with 90-120 dB intensity and 300-350 Hz frequency from 7 pm to 7 am everyday for 50 days. Group 2 exposed to noise and did not receive Vitamins. Group 3 received vitamin C, Group 4 received Vitamin E. Group 5 received Vitamins C and E concomitantly. After 50 days, serum Follicle-stimulating hormone (FSH, Luteinizing hormone (LH and testosterone were calculated. Then each rat was left with three female rats for mating. Pregnant females were sacrificed on the 19 th day of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The level of FSH, LH and testosterone significantly decreased in rats exposed to noise (P < 0.05. By administration of Vitamins in groups 3-5 we observed that the level of hormones significantly increased in compared to group 2 (P < 0.05. The fertilization capacity of male rats in groups 3-5 significantly increased in compared to group 2 (P < 0.05. There was significant difference between groups 1 and 2 in case of fertilization capacity (P = 0.001. The data in this study strongly suggests a negative role for noise stress on level of FSH, LH and testosterone level and also fertilization capacity of male rats. To complement the information it is suggested that this research be done on human samples.

  19. Generational reproductive outcomes in Wistar rats maternally exposed to Ricinus communis oil at different stages of gestation.

    Science.gov (United States)

    Salami, S A; Raji, Y

    2015-10-01

    Fetal programming hypothesis presupposes that stimulus or insult acting during critical periods of uterine growth and development may permanently alter tissue structure and function. Ricinus communis oil (RCO) has been reported to possess/used as laxative, labor-inducing and estrogenic properties. Generational reproductive effects of maternal exposure to RCO was investigated in rats. A total of 25 pregnant rats randomly assigned to five equal groups were treated with distilled water (control, group 1), RCO (950 mg/kg p.o.) during gestation days (GD) 1-7, 7-14, 14-21 and 1-21, respectively. Birth weight, morphometric data, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile, organ weight and histopathology were determined in the first (F1) and second (F2) filial generations. Results showed a significant decrease (P<0.05) in birth weight/morphometric data in male pups from the GD 1-7 and 7-14 groups. AGD decreased significantly in RCO-treated F1 males. Pubertal age of F1 females decreased significantly (P<0.05) compared with controls. At postnatal day 90, F1 males from the RCO-treated group showed significant decrease in testis weight, body weight, sperm count, motility and normal morphology. Testosterone levels were significantly decreased in RCO-treated F1 males, which also showed testicular interstitial edema and epididymal hypospermia. Only pubertal indexes were altered in F2 rats. Maternal exposure to RCO at early gestation periods impaired androgen-mediated reproductive end points in the first generation of rats. RCO exhibits endocrine disrupting capabilities.

  20. EFFECT OF POSTNATAL EXPOSURE TO N-NITROSODIETHYLAMINE ON THE MYENTERIC PLEXUS OF RAT

    Directory of Open Access Journals (Sweden)

    A. K. Shreevastava

    2015-12-01

    Full Text Available Background: Humans are continuously exposed to the different types of nitrosamines found in the diet, drinking water, tobacco smoking, and work place. These are the potential source of exposure in the present population. Nitrosamines are found mainly in cured meat products, smoked preserved foods, beer, whiskey, pickled and salty preserved food materials. Nitrosamines have cytotoxic, carcinogenic and mutagenic properties. Nitrosamines exert toxic or mutagenic effects by promoting DNA damage, oxidative stress and reactive oxygen species formation that causes increased lipid peroxidation, adduct formation, and pro-inflammatory cytokine activation. Increased chronic exposure of low doses of nitrosamines is unavoidable in current environmental conditions. Important nitrosamines are N-Nitrosodiethylamine (NDEA, N-Nitrosodimethylamine (NDMA, N-Nitrosomorpholine (NMOR, N-Nitrosopyrrolidine (NPYR etc. The nitrosamine explored in this study is N-Nitrosodiethylamine (NDEA, representing environmentally significant nitrosamine. Aim: To study the effect of postnatal exposure to N- Nitrosodiethylamine (NDEA on the myenteric plexus of wistar rat. Materials and Methods: The present study was conducted on pups of wistar rats, (Rattus norvergicus. Six pregnant wistar rats having same pregnancy time were taken. After delivery sixteen pups were chosen randomly. The control and the experimental groups had eight pups each. Sterile water and NDEA were given as 0.2mg/kg intraperitonea daily to the control and the experimental groups of rat pups respectively, from postnatal day 1 to postnatal day 20. All the rat pups were sacrificed on postnatal day 21 to obtain the tissues of the gastrointestinal tract. Results: A significant reduction of morphometric parameters such as the area, the perimeter and the ferret diameter of the perikaryon of the myenteric neurons of the experimental group found .The number of the myenteric neurons per unit area of muscularis externa was

  1. [An immunocytochemical study of the C-cell function of the thyroid in rats exposed on the Kosmos-2044 biosatellite].

    Science.gov (United States)

    Loginov, V I

    1993-01-01

    Immunocytochemical analysis of thyroid gland C-cells of the rats exposed to a 14-day space flight revealed a decrease in the number of C-cells, volume of their nuclei and a declined percentage of active secretory C-cells, which point to a decline of calcitonin proactive and calcitonin secretory hypofunction of the thyroid C-cells system in flown rats. Tail suspension as a microgravity model caused similar changes in C-cells.

  2. 孕期苯乙基异硫氰酸盐染毒对大鼠子代神经行为发育的影响%Changes on neurobehavioral development of the offspring in rats prenataly exposed by phenethyl isothiocyanate

    Institute of Scientific and Technical Information of China (English)

    支媛; 刘海波; 耿桂英; 于洲; 徐海滨

    2011-01-01

    目的 研究大鼠孕期暴露于苯乙基异硫氰酸盐(PEITC)对子一代(F1)神经发育、早期行为及学习记忆能力等的影响.方法 受孕大鼠于孕7~16天分别经口给予0、15、60和120mg/kg PEITC后,观察F1代断崖回避、平面翻正、前肢悬挂、听觉惊愕和嗅觉定位等早期行为发育指标的变化,并应用Y迷宫评价仔鼠学习记忆能力,对F1代大鼠大脑海马区神经元发育情况进行病理学检查.结果 孕大鼠60和120mg/kg染毒剂量组,其F1代仔鼠平面翻正、断崖回避以及嗅觉定向等早期行为指标发育延迟,且运动学习能力下降;120mg/kg染毒剂量组F1代仔鼠海马区平均神经元密度为142±6.7,与阴性对照组相比有显著差异(P<0.05),且神经元损伤评分增至0~1级.结论 大鼠孕期给予PEITC,可对F1代大鼠早期行为和学习记忆产生抑制和干扰;PEITC在15mg/kg剂量条件下无神经发育毒性和行为致畸作用.%Objective To study the effect of rats prenatal exposed to phenethyl isothiocyanate (PEITC) on the postnatal growth and neurobehavioral development of rats. Methods Pregnant adult rats were randomly assigned to 4 groups, of which 3 groups were exposed to PEITC at doses of 15,60 and 120 mg/kg respectively from the 7th to 16th day of gestation, and their Fl pups were observed the impact of PEITC on the age acquisition of two reflexes (cliff avoidance,surface righting) and sensuous function(auditory startle and olfactory discrimination), movement and coordination functions (forelimb hanging) and learning and memory( Y-maze test). Fl pups' brain tissues were taken and neuronal morphology changes were observed with pathology staining. Results Compared to the control group,60 and 120mg/kg groups exposed inuterus caused the Fl rat pups' cliff avoidance, surface righting and olfactory discrimination development delaying,and their learning and memory abilities were impaired. The increase to 0 - 1 level in histological grades

  3. Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane.

    Science.gov (United States)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Takahashi, Masahide; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik; Wang, Yun; Ichihara, Gaku

    2011-11-15

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p<0.05; fold change ≥ ± 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system.

  4. Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

    Directory of Open Access Journals (Sweden)

    Adelisandra S. S. Castelhano

    2013-05-01

    Full Text Available Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of status epilepticus (SE by pilocarpine injection (380 mg/kg, i.p. and control animals received saline (0.9 %, 0,1mL/10 g. It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal status epilepticus in rodents leads to altered anxiety-related and abnormal social behaviors.

  5. Sulindac attenuates valproic acid-induced oxidative stress levels in primary cultured cortical neurons and ameliorates repetitive/stereotypic-like movement disorders in Wistar rats prenatally exposed to valproic acid.

    Science.gov (United States)

    Zhang, Yinghua; Yang, Cailing; Yuan, Guoyan; Wang, Zhongping; Cui, Weigang; Li, Ruixi

    2015-01-01

    Accumulating evidence suggests that anti-inflammatory agents and antioxidants have neuroprotective properties and may be beneficial in the treatment of neurodevelopental disorders, such as autism. In the present study, the possible neuroprotective properties of sulindac, a non-steroidal anti-inflammatory drug (NSAID), were investigated in vitro using cultured cortical neurons with valproic acid (VPA)-induced neurotoxicity, as well as in vivo through the behavioral analysis of rats prenatally exposed to VPA as a model of autism. VPA induced 4-hydroxynonenal (4-HNE) expression, reactive oxygen species (ROS) generation and decreased cell viability in primary cultured cortical neurons established from timed-pregnant (embryonic day 18) Wistar rat pups. However, co-incubation of the neurons with VPA and sulindac reduced oxidative stress and increased cell viability. The rats were administered an intraperitoneal injection with one of the following: VPA, sulindac, VPA and sulindac, or physiological saline, and their offspring were subjected to the open field test. During the test trials, repetitive/stereotypic-like movements for each rat were recorded and analyzed. The results revealed that treatment with both sulindac and VPA reduced the VPA-induced repetitive/stereotypic-like activity and the sulindac and VPA-treated animals responded better in the open field test compared to the VPA-treated animals. The results from the present study demonstrate that the antioxidant properties of sulindac may prove to be beneficial in the treatment of autism, suggesting that the upregulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and facilitates susceptibility to autism.

  6. Parallel assessment of male reproductive function in workers and wild rats exposed to pesticides in banana plantations in Guadeloupe.

    Science.gov (United States)

    Multigner, Luc; Kadhel, Philippe; Pascal, Michel; Huc-Terki, Farida; Kercret, Henri; Massart, Catherine; Janky, Eustase; Auger, Jacques; Jégou, Bernard

    2008-07-30

    There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations. A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans. No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats. Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.

  7. PROTECTIVE EFFECT OF LORANTHUS LONGIFLORUS ON LEARNING AND MEMORY OF RATS EXPOSED TO ELECTROMAGNETIC RADIATION (EMR

    Directory of Open Access Journals (Sweden)

    Hemant Nagar

    2013-06-01

    Full Text Available The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR with the brain is a serious concern of our society. In this study, we aimed to experiment on the antioxidative property of a parasitic plant Loranthus longiflorus (Loranthaceae to protect central nervous system against oxidative damages of mobile phone electromagnetic radiation (EMR. Healthy male albino wistar rats were exposed to RF-EMR by giving 5 min calling/ 5min interval for 1 hour per day for two month, Keeping a GSM (0.9 GHz/1.8 GHz mobile phone in Silent mode (no ring tone in the cage. After 15, 30, 45, 60 days exposure, three randomly picked animals from both groups were tested with using Morris water maze. Antioxidant compounds and their Neuroprotective action of Loranthus longiflorus bark sample collected from Ficus religiosa host trees were assessed. Rats which have been feed with Ethyl acetate Extract of Loranthus longiflorus (EAL bark (700mg/kg body weight, p.o.

  8. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2006-02-16

    Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

  9. [Effects of carbocisteine on airway inflammation and related events in SO2-exposed rats].

    Science.gov (United States)

    Ishibashi, Y; Okamura, T; Masumoto, Y; Tachiiri, T; Momo, K

    2001-01-01

    Airway inflammation leads to secretion of abnormal mucous glycoprotein and ciliary injury. To investigate the possible usefulness of carbocisteine against airway inflammation and events related to it, we conducted a study in SO2-exposed rats of the effects of carbocisteine and ambroxol, as an active control drug, on components of mucous glycoprotein (fucose, sialic acid and protein) in bronchoalveolar lavage fluid (BALF); on infiltration and activation of inflammatory cells in BALF; on tracheal and bronchial-ciliary lesions; and on cAMP levels in tracheal and alveolar tissues. Carbocisteine inhibited or improved all SO2-induced changes tested, and dosages of 125 and 250 mg/kg b.i.d. reduced fucose, sialic acid and protein contents, inflammatory cells (as markers of inflammation), free radicals, and elastase activity in BALF, and suppressed the development of ciliary lesions of the tracheal and bronchial mucosa, while ambroxol (10 mg/kg b.i.d.) showed no such effects. In addition, carbocisteine improved cAMP levels in the tracheal and alveolar tissues. These results indicate that carbocisteine is able to prevent the development of inflammation-related respiratory disease in this rat model, and that this remission of airway inflammation may be associated with carbocisteine-induced normalization of cAMP levels in tracheal and alveolar tissues as well as with its mucoregulant and anti-inflammatory effects. In conclusion, carbocisteine has a unique mucoregulant action and inhibits SO2-induced airway inflammation in a manner different from that of ambroxol.

  10. Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

    Science.gov (United States)

    Fokos, S; Panagis, G

    2010-05-01

    Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behaviour, the reinforcing attributes of these subjective effects are difficult to define in experimental animals. The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats. Male rats were exposed to either 10 days of CUS or no stressor. Alterations in brain reward function were assessed with the intracranial self-stimulation (ICSS) paradigm, and anxiety responses were measured with the elevated plus maze. CUS did not affect baseline brain stimulation reward thresholds. Delta(9)-THC did not exhibit reinforcing actions in the ICSS paradigm neither in nonstressed nor in stressed animals. More importantly, in nonstressed animals, both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects. In stressed animals, however, only the high dose of THC induced an anxiolytic-like response, whereas the low dose induced anxiogenic effects. The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals, and indicate that environmental conditions, such as stressful experiences, do not alter the behavioural effects of Delta( 9)-THC in the ICSS paradigm.

  11. Induction of a heat shock response (HSP 72) in rat embryos exposed to selected chemical teratogens.

    Science.gov (United States)

    Mirkes, P E; Doggett, B; Cornel, L

    1994-02-01

    A monoclonal antibody to the 72 kD heat shock protein (HSP 72), Western blot analysis and 2-D gel electrophoresis/autoradiography were used to determine whether selected chemical teratogens induced the synthesis and accumulation of HSP 72 in postimplantation rat embryos exposed in vitro. The chemical teratogens studied include N-Acetoxy-2-acetylaminofluorene (N-Ac-AAF), cadmium chloride (CAD), cyclophosphamide (CP), sodium arsenite (AS), and sodium salicylate (SAL). Exposures to test chemicals were selected that produced obvious embryotoxicity characterized by abnormal development and growth retardation. Of the five chemical teratogens studied, AS and SAL induced the synthesis and accumulation of HSP 72 in day 10 rat embryos. The kinetics of HSP 72 accumulation, however, differed between AS- and SAL-treated embryos. Maximal levels of HSP 72 were observed 24 hours after AS exposure and 10 hours after SAL exposure. N-Ac-AAF, CD, and CP induced obvious embryotoxicity; however, none of these chemical teratogens induced HSP 72 at any of the timepoints assayed. Although only a small sample of chemical teratogens was studied, our results suggest that the heat shock response, characterized by the synthesis and accumulation of HSP 72, is not a general biomarker for chemical teratogens.

  12. Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats.

    Science.gov (United States)

    Nirujogi, Raja Sekhar; Wright, James D; Manda, Srikanth S; Zhong, Jun; Na, Chan Hyun; Meyerhoff, James; Benton, Bernard; Jabbour, Rabih; Willis, Kristen; Kim, Min-Sik; Pandey, Akhilesh; Sekowski, Jennifer W

    2015-01-01

    To gain insights into the toxicity induced by the nerve agent VX, an MS-based phosphoproteomic analysis was carried out on the piriform cortex region of brains from VX-treated rats. Using isobaric tag based TMT labeling followed by titanium dioxide enrichment strategy, we identified 9975 unique phosphosites derived from 3287 phosphoproteins. Temporal changes in the phosphorylation status of peptides were observed over a time period of 24 h in rats exposed to a 1× LD50, intravenous (i.v.) dose with the most notable changes occurring at the 1 h postexposure time point. Five major functional classes of proteins exhibited changes in their phosphorylation status: (i) ion channels/transporters, including ATPases, (ii) kinases/phosphatases, (iii) GTPases, (iv) structural proteins, and (v) transcriptional regulatory proteins. This study is the first quantitative phosphoproteomic analysis of VX toxicity in the brain. Understanding the toxicity and compensatory signaling mechanisms will improve the understanding of the complex toxicity of VX in the brain and aid in the elucidation of novel molecular targets that would be important for development of improved countermeasures. All MS data have been deposited in the ProteomeXchange with identifier PXD001184 (http://proteomecentral.proteomexchange.org/dataset/PXD001184).

  13. Glutathione and glutathione-related enzymes in rats exposed to dimethoate and/or pyrantel.

    Science.gov (United States)

    Spodniewska, A

    2014-01-01

    The study was undertaken to examine the effect of single and combined administration of dimethoate (an OP insecticide) and pyrantel embonate (an anthelmintic agent) on the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx) and glutathione reductase (GR) in rats. Dimethoate (Group I) was administered to rats at a dose of 1/10 LD50 for 5 consecutive days and pyrantel embonate (Group II) at a dose of 1/5 LD50 for 3 consecutive days. The animals of group III were given both of the mentioned above compounds in the same manner as group I and II, but pyrantel embonate was applied on day 3, 4, and 5 from the beginning of dimethoate intoxication. Material from 6 rats randomly selected from each group was obtained after 3, 6 and 12 hours and 2, 7 and 14 days following the last applied dose of the compounds under study. It was found that application of pyrantel embonate caused only slight changes in the analysed parameters i.e. GSH, GPx and GR. Dimethoate administration caused disturbances in the antioxidative system manifested as a decrease in GSH concentration in the liver (max.--37.7% after 6 hours) and an increase of GPx and GR activities in erythrocytes (max.--21.7% and 29.6% after 3 hours, respectively), compared to the control group. The profile of changes after combined intoxication was similar, but their intensity was higher compared to the group of animals exposed to dimethoate only. Based on current studies, it was concluded that both dimethoate and pyrantel embonate at the applied doses showed a pro-oxidative activity.

  14. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

    Directory of Open Access Journals (Sweden)

    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  15. Assessment of physical traits of rat offspring derived from mothers exposed to dioxin.

    Science.gov (United States)

    Rosińczuk, Joanna; Całkosiński, Ireneusz

    2015-09-01

    Negative effects of dioxin action are associated with limited abilities of their bio-degradation along with continuously increasing production and long-term bio-accumulation of those toxins in living organisms. Dioxins penetrate through placenta to fetus indicating indirect toxic effects on offspring of mothers exposed to the action of these toxins. During lactation a significant part of dioxins is excreted from organism with milk, which contributes to further accumulation of those compounds and multiple exceeding of maximal permissible dose of dioxins in newborns feeding with mother's milk. The aim of the study was to determine how a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administered to females 3 weeks before getting pregnant affects the parturition duration, labour delay, number and weight of offspring. The studies were performed on rat offspring deriving from primigravida females from the Buffalo strain, which 3 weeks before getting pregnant were administered with a single dose of TCDD. The obtained results revealed that labours in females exposed to dioxin effects were characterized by significant temporal range and their end occurred 3 weeks later compared to females from the control group, which gave birth within a very narrow temporal range ending within 2 days. Offspring obtained from females exposed to the TCDD action was smaller in number and was characterized by smaller rearing and smaller birth weight even after the first month of life; however weight gain in both groups was similar and it was twelve-fold increase. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Toxicology, Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510-300 (China); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Takahashi, Masahide [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Wang, Yun [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Gaku, E-mail: gak@med.nagoya-u.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan)

    2011-11-15

    1-Bromopropane (1-BP) is a compound used as an alternative to ozone-depleting solvents and is neurotoxic both in experimental animals and human. However, the molecular mechanisms of the neurotoxic effects of 1-BP are not well known. To identify the molecular mechanisms of 1-BP-induced neurotoxicity, we analyzed quantitatively changes in protein expression in the hippocampus of rats exposed to 1-BP. Male F344 rats were exposed to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks by inhalation. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) were conducted to detect and identify protein modification. Changes in selected proteins were further confirmed by western blot. 2D-DIGE identified 26 proteins with consistently altered model (increase or decrease after both 1- and 4-week 1-BP exposures) and significant changes in their levels (p < 0.05; fold change {>=} {+-} 1.2) at least at one exposure level or more compared with the corresponding controls. Of these proteins, 19 were identified by MALDI-TOF-TOF/MS. Linear regression analysis of 1-BP exposure level identified 8 differentially expressed proteins altered in a dose-dependent manner both in 1- and 4-week exposure experiments. The identified proteins could be categorized into diverse functional classes such as nucleocytoplasmic transport, immunity and defense, energy metabolism, ubiquitination-proteasome pathway, neurotransmitter and purine metabolism. Overall, the results suggest that 1-BP-induced hippocampal damage involves oxidative stress, loss of ATP production, neurotransmitter dysfunction and inhibition of ubiquitination-proteasome system. -- Highlights: Black-Right-Pointing-Pointer 1-BP modified hippocampal proteome in rat and 19 altered proteins were identified. Black-Right-Pointing-Pointer Expression of Ran, TPI, HSP60, PSMA1, ECH1, TPI, B-CK and DJ-1 was changed by 1-BP. Black

  17. Rats reproduce and rear litters during chronic exposure to 150-kV/m, 60-Hz electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Rommereim, D.N.; Kaune, W.T.; Anderson, L.E.; Sikov, M.R. (Battelle, Pacific Northwest Laboratories, Richland, WA (USA))

    1989-01-01

    Mature female rats and their subsequent litters were exposed either to 112- or to 150-kV/m, 60-Hz electric fields or sham-exposed for 19 h daily through pre-breeding, breeding, and rearing periods of experimentation. Exposed females mated in equal percentages and reared litters of equal numbers, and mean body masses of pups were the same as those of sham-exposed animals. Thus, experiments to investigate electric-field effects on reproduction and development in rats are feasible at effective field strengths of 112 and 150 kV/m.

  18. The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nekvasil, N.; Baggio, C. (St. Mary' s Coll., Notre Dame, IN (United States))

    1992-02-26

    Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressure than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.

  19. [Protective Effect of Schisandra Extract on Embryotoxicity and Reproductive Toxicity in Early Pregnant Rats Exposed to Benzo [a] pyrene].

    Science.gov (United States)

    Liang, Jing; Hou, Hai-yan; Sun, Yang; Chen, Ya-qiong

    2016-02-01

    To observe protective effects of Schisandra extract (SE) on embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene (Bap). Pregnant rat model was prepared using periodic screening cage method. Totally 50 female pregnant SD rats were divided into five groups by randomized block design according to the weight, i.e., the BaP model group, the low dose SE group, the middle dose SE group, the high dose SE group, the normal control group, 10 rats in each group. Rats in the BaP model group were administered with BaP at a daily dose of 2 mg/kg by gastrogavage. Rats in low, middle, and high dose SE groups were administered by gastrogavage with BaP (at a daily dose of 2 mg/kg) plus SE at a daily dose of 40, 200, and 1 000 mg/kg, respectively. Equal volume of olive oil was administered to rats in the normal control group by gastrogavage. All medication was performed for 8 successive days. Changes of rat body weight in each period were observed. The uterus embryonic total quality and ovary quality were measured, and organ index calculated. The number of corpus luteum, the number of embryo implantation, and the number of absorbed embryo were statistically calculated respectively. The implantation rate and the absorbed embryos rate were calculated. Serum levels of human chorionic gonadotrophin β (β-HCG) and progesterone (PROG) were detected by ELISA. Compared with the normal control group, the weight of 9-day pregnant rats, the number of embryo implantation, the uterus embryonic total index, ovary index, serum levels of β-HCG and PROG all decreased in the Bap model group with significant difference (P body weight, the uterus embryonic total index, and the PROG level increased in 3 dose SE groups (P pregnant rats exposed to Benzo[a]pyrene.

  20. Normal maternal behavior, but increased pup mortality, in conditional oxytocin receptor knockout females.

    Science.gov (United States)

    Macbeth, Abbe H; Stepp, Jennifer E; Lee, Heon-Jin; Young, W Scott; Caldwell, Heather K

    2010-10-01

    Oxytocin (Oxt) and the Oxt receptor (Oxtr) are implicated in the onset of maternal behavior in a variety of species. Recently, we developed two Oxtr knockout lines: a total body knockout (Oxtr-/-) and a conditional Oxtr knockout (OxtrFB/FB) in which the Oxtr is lacking only in regions of the forebrain, allowing knockout females to potentially nurse and care for their biological offspring. In the current study, we assessed maternal behavior of postpartum OxtrFB/FB females toward their own pups and maternal behavior of virgin Oxtr-/- females toward foster pups and compared knockouts of both lines to wildtype (Oxtr+/+) littermates. We found that both Oxtr-/- and OxtrFB/FB females appear to have largely normal maternal behaviors. However, with first litters, approximately 40% of the OxtrFB/FB knockout dams experienced high pup mortality, compared to fewer than 10% of the Oxtr+/+ dams. We then went on to test whether or not this phenotype occurred in subsequent litters or when the dams were exposed to an environmental disturbance. We found that regardless of the degree of external disturbance, OxtrFB/FB females lost more pups on their first and second litters compared to wildtype females. Possible reasons for higher pup mortality in OxtrFB/FB females are discussed.

  1. Pulmonary Toxicity of a Formulated Preparation of Fenvalerate in Rats Subchronically Exposed by Nose Only Inhalation for 90 Days

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective The pulmonary toxicity of a commercially available formulated preparation of Fenvalerate (Fen), a synthetic pyrethroid has been studied in rats following subchronic nose only inhalation exposure route. Method  Adult male rats were exposed to Fen for 4h/day, 5 days a week for 90 days by using Flow Past Dynamic Nose only Inhalation Chamber. Results Fen exposed rats showed a significant increase in enzymatic activities of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) which are considered as biochemical indicators of pulmonary damage. The concomitant histopathological examination of Fen exposed rats' lung revealed inflammatory changes viz., influx of mononuclear cells admixed with a few giant cells in alveolar lumen, hypetrophied bronchiolar and alveolar epithelial lining cells and presence of edematous fluid in alveolar lumen alongwith congested parenchymatous blood vessels. Conclusion These results for the first time indicate the pulmonary toxic effects of a commonly used formulated Fen preparation by using rat model and nose only inhalation as the route of exposure.

  2. On the Nature of CP Pup

    Science.gov (United States)

    Mason, E.; Orio, M.; Mukai, K.; Bianchini, A.; deMartino, D.; diMille, F.; Williams, R. E.

    2013-01-01

    We present new X-ray and optical spectra of the old nova CP Pup (nova Pup 1942) obtained with Chandra and the CTIO 4m telescope. The X-ray spectrum reveals a multi-temperature optically thin plasma reaching a maximum temperature of 36+19 keV 16 absorbed by local complex neutral material. The time resolved optical spectroscopy confirms the presence of the 1.47 hr period, with cycle-to-cycle amplitude changes, as well as of an additional long term modulation which is suggestive either of a longer pe- riod or of non-Keplerian velocities in the emission line regions. These new observational facts add further support to CP Pup as a magnetic cataclysmic variable (mCV). We compare the mCV and the non-mCV scenarios and while we cannot conclude whether CP Pup is a long period system, all observational evidences point at an intermediate polar (IP) type CV.

  3. Alaska Steller sea lion Count Database (Non-pups)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This database contains counts of adult and juvenile (non-pup) Steller sea lions on rookeries and haulouts in Alaska made between 1904 and 2015. Non-pup counts have...

  4. Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline-ethanol blends.

    Science.gov (United States)

    Bushnell, Philip J; Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Copeland, Carey B; Kleindienst, Tadeusz E; Lonneman, William A; Rogers, John M

    2015-01-01

    The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000 ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000 ppm of E0 or E85 gained more weight per gram of food consumed during the 12 days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27-29 and PND 56-63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6 months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose

  5. Weakness in the mechanical properties of the femurs of growing female rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Medical University of Bialystok, Department of Toxicology, Bialystok (Poland); Majewska, Katarzyna [University of Warmia and Mazury (Poland). Faculty of Food Science

    2005-09-01

    The study assessed the effect of cadmium (Cd) intoxication on the risk of deformities and fractures of the growing bones of female rats, in order to model human exposure to this metal. For this purpose, bone mineral density and mechanical properties of the proximal and distal ends and diaphysis of the femur were investigated in female Wistar rats exposed to 1, 5 and 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months after the onset of weaning. Daily Cd doses received from drinking water during the treatment period were in the following ranges: 0.059-0.219, 0.236-1.005 and 2.247-9.649 mg/kg body weight at 1, 5 and 50 mg Cd/l, respectively. Biomechanical properties of the femoral proximal and distal ends were evaluated in a compression test, and those of the femoral diaphysis in a cutting test, with loading perpendicular to the longitudinal axis of the bone in all tests. The mineralization and mechanical properties of the bone tissue at various locations on the femur were affected by exposure to Cd in a dose- and duration-dependent manner. Exposure to 1 mg Cd/l (corresponding to low human exposure) during skeletal development weakened the fracture strength of the femoral neck and the trabecular bone at the level of the distal end of the femur and affected the elastic properties of the cortical bone at the femoral diaphysis. At higher levels of Cd exposure, adverse effects were generally observed after a shorter exposure period than for 1 mg Cd/l, and were more advanced. The cadmium-induced weakening of the biomechanical properties of bone at particular sites on the femur correlated with the decreased bone mineralization. The results indicate that even a low exposure to Cd may affect the mineralization and biomechanical properties of growing bone, thus enhancing the risk of fracture. (orig.)

  6. Weakness in the mechanical properties of the femur of growing female rats exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Medical University of Bialystok, Department of Toxicology, Bialystok (Poland); Majewska, Katarzyna [University of Warmia and Mazury, Olsztyn (Poland). Faculty of Food Science

    2005-05-01

    This study was aimed at assessing the effect of cadmium (Cd) intoxication on the risk of deformities and fractures of the growing bone on a female rat model of human exposure to this metal. For this purpose, bone mineral density (BMD) and mechanical properties of the proximal and distal ends and diaphysis of the femur were investigated in female Wistar rats exposed to 1, 5, and 50 mg Cd L{sup -1} in drinking water for 3, 6, 9, and 12 months since weaning. Daily Cd doses received from the drinking water during the treatment period were in the ranges 0.059-0.219, 0.236-1.005, and 2.247-9.649 mg kg{sup -1} body weight at 1, 5, and 50 mg Cd L{sup -1}, respectively. Biomechanical properties of the femoral proximal and distal ends were evaluated in a compression test and those of the femoral diaphysis in a cutting test with loading perpendicular to the bone longitudinal axis in all tests. Cd dose- and exposure duration-dependently affected the mineralization and mechanical properties of the bone tissue at various locations of the femur. Exposure to 1 mg Cd L{sup -1} (corresponding to low human exposure) during skeletal development weakened the fracture strength of the femoral neck and of the trabecular bone at the level of the distal end of the femur and affected the elastic properties of the cortical bone at the femoral diaphysis. At the higher levels of Cd treatment, the adverse action generally occurred after shorter exposure than at 1 mg Cd L{sup -1} and was more seriously advanced. The Cd-induced weakening in the bone biomechanical properties at particular sites of the femur correlated with the decreased bone mineralization. The results indicate that even low exposure to Cd may affect the mineralization and biomechanical properties of growing bone, thus increasing the risk of fractures. (orig.)

  7. Formation of Hydroxymethyl DNA Adducts in Rats Orally Exposed to Stable Isotope Labeled Methanol

    Science.gov (United States)

    Lu, Kun; Gul, Husamettin; Upton, Patricia B.; Moeller, Benjamin C.; Swenberg, James A.

    2012-01-01

    Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol’s well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity. Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential. Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol. Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage. However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde. Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000 mg/kg [13CD4]-methanol by gavage for 5 days. Our data demonstrate that labeled formaldehyde arising from [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner. The results also demonstrated that the number of exogenous DNA adducts was lower than the number of endogenous hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day for 5 days, a lethal dose to humans, even after incorporating an average factor of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol into account. PMID:22157354

  8. Memory, learning, and participation of the cholinergic system in young rats exposed to environmental enrichment.

    Science.gov (United States)

    Lima, Aline P A S; Silva, Kelly; Padovan, Cláudia Maria; Almeida, Sebastião Sousa; Fukuda, Marisa Tomoe Hebihara

    2014-02-01

    The present study demonstrates the consequences of animal exposure to an enriched environment compared to animals living in a standard environment regarding learning and space memory. Male albino Wistar rats were exposed to an enriched environment for 4 weeks after the lactation period and tested in the Morris water maze in the distal and proximal clue version and in the arena. In the former test, the animals were tested at 50 days of age with 12 daily trials on two consecutive days. At the end of each session, scopolamine at the dose of 0.6 mg/kg/ml or saline solution was injected intraperitoneally. Twenty-eight days after the first phase, a new test consisting of a single trial was held (retest). An independent group of animals receiving no drug was subjected to the arena test and to the proximal clue version of the Morris maze. In the distal clue version the results did not show differences between groups in the first phase of the experiment. After 28 days (retest), the animals reared in a standard environment and treated with scopolamine exhibited a significant increase in latency compared to the group receiving the same drug and stimulated and to the group receiving saline. The arena data demonstrated a significant increase in exploratory activity in the group of animals reared in an enriched environment. The proximal clue version of the Morris maze did not show differences between groups. The results of the present study indicate that animals exposed to environmental enrichment react less to the amnesic effects of scopolamine and show an increase in exploratory activity.

  9. Reduced number of alpha- and beta-adrenergic receptors in the myocardium of rats exposed to tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Larue, D.; Kato, G.

    1981-04-09

    The concentration of alpha- and beta-adrenergic receptors--as measured by specific (/sup 3/H)WB-4101 and (-)-(/sup 3/H)dihydroalprenolol binding--was diminished by 60% below control values in the hearts of rats exposed to tobacco smoke. These changes in receptor numbers took place almost immediately after tobacco smoke exposure and were rapidly reversible after termination of the exposure. The dissociation constant, KD, for (/sup 3/H)WB-4101 was identical in exposed (KD . 0.34 +/- 0.09 nM) and control (KD . 0.35 +/- 0.07 nM) hearts but was significantly different in the case of (-)-(3H)dihydroalprenolol binding (exposed, KD . 2.83 +/- 0.30 mM vs. control KD . 5.22 +/- 0.61 nM). For beta-receptor binding there was no significant difference between exposed and control animals in the Ki values for (-)-epinephrine, (-)-norepinephrine, (-)-alprenolol, (+/-)-propranolol or timolol. (-)-Isoproterenol, however, was found to bind with lower affinity in exposed compared with control hearts. For alpha-receptor binding there was no significant difference between control and 'smoked' animals in the Ki values for (-)-epinephrine, (-0)-norepinephrine or phentolamine. The decrease in alpha- and beta-adrenergic receptor concentration may be related to the phenomenon of receptor desensitization resulting from a release of catecholamines in rats exposed to tobacco smoke.

  10. Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome exposed by oral gavage to carbon black nanoparticles

    DEFF Research Database (Denmark)

    Folkmann, Janne Kjærsgaard; Vesterdal, Lise Kristine; Sheykhzade, Majid

    2012-01-01

    Exposure to nanosized particles may increase the risk of cardiovascular diseases by endothelial dysfunction, particularly in susceptible subjects with metabolic syndrome. We investigated vasomotor dysfunction in aorta from obese and lean Zucker rats after oral exposure to nanosized carbon black (CB....... In conclusion, repeated oral exposure to CB was associated with endothelial dysfunction in rats, further aggravating the effect of metabolic syndrome.......). Rats were exposed to 1 or 10 weekly doses of 0, 0.064, 0.64 or 6.4mg/kg bodyweight and sacrificed 24h or 13 weeks later. The exposure to 10 doses of 0.064 or 0.64mg/kg reduced the acetylcholine-induced vasorelaxation in the lean and obese rats. The half maximal effect concentration values increased...

  11. Comparison of transfer and effects of Cd on rats exposed in a short experimental snail-rat food chain or to CdCl2 dosed food.

    Science.gov (United States)

    Hispard, F; de Vaufleury, A; Cosson, R P; Devaux, S; Scheifler, R; Coeurdassier, M; Gimbert, F; Martin, H; Richert, L; Berthelot, A; Badot, P-M

    2008-04-01

    Transfer and toxic effects of two cadmium (Cd) forms, inorganic (CdCl2 dosed rat food) or organic (contaminated snail-based rat food) were studied in Wistar rat. Cd concentrations in rat food were 0 and 2.5 microg Cd g(-1) for both inorganic and organic forms and a high concentration of 100 microg Cd g(-1) was also tested for the inorganic form. Rats were exposed for four weeks to contaminated food. Both forms of Cd were bioavailable to rats, with a percentage of transfer from food to rats of around 1% for all contaminated groups. Cd concentrations in rat tissues increased with increasing Cd concentrations in the food. Rats fed with organic form of Cd accumulated significantly more Cd in the main organ for Cd toxicity, the kidney, than those eating the inorganic form. Survival was not affected for any rat group but a decrease in growth and food consumption was observed for the inorganic form. As a defence system against Cd toxicity, rats increased their metallothionein (MT) synthesis at the highest Cd concentration in the target organs (kidney, liver and small intestine) and even did the same at low Cd concentrations (2.5 microg Cd g(-1)) in the kidney. At this low Cd concentration, MT induction was lower in the small intestine of rats ingesting organic Cd than those ingesting inorganic Cd. Bioavailability of organic and inorganic forms of Cd was similar, but subsequent Cd distribution within organs was different. This quantification of the trophic transfer of both inorganic and organic forms of a toxicant is a basis for a better assessment of the fate and effects of chemicals in food webs.

  12. Effect of kombucha on some trace element levels in different organs of electromagnetic field exposed rats

    Directory of Open Access Journals (Sweden)

    Ola A. Gharib

    2014-01-01

    Full Text Available Mobile phones have increased exponentially all over the world. The present study was performed to evaluate the effect of kombucha (KT on some trace element levels of brain, spleen and intestine in male albino rats exposed to a 950 MHz electromagnetic field (EMF. Four experimental groups labelled as controls, EMF group, KT group and KT + EMF group were formed with six randomly chosen animals in each group. After EMF exposure for eight weeks and the animals were sacrificed by decapitation. Brain, spleen and intestine samples were collected for trace element analysis. The group of animals subjected to electromagnetic waves caused significant increases in iron copper levels and copper/zinc ratio accompanied with a decrease of zinc level in all studied organs. Combined treatment of kombucha with EMF resulted in a successful attenuation of these adverse effects of EMF. From present findings we can state that kombucha as a supplement has an ameliorative signs against the effects of electromagnetic radiation.

  13. Factors influencing aggression toward females by male rats exposed to anabolic androgenic steroids during puberty.

    Science.gov (United States)

    Cunningham, Rebecca L; McGinnis, Marilyn Y

    2007-01-01

    Previous results showed that male rats pubertally exposed to anabolic androgenic steroids (AAS) displayed aggression towards females in response to physical provocation. This experiment examined two factors that may modulate AAS-induced behavior towards females: olfactory cues and frustration. Gonadally intact males began one of three AAS treatments at puberty (D40): testosterone propionate (T), stanozolol (S), T+S, or vehicle control. To test for the relevance of olfactory cues in the elicitation of behavior toward females, a hidden neighbor paradigm was used. The proximal stimulus was an ovariectomized (OVX) female, estrogen plus progesterone (E+P) female, or an E+P female with tape-obstructed vagina (OBS). Distal olfactory cues from a hidden neighbor were delivered from a separate cage connected to the testing arena. The vaginally obstructed, sexually receptive female (OBS) was used to determine the effects of frustration on behavior by AAS males. Both sexual and aggressive behaviors were measured. The presence of distal olfactory cues had no effect on either sexual or aggressive behavior. In the presence of E+P and OBS females, all males displayed sex behaviors, not aggression. However, AAS males displayed significantly more aggression towards proximal OVX females than controls. AAS males mounted OBS females significantly more than controls, indicating a persistence of once rewarded behavior. These results suggest (1) proximal cues of the conspecific female are more salient than distal olfactory cues in determining behavior and (2) AAS males display frustration-induced persistence in response to vaginally obstructed receptive females.

  14. Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid

    Science.gov (United States)

    Servadio, M; Melancia, F; Manduca, A; di Masi, A; Schiavi, S; Cartocci, V; Pallottini, V; Campolongo, P; Ascenzi, P; Trezza, V

    2016-01-01

    Autism spectrum disorders (ASD) are characterized by altered sociability, compromised communication and stereotyped/repetitive behaviors, for which no specific treatments are currently available. Prenatal exposure to valproic acid (VPA) is a known, although still underestimated, environmental risk factor for ASD. Altered endocannabinoid activity has been observed in autistic patients, and endocannabinoids are known to modulate behavioral traits that are typically affected in ASD. On this basis, we tested the hypothesis that changes in the endocannabinoid tone contribute to the altered phenotype induced by prenatal VPA exposure in rats, with focus on behavioral features that resemble the core and associated symptoms of ASD. In the course of development, VPA-exposed rats showed early deficits in social communication and discrimination, compromised sociability and social play behavior, stereotypies and increased anxiety, thus providing preclinical proof of the long-lasting deleterious effects induced by prenatal VPA exposure. At the neurochemical level, VPA-exposed rats displayed altered phosphorylation of CB1 cannabinoid receptors in different brain areas, associated with changes in anandamide metabolism from infancy to adulthood. Interestingly, enhancing anandamide signaling through inhibition of its degradation rescued the behavioral deficits displayed by VPA-exposed rats at infancy, adolescence and adulthood. This study therefore shows that abnormalities in anandamide activity may underlie the deleterious impact of environmental risk factors on ASD-relevant behaviors and that the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients. PMID:27676443

  15. The Effect of Citrus aurantium on Uterus Apoptosis and Serum Antioxidants in Rats Exposed to Electromagnetic Fields

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    Mansouri Elham

    2014-10-01

    Full Text Available Objective: In the industrial world, almost everyone is unavoidably exposed to ambient electromagnetic field (EMF generated from various technical and household appliances. Thus, the aim of this study was to evaluate the diminishing effects of Citrus aurantium on uterus cell injury induced by EMF. Materials and Methods: In order to examine this, 40 female Wistar rats were selected and kept for 1 week in quarantine, and then, subdivided into two groups of 20 rats and were exposed to 40 Hz of EMF (non-ionizing radiation, 0.1 tesla for 6 weeks. Group 1 received 3 cc/rat Citrus aurantium juice, and group 2 only received 3 cc Citrus aurantium. The control group only received 3 cc water using gavage method. The materials were processed and apoptosis was observed under a light microscope using TUNEL method. Results: In the experimental rats, apoptotic cells showed significant increase in the EMF groups. However, in the exposed group that received Citrus aurantium, apoptotic cells and serum malondialdehyde (MDA were decreased and superoxide dismutase (SOD was increased (P < 0.05. Conclusion: This study showed that EMF could induce cell injury on uterus tissue, and 3 cc Citrus aurantium juice has antioxidative effects on uterus tissue by reduction of apoptosis.

  16. Effects of Chronic Administration of Melatonin on Spatial Learning Ability and Long-term Potentiation in Lead-exposed and Control Rats

    Institute of Scientific and Technical Information of China (English)

    XIU-JING CAO; MING WANG; WEI-HENG CHEN; DA-MIAO ZHU; JIA-QI SHE; DI-YUN RUAN

    2009-01-01

    Objective To explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months. Methods Experiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric garage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo. Results Low dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead. Conclusion Melatonin is not suitable for normal and lead-exposed children.

  17. Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.

    Science.gov (United States)

    Shen, Ying-Ling; Chen, Shao-Tsu; Chan, Tzu-Yi; Hung, Tsai-Wei; Tao, Pao-Luh; Liao, Ruey-Ming; Chan, Ming-Huan; Chen, Hwei-Hsien

    2016-02-01

    Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use.

  18. 1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence.

    Science.gov (United States)

    Adriani, W; Canese, R; Podo, F; Laviola, G

    2007-01-01

    Administration of methylphenidate (MPH, Ritalin) to children affected by attention deficit hyperactivity disorder (ADHD) is an elective therapy, which however raises concerns for public health, due to possible persistent neuro-behavioral alterations. We investigated potential long-term consequences at adulthood of MPH exposure during adolescence, by means of behavioral and brain MRS assessment in drug-free state. Wistar adolescent rats (30- to 44-day-old) were treated with MPH (0 or 2 mg/kg once/day for 14 days) and then left undisturbed until adulthood. Levels of impulsive behavior were assessed in the intolerance-to-delay task: Food-restricted rats were tested in operant chambers with two nose-poking holes, delivering one food pellet immediately, or five pellets after a delay whose length was increased over days. MPH-exposed animals showed a less marked shifting profile from the large/late to the small/soon reward, suggesting reduced basal levels of impulsivity, compared to controls. In vivo MRI-guided 1H MRS examinations at 4.7 T in anaesthetised animals revealed long-term biochemical changes in the dorsal striatum (STR), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of MPH-exposed rats. Notably, total creatine and taurine, metabolites respectively involved in bioenergetics and synaptic efficiency, were up-regulated in the STR and conversely down-regulated in the NAcc of MPH-exposed rats. A strong correlation was evident between non-phosphorylated creatine in the STR and behavioral impulsivity. Moreover, unaltered total creatine and increased phospho-creatine/creatine ratio were detected in the PFC, suggesting improved cortical energetic performance. Because of this enduring rearrangement in the forebrain function, MPH-exposed animals may be more efficient when faced with delay of reinforcement. In summary, MPH exposure during adolescence produced enduring MRS-detectable biochemical modifications in brain reward-related circuits, which may account for

  19. Altered feeding patterns in rats exposed to a palatable cafeteria diet: increased snacking and its implications for development of obesity.

    Directory of Open Access Journals (Sweden)

    Sarah I Martire

    Full Text Available BACKGROUND: Rats prefer energy-rich foods over chow and eat them to excess. The pattern of eating elicited by this diet is unknown. We used the behavioral satiety sequence to classify an eating bout as a meal or snack and compared the eating patterns of rats fed an energy rich cafeteria diet or chow. METHODS: Eight week old male Sprague Dawley rats were exposed to lab chow or an energy-rich cafeteria diet (plus chow for 16 weeks. After 5, 10 and 15 weeks, home-cage overnight feeding behavior was recorded. Eating followed by grooming then resting or sleeping was classified as a meal; whereas eating not followed by the full sequence was classified as a snack. Numbers of meals and snacks, their duration, and waiting times between feeding bouts were compared between the two conditions. RESULTS: Cafeteria-fed rats ate more protein, fat and carbohydrate, consistently ingesting double the energy of chow-fed rats, and were significantly heavier by week 4. Cafeteria-fed rats tended to take multiple snacks between meals and ate fewer meals than chow-fed rats. They also ate more snacks at 5 weeks, were less effective at compensating for snacking by reducing meals, and the number of snacks in the majority of the cafeteria-fed rats was positively related to terminal body weights. CONCLUSIONS: Exposure to a palatable diet had long-term effects on feeding patterns. Rats became overweight because they initially ate more frequently and ultimately ate more of foods with higher energy density. The early increased snacking in young cafeteria-fed rats may represent the establishment of eating habits that promote weight gain.

  20. Altered feeding patterns in rats exposed to a palatable cafeteria diet: increased snacking and its implications for development of obesity.

    Science.gov (United States)

    Martire, Sarah I; Holmes, Nathan; Westbrook, R Fred; Morris, Margaret J

    2013-01-01

    Rats prefer energy-rich foods over chow and eat them to excess. The pattern of eating elicited by this diet is unknown. We used the behavioral satiety sequence to classify an eating bout as a meal or snack and compared the eating patterns of rats fed an energy rich cafeteria diet or chow. Eight week old male Sprague Dawley rats were exposed to lab chow or an energy-rich cafeteria diet (plus chow) for 16 weeks. After 5, 10 and 15 weeks, home-cage overnight feeding behavior was recorded. Eating followed by grooming then resting or sleeping was classified as a meal; whereas eating not followed by the full sequence was classified as a snack. Numbers of meals and snacks, their duration, and waiting times between feeding bouts were compared between the two conditions. Cafeteria-fed rats ate more protein, fat and carbohydrate, consistently ingesting double the energy of chow-fed rats, and were significantly heavier by week 4. Cafeteria-fed rats tended to take multiple snacks between meals and ate fewer meals than chow-fed rats. They also ate more snacks at 5 weeks, were less effective at compensating for snacking by reducing meals, and the number of snacks in the majority of the cafeteria-fed rats was positively related to terminal body weights. Exposure to a palatable diet had long-term effects on feeding patterns. Rats became overweight because they initially ate more frequently and ultimately ate more of foods with higher energy density. The early increased snacking in young cafeteria-fed rats may represent the establishment of eating habits that promote weight gain.

  1. Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress

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    Mohd Fahami Nur Azlina

    2012-05-01

    Full Text Available Abstract Background This study examined the effects of Palm vitamin E (PVE and α-tocopherol (α-TF supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO + XD activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS. Methods Sixty male Sprague–Dawley rats (200-250 g were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO + XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and α-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and α-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or α-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.

  2. Effects of Rambutan Peel Extract to The Number of Erythrocytes and Haemoglobin in Rats Exposed to Cigarette Smoke

    Science.gov (United States)

    Lisdiana; Dewi, F. K.

    2017-04-01

    Cigarette smoke is one of the exogenous free radicals sources. When it is inhaled, its activity may damage the structure of erythrocyte membrane function. The impacts of free radicals can be reduced through the provision of antioxidants. Rambutan fruit peel contains the phenolic compound in the form of polyphenols that are antioxidants. The purpose of this study is to determine the effect of rambutan fruit peel extracts to the number of erythrocytes and haemoglobin in rats exposed to cigarette smoke. This design used Post Test Control Group Design. A sample of 25 rats was divided into five groups, each group consisting of 5 rats. The positive control group (K+) were given a standard food and drinking water. The negative control group (K) by three cigarettes, the treatment group (KP1, KP2, KP3) by three cigarettes and skin extract of rambutan each treatment group with a dose 15 mg/kg, 30 mg/kg and 45 mg/kg for 30 days. Data on the number of erythrocytes and haemoglobin in rat blood was analysed with LSD and to determine the optimum dosage was analysed by using regression test. Research results shown that the content of rambutan fruit peel extract may increase the number of erythrocytes and haemoglobin of blood. Conclusions from this research are the rambutan fruit peel extract at a dose of 45 mg/kg body weight can increase and maintain the number of erythrocytes and haemoglobin in the blood of rat exposed to cigarette smoke.

  3. Effect of Amygdalin on the Proliferation of Hyperoxia-exposed Type Ⅱ Alveolar Epithelial Cells Isolated from Premature Rat

    Institute of Scientific and Technical Information of China (English)

    祝华平; 常立文; 李文斌; 刘汉楚

    2004-01-01

    Summary: The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in AEC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 μmol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 μmol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 μmol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.

  4. Effect of amygdalin on the proliferation of hyperoxia-exposed type II alveolar epithelial cells isolated from premature rat.

    Science.gov (United States)

    Zhu, Huaping; Chang, Liwen; Li, Wenbin; Liu, Hanchu

    2004-01-01

    The pathogenesis of hyperoxia lung injury and the mechanism of amygdalin on type 2 alveolar epithelial cells (AEC2) isolated from premature rat lungs in vitro were investigated. AEC2 were obtained by primary culture from 20-days fetal rat lung and hyperoxia-exposed cell model was established. Cell proliferating viability was examined by MTT assay after treatment of amygdalin at various concentrations. DNA content and the proliferating cell nuclear antigen (PCNA) protein expression of AEC2 were measured by using flow cytometry and immunocytochemistry respectively after 24 h of hyperoxia exposure or amygdalin treatment. The results showed that hyperoxia inhibited the proliferation and decreased PCNA protein expression in A-EC2 of premature rat in vitro. Amygdalin at the concentration range of 50-200 micromol/L stimulated the proliferation of AEC2 in a dose-dependent manner, however, 400 micromol/L amygdalin inhibited the proliferation of AEC2. Amygdalin at the concentration of 200 micromol/L played its best role in facilitating proliferation of AEC2s in vitro and could partially ameliorated the changes of proliferation in hyperoxia exposed AEC2 of premature rat. It has been suggested that hyperoxia inhibited the proliferation of AEC2s of premature rat, which may contribute to hyperoxia lung injury. Amygdalin may play partial protective role in hyperoxia-induced lung injury.

  5. Antioxidant effects of Dendropanax morbifera Léveille extract in the hippocampus of mercury-exposed rats

    OpenAIRE

    2015-01-01

    Background Dendropanax morbifera Léveille has been employed for the treatment of infectious diseases using folk medicine. In this study, we evaluated the antioxidant effects of a leaf extract of Dendropanax morbifera Léveille in the hippocampus of mercury-exposed rats. Methods Seven-week-old Sprague–Dawley rats received a daily intraperitoneal injection of 5 μg/kg dimethylmercury and/or oral Dendropanax morbifera Léveille leaf extract (100 mg/kg) for 4 weeks. Animals were sacrificed 2 h after...

  6. A STUDY OF FISCHER 344 RATS EXPOSED TO SILICA DUST FOR SIX MONTHS AT CONCENTRATIONS OF 0, 2, 10 OR 20 MG / M3.

    Energy Technology Data Exchange (ETDEWEB)

    KUTZMAN,R.S.

    1984-02-01

    The major objective of this study was to relate the results of a series of functional tests to the compositional and structural alterations in the rat lung induced by subchronic exposure to silica dust. Fischer-344 rats were exposed for 6 hours/day, 5 days/week for 6 months to either 0, 2, 10, or 20 mg SiO{sub 2}/m{sup 3}. The general appearance of the exposed rats was not different from that of the controls. Interestingly, female rats exposed to silica dust, at all tested concentrations, gained more weight than the controls. The lung weight and the lung-to-body weight ratio was greater in the male rats exposed to the highest concentration of silica dust.

  7. Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures

    Science.gov (United States)

    Miller, Anna P.; Shah, Alok S.; Aperi, Brandy V.; Kurpad, Shekar N.; Stemper, Brian D.; Glavaski-Joksimovic, Aleksandra

    2017-01-01

    Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h

  8. Ethylene oxide in blood of ethylene-exposed B6C3F1 mice, Fischer 344 rats, and humans.

    Science.gov (United States)

    Filser, Johannes Georg; Kessler, Winfried; Artati, Anna; Erbach, Eva; Faller, Thomas; Kreuzer, Paul Erich; Li, Qiang; Lichtmannegger, Josef; Numtip, Wanwiwa; Klein, Dominik; Pütz, Christian; Semder, Brigitte; Csanády, György András

    2013-12-01

    The gaseous olefin ethylene (ET) is metabolized in mammals to the carcinogenic epoxide ethylene oxide (EO). Although ET is the largest volume organic chemical worldwide, the EO burden in ET-exposed humans is still uncertain, and only limited data are available on the EO burden in ET-exposed rodents. Therefore, EO was quantified in blood of mice, rats, or 4 volunteers that were exposed once to constant atmospheric ET concentrations of between 1 and 10 000 ppm (rodents) or 5 and 50 ppm (humans). Both the compounds were determined by gas chromatography. At ET concentrations of between 1 and 10 000 ppm, areas under the concentration-time curves of EO in blood (µmol × h/l) ranged from 0.039 to 3.62 in mice and from 0.086 to 11.6 in rats. At ET concentrations ≤ 30 ppm, EO concentrations in blood were 8.7-fold higher in rats and 3.9-fold higher in mice than that in the volunteer with the highest EO burdens. Based on measured EO concentrations, levels of EO adducts to hemoglobin and lymphocyte DNA were calculated for diverse ET concentrations and compared with published adduct levels. For given ET exposure concentrations, there were good agreements between calculated and measured levels of adducts to hemoglobin in rats and humans and to DNA in rats and mice. Reported hemoglobin adduct levels in mice were higher than calculated ones. Furthermore, information is given on species-specific background adduct levels. In summary, the study provides most relevant data for an improved assessment of the human health risk from exposure to ET.

  9. Haematological, Biochemical and Antioxidant Changes in Wistar Rats Exposed to Dichlorvos Based Insecticide Formulation Used in Southeast Nigeria

    Directory of Open Access Journals (Sweden)

    Kingsley C. Kanu

    2016-11-01

    Full Text Available The indiscriminate use of pesticide is a treat to non-target organisms. This study evaluates the haematological and biochemical changes induced by inhalation of local Nigerian dichlorvos insecticide on rats. The rats were randomly assigned to a control group which received only food and water and a test group which, in addition to food and water, was exposed to the pesticide for a period of 4 h daily for 28 days, after which exposure was discontinued for seven days. Five animals were sacrificed from each group on days 1, 7, 14, 21, 28 and 35, and blood was collected by cardiac puncture for haematological, biochemical and antioxidant analysis. Results obtained showed lowered values of red blood cell count (RBC, packed cell volume (PCV, haemoglobin, mean cell haemoglobin (MCH and mean cell haemoglobin concentration (MCHC (p < 0.05 with increased white blood cell count (WBC and platelet counts after day 14 when compared to the control group. Liver enzymes aspartate amino transaminase (AST and alanine amino transaminase (ALT were higher in the exposed rats compared to the control group (p < 0.05. Urea and creatinine concentrations increased significantly after day 1 and at day 28, while superoxide dismutase (SOD, gluthathione (GSH and catalase (CAT activity increased significantly compared to the control after day 1, day 14 and day 21, respectively. The RBC, PCV and haemoglobin values of all exposed rats were restored to normal following withdrawal of the pesticide, though AST, ALT, urea, creatinine and, glutathione values remained significantly high compared to the control. Inhalation of the local insecticide is toxic to the blood, liver and kidney of laboratory rats and may be deleterious to human health following long-term exposure.

  10. Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

    Directory of Open Access Journals (Sweden)

    Fedor Simko

    2014-01-01

    Full Text Available Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day or melatonin (10 mg/kg/day. Exposure to continuous light led to hypertension, left ventricular (LV hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

  11. Effect of ascorbic acid on fatigue of skeletal muscle fibres in long-term cold exposed Sprague Dawley rats.

    Science.gov (United States)

    Rashid, Aneeqa; Khan, Umar Ali; Ayub, Muhammad

    2011-01-01

    On exposure to prolonged cold temperature, the body responds for effective heat production both by shivering and non-shivering thermogenesis. Cold exposure increases the production of reactive oxygen species which influence the sarcoplasmic reticulum Ca++ release from the skeletal muscles and affect their contractile properties. The role of ascorbic acid supplementation on force of contraction during fatigue of cold exposed skeletal muscles was evaluated in this study. Ninety healthy, male Sprague Dawley rats were randomly divided into three groups of control (I), cold exposed (II), and cold exposed with ascorbic acid 500 mg/L supplementation mixed in drinking water (III). Group II and III were given cold exposure by keeping their cages in ice-filled tubs for 1 hr/day for one month. After one month, the extensor digitorum longus muscle was dissected out and force of contraction during fatigue in the skeletal muscle fibres was analysed on a computerised data acquisition system. The cold exposed group showed a significant delay in the force of contraction during fatigue of skeletal muscle fibres compared to control group. Group III showed easy fatigability and a better force of contraction than the cold exposed group. Ascorbic acid increases the force of contraction and decreases resistance to fatigue in the muscles exposed to chronic cold.

  12. Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload.

    Science.gov (United States)

    Maaroufi, Karima; Had-Aissouni, Laurence; Melon, Christophe; Sakly, Mohsen; Abdelmelek, Hafedh; Poucet, Bruno; Save, Etienne

    2014-01-01

    The increasing use of mobile phone technology over the last decade raises concerns about the impact of high frequency electromagnetic fields (EMF) on health. More recently, a link between EMF, iron overload in the brain and neurodegenerative disorders including Parkinson's and Alzheimer's diseases has been suggested. Co-exposure to EMF and brain iron overload may have a greater impact on brain tissues and cognitive processes than each treatment by itself. To examine this hypothesis, Long-Evans rats submitted to 900 MHz exposure or combined 900 MHz EMF and iron overload treatments were tested in various spatial learning tasks (navigation task in the Morris water maze, working memory task in the radial-arm maze, and object exploration task involving spatial and non spatial processing). Biogenic monoamines and metabolites (dopamine, serotonin) and oxidative stress were measured. Rats exposed to EMF were impaired in the object exploration task but not in the navigation and working memory tasks. They also showed alterations of monoamine content in several brain areas but mainly in the hippocampus. Rats that received combined treatment did not show greater behavioral and neurochemical deficits than EMF-exposed rats. None of the two treatments produced global oxidative stress. These results show that there is an impact of EMF on the brain and cognitive processes but this impact is revealed only in a task exploiting spontaneous exploratory activity. In contrast, there are no synergistic effects between EMF and a high content of iron in the brain.

  13. Beneficial effects of the sigma1 receptor agonists igmesine and dehydroepiandrosterone against learning impairments in rats prenatally exposed to cocaine.

    Science.gov (United States)

    Meunier, Johann; Maurice, Tangui

    2004-01-01

    In utero cocaine (IUC) exposure results in offspring rats in complex neurochemical and behavioral alterations, particularly affecting learning and memory processes. We examined here the impact of IUC exposure on memory functions in male and female offspring rats and report that selective sigma(1) (sigma(1)) receptor agonists are effective in reversing the deficits. Dams received a daily cocaine, 20 mg/kg ip, injection between gestational days E17 to E20. Learning was examined in offspring between day P30 and P41 using delayed alternation in the T-maze, water-maze learning and passive avoidance. Both male and female rats prenatally exposed to cocaine showed delayed alternation deficits and impairments of acquisition of a fixed platform position in the water maze, as shown by higher acquisition latencies and diminutions of time spent in the training quadrant during the probe test. The acquisition of a daily changing platform position also demonstrated impaired working memory. Finally, passive avoidance deficits were observed. Pretreatment with the synthetic sigma(1) agonist igmesine (0.1-1 mg/kg ip) or the neuroactive steroid dehydroepiandrosterone (DHEA 10-40 mg/kg ip) reversed the prenatal cocaine-induced learning deficits in offspring rats for each test. The sigma(1) antagonist BD1063 (1 mg/kg ip) failed to affect performances alone but blocked the igmesine and DHEA effects, confirming the involvement of the sigma(1) receptor. IUC exposure thus results in marked memory deficits, affecting spatial and nonspatial short- and long-term memories in juvenile male and female offspring rats. The activation of the sigma(1) neuromodulatory receptor allows a complete behavioral recovery of the memory functions in prenatally cocaine-exposed rats.

  14. Effects of chloramphenicol preconditioning on oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia

    Institute of Scientific and Technical Information of China (English)

    陈丽峰; 柳君泽; 党永明; 宋熔

    2004-01-01

    Objective: To investigate the roles of chloramphenicol (CAP) preconditioning in the oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia during acute hypoxia by observing the changes of mitochondrial oxidative respiratory function and cytochrome C oxidase (COX) activity. Methods: Adult male Wistar rats were randomly divided into 4 groups: control (C), medication (M), hypoxia (H), and medication plus hypoxia (MH). Rats in groups M and MH were administered by peritoneal injection of CAP (50 mg/kg) every 12 h for 7 d before decapitation, but those in groups H and MH were exposed to a hypobaric chamber simulating 5 000 m high altitude for 24 h. The rat cerebral cortex was removed and mitochondria were isolated by centrifugation. Mitochondrial respiratory function and COX activity were measured by Clark oxygen electrode. Results: Compared with Group C, Group H showed significantly elevated state 4respiration (ST4), decreased state 3 respiration (ST3), and respiratory control rate (RCR) in mitochondrial respiration during acute hypoxic exposure. ST3 in Group MH was significantly lower than that in Group C, but was not significantly different from that in Groups H and M, while ST4 in Group MH was significantly lower than that in groups C and H. RCR in Group MH was higher than that in Group H, but lower than that in Group C. COX activity in Group H was significantly lower than that in Group C. In Group MH, COX activity increased and was higher than that in Group H, but was still lower than that in Group C. Conclusion: Acute hypoxic exposure could lead to mitochondrial respiratory dysfunction, suggesting that CAP preconditioning might be beneficial to the recovery of rat respiratory finction. The change of COX activity is consistent with that of mitochondrial respiratory function during acute hypoxic exposure and CAP-administration, indicating that COX plays an important role in oxidative phosphorylation function of mitochondria from

  15. Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation.

    Science.gov (United States)

    Monteiro Filho, Waldo Oliveira; de Torres, Sandra Maria; Amorim, Marleyne José Afonso Accioly Lins; Andrade, Anderson Joel Martino; de Morais, Rosana Nogueira; Tenorio, Bruno Mendes; da Silva Junior, Valdemiro Amaro

    2014-10-01

    Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.

  16. Oxidative stress is reduced in Wistar rats exposed to smoke from tobacco and treated with specific broad-band pulse electromagnetic fields

    Directory of Open Access Journals (Sweden)

    Bajić V.

    2009-01-01

    Full Text Available There have been a number of attempts to reduce the oxidative radical burden of tobacco. A recently patented technology, pulse electromagnetic technology, has been shown to induce differential action of treated tobacco products versus untreated products on the production of reactive oxygen species (ROS in vivo. In a 90-day respiratory toxicity study, Wistar rats were exposed to cigarette smoke from processed and unprocessed tobacco and biomarkers of oxidative stress were compared with pathohistological analysis of rat lungs. Superoxide dismutase (SOD activity was decreased in a dose-dependent manner to 81% in rats exposed to smoke from normal cigarettes compared to rats exposed to treated smoke or the control group. These results correspond to pathohistological analysis of rat lungs, in which those rats exposed to untreated smoke developed initial signs of emphysema, while rats exposed to treated smoke showed no pathology, as in the control group. The promise of inducing an improved health status in humans exposed to smoke from treated cigarettes merits further investigation.

  17. Minute virus of canines (MVC, canine parvovirus type-1): pathogenicity for pups and seroprevalence estimate.

    Science.gov (United States)

    Carmichael, L E; Schlafer, D H; Hashimoto, A

    1994-04-01

    Minute virus of canines (MVC, canine parvovirus type-1) caused inapparent to severe illness in neonatal specific-pathogen-free pups exposed by the oronasal route. The experimental disease was generally mild. Four of 21 infected pups had clinical signs of respiratory illness, but only 2 pups, not euthanized during the early postinoculation period, developed severe illness or died. Principal pathologic changes included bronchitis and interstitial pneumonia with various degrees of lymphadenitis. In contrast to the reported field cases, enteric signs were absent in the experimentally infected animals. Histopathologic changes in the small intestine were mild or absent. Bronchial, bronchiolar, and alveolar epithelial cells appeared to be the sites of initial and most extensive viral growth, reflecting the pattern of histopathologic changes. The disease caused by MVC was mild in comparison to that caused by canine parvovirus-type 2. MVC now appears to be established as a cause of illness in young pups and of transplacental infections with embryo resorption. The prevalence of MVC hemagglutination-inhibiting antibodies was high (approximately 50%) in adult dog sera from widely separated geographic areas of the United States.

  18. Acute treatment with 5-HT3 receptor antagonist, tropisetron, reduces immobility in intact female rats exposed to the forced swim test.

    Science.gov (United States)

    Bravo, Gabriela; Maswood, Sharmin

    2006-10-01

    The effects of tropisetron, a 5-HT3 receptor antagonist, were evaluated in adult Fischer female rats exposed to the Forced Swim Test (FST). Rats selected on the days of proestrus or estrus was immersed in a cylinder of water for 2 consecutive days. Rats were exposed to the FST for 15 min on day 1 (pretest), followed by a 5-min session (test), 24 h later. The proestrous-estrous group consisted of rats that were exposed to the FST on their proestrous stage (pretest); then 24 h later the same rats were exposed to the FST on their estrous stage (test). Rats in the estrous-diestrous group were exposed to the FST on their estrous stage (pretest) and 24 h later on their diestrous stage (test). Rats were injected intraperitoneally with saline or 1.0 or 2.0 mg/kg tropisetron 30 min prior to exposure to the cylinder on the test day. Immobility, swimming, and struggling behaviors were scored for 5 min. There was a significant decline in immobility after treatment with 2.0 mg/kg tropisetron in both groups. In addition, a significant decline in swimming was observed in the estrous rats (proestrous-estrous group) after treatment with 2.0 mg/kg tropisetron. There were no significant effects of tropisetron on struggling in any groups examined.

  19. Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

    Science.gov (United States)

    Supriya, Ch.; Reddy, P. Sreenivasula

    2015-06-01

    Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility

  20. [Immunological reactivity of rats exposed on the Kosmos-605 and 690 biosatellites].

    Science.gov (United States)

    Ivanov, A A; Shvets, V N

    1979-01-01

    Immunological reactivity of rats flown aboard the biosatellites Cosmos-605 and Cosmos-690 was compared with respect to the complementary activity of serum and frequency antibodies to sheep red blood cells. Cosmos-605 rats showed changes that rapidly returned to the normal whereas Cosmos-690 rats irradiated inflight with a dose of 800 rad exhibited significant and stable changes in immunological reactivity. Those latter seemed to be associated with the combined effect of ionizing radiation and other space flight factors.

  1. Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

    Science.gov (United States)

    Lindquist, Derick H

    2013-04-01

    Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure.

  2. DEVELOPMENT OF A NOVEL METHOD FOR ANALYSIS OF TRANSCRIPTIONAL CHANGES IN TRANSITIONAL EPITHELIUM FROM URINARY BLADDERS OF RATS EXPOSED TO DRINKING WATER DISINFECTION BY-PRODUCTS

    Science.gov (United States)

    Development of a Novel Method for Analysis of Transcriptional Changes in Transitional Epithelium from Urinary Bladders of Rats Exposed to Drinking Water Disinfection By- products.Epidemiologic studies in human populations that drink chemically disinfected drinking wa...

  3. Identification of Coordinately Regulated Functional Modules in Thyroid Tissues from Rats Exposed to a Tumorigenic and a Non-Tumorigenic Conazole Fungicide Using Oncomine®

    Science.gov (United States)

    Conazoles are triazole- or imidazole-containing fungicides used in agriculture and medicine. Using transcriptomic analysis of rat thyroid tissues exposed to either tumorigenic or non-tumorigenic structurally related conazoles, we identified new findings on thyroid gene expressio...

  4. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    Data.gov (United States)

    U.S. Environmental Protection Agency — pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets. This dataset...

  5. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

  6. Rats offspring exposed to Ipomoea Carnea and handling during gestation: neurochemical evaluation

    Directory of Open Access Journals (Sweden)

    Aline Schwarz

    2007-05-01

    Full Text Available The present study evaluated the central monoamine levels of male and female adult rat offspring exposed orally by gavage to 0.0, 0.7, 3.0 and 15.0 mg/kg I. carnea aqueous extract daily, from gestation day (GD 5 to GD 21. Several alterations in the monoamine activity systems were observed. However, the major differences were noted between the 0.0 mg/kg and the no gavage control groups, showing that alterations showing that alterations were not due to the alterations to the aqueous extract. The control data showed that gavage and handling of dams were stressful enough to produce a significant decline in 3,4-dihydroxyphenylacetic acid (DOPAC and an increase in vanilmandelic acid (VMA, indicating decreased dopamine (DA and enhanced norepinephrine (NE activity, respectively.Estudo anterior realizado em filhotes de ratas tratadas diariamente por gavage com 0,0, 0,7, 3,0 e 15,0 mg/kg de uma solução aquosa obtida de folhas frescas da Ipomoea carnea, do dia 5 ao dia 21 da gestação, mostrou poucas alterações comportamentais na prole em vida adulta. O presente estudo teve como objetivo avaliar a atividade e níveis das monoaminas cerebrais nas proles masculina e feminina expostas ao mesmo tratamento acima descrito. As maiores alterações encontradas, entretanto, foram entre os grupos 0,0 mg/kg e controle negativo (no gavage, impedindo a atribuição das alterações encontradas à solução aquosa. O dados resultantes do grupo controle sugerem que o estresse provocado pela gavage e pelo manuseio das fêmeas enquanto prenhes é suficiente para produzir um importante declínio nos níveis do ácido 3,4 dihidroxifenilacético (DOPAC e um não menos importante aumento nos níveis do ácido vanilmandélico (VMA, promovendo maior atividade do sistema noradrenérgico (NE.

  7. Influência da desnutrição promovida pela dieta básica regional sobre o perfil de ácidos graxos do leite materno, o crescimento e o desenvolvimento de ratos jovens Malnutrition promoted by a basic regional diet alters the fatty acid profile of breast milk, and the growth and development of rat pups

    Directory of Open Access Journals (Sweden)

    Amanda Santos de Souza

    2009-08-01

    apresentaram valores de massa corporal estatisticamente semelhantes aos do grupo controle, o que não foi observado nos filhotes machos do grupo recuperado. CONCLUSÃO: O comprometimento da massa corporal materna durante a lactação e o déficit na taxa de crescimento dos filhotes, machos e fêmeas, se deveram à ingestão da Dieta Básica Regional multideficiente. A diminuição dos teores de ácidos graxos específicos do leite materno poderia, ainda que não completamente, justificar o déficit de crescimento observado.OBJECTIVE: The aim of this study was to assess the effects of a basic regional diet and nutritional rehabilitation during the critical growth and development periods of rat pups and their effects on body weight and tissue mass gain; to assess food intakes of dams during gestation and lactation and of male and female pups until they were 70 days old; and to assess the percentages of fatty acids in experimental diets and breast milk. METHODS: Male and female Wistar rats were used. After mating, pregnant rats were divided into three groups: 1 Control group, consisting of dams from the beginning of pregnancy (21 days and pups from birth until they were 70 days old (totaling 91 days fed commercial lab chow; 2 Malnourished group, consisting of dams and pups fed the regional basic diet chow for the same 91 days; and 3 rehabilitated group, consisting of dams fed the regional basic diet during pregnancy and lactation and pups fed commercial lab chow after weaning (at 21 days until they were 70 days old. The animals received food and water ad libitum and were maintained in a room with controlled temperature and lighting conditions. The animals were monitored daily to record body weight and food intake. At 70 days, the offspring were killed by decapitation and the brain, heart, kidneys and liver were removed and weighed. The results were analyzed using the Student's t-test, analysis of variance and Bonferroni post hoc test. RESULTS: Important changes were observed in

  8. Oxidative stress in testicular tissues of rats exposed to cigarette smoke and protective effects of caffeic acid phenethyl ester

    Institute of Scientific and Technical Information of China (English)

    Hüseyin Ozyurt; Hidir Pekmez; Bekir Suha Parlaktas; Ilter Kus; Birsen Ozyurt; Mustafa Sarsllmaz

    2006-01-01

    Aim: To show the oxidative stress after cigarette smoke exposure in rat testis and to evaluate the effects of caffeic acid phenethyl ester (CAPE). Methods: Twenty-one rats were divided into three groups of seven. Animals in Group Ⅰwere used as control. Rats in Group Ⅱ were exposed to cigarette smoke only (4 x 30 min/d) and rats in Group Ⅲall the rats were killed and the levels of nitric oxide (NO) and anti-oxidant enzymes such as superoxide-dismutase,catalase and glutathione peroxidase (GSH-Px) and the level of malondialdehyde were studied in the testicular tissues of rats with spectrophotometric analysis. Results: There was a significant increase in catalase and superoxide-dismutase activities in Group Ⅱ when compared to the controls, but the levels of both decreased after CAPE administration in Group Ⅲ. GSH-Px activity was decreased in Group Ⅱ but CAPE caused an elevation in GSH-Px activity in Group Ⅲ.The difference between the levels of GSH-Px in Group Ⅰ and Group Ⅱ was significant, but the difference between groups Ⅱ and Ⅲ was not significant. Elevation of malondialdehyde after smoke exposure was significant and CAPE caused a decrease to a level which was not statistically different to the control group. A significantly increased level of NO after exposure to smoke was reversed by CAPE administration and the difference between NO levels in groups Ⅰ and Ⅲ was statistically insignificant. Conclusion: Exposure to cigarette smoke causes changes in the oxidative enzyme levels in rat testis, but CAPE can reverse these harmful effects.

  9. A Survey of the Relationship Between Noised Pollution, Honey and Vitamin E and Plasma Level of Blood Sexual Hormones in Noise-Exposed Rats

    Directory of Open Access Journals (Sweden)

    Kenani

    2015-02-01

    Full Text Available Background This study was conducted to examine the efficacy of honey and vitamin E on fertilization capacity of noise-exposed rats by assessing whether the plasma sexual hormones levels i.e. follicle stimulating hormone (FSH, luteinizing hormone (LH and testosterone are altered in relation with noise stress. Objectives Therefore, this study aimed to evaluate the effects of honey and vitamin E on the levels of sex hormones and male fertilization capacity of noise-exposed rats. Materials and Methods This study targeted 24 male rats that were randomly divided into four equal groups including the control group that were not exposed to noise and experimental groups 1, 2 and 3 that were the untreated, honey treated and vitamin E treated groups, respectively; all of which were exposed to noise for 50 days. Next, in order to measure serum sexual hormones, blood samples of experimental and control groups were taken and analyzed. Also in order to investigate the fertility capacity of rats, the male rats of all groups were coupled with female rats. Results The results showed that in the male rats exposed to the noise stress, the levels of FSH and LH rose and the testosterone secretion fell sharply compared to not exposed rats. Additionally, the continuing effects of noise stress injury could reduce the weight of the fetus and the number of live fetuses and survival rate of the fetus. However, honey and vitamin E improved serum testosterone concentration, while declined plasma FSH and LH secretion in noise-exposed rats and enhanced fertility rate by increasing the rate of healthy alive fetuses. Conclusions It seems that noise pollution has harmful effects on the fertility of males. Also these findings may suggest the use of a natural curative approach rather than pharmaceutical drugs to optimize both neuroendocrine gonadal axis and testicular integrity induced by pathogenesis stress, and enhance fertility capacity in men.

  10. The effects of microwave emitted by cellular phones on ovarian follicles in rats.

    Science.gov (United States)

    Gul, Abdulaziz; Celebi, Hacer; Uğraş, Serdar

    2009-11-01

    The aim of this study was to investigate whether there were any toxic effects of microwaves of cellular phones on ovaries in rats. In this study, 82 female pups of rats, aged 21 days (43 in the study group and 39 in the control group) were used. Pregnant rats in the study group were exposed to mobile phones that were placed beneath the polypropylene cages during the whole period of pregnancy. The cage was free from all kinds of materials, which could affect electromagnetic fields. A mobile phone in a standby position for 11 h and 45 min was turned on to speech position for 15 min every 12 h and the battery was charged continuously. On the 21st day after the delivery, the female rat pups were killed and the right ovaries were removed. The volumes of the ovaries were measured and the number of follicles in every tenth section was counted. The analysis revealed that in the study group, the number of follicles was lower than that in the control group. The decreased number of follicles in pups exposed to mobile phone microwaves suggest that intrauterine exposure has toxic effects on ovaries. We suggest that the microwaves of mobile phones might decrease the number of follicles in rats by several known and, no doubt, countless unknown mechanisms.

  11. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  12. Long-term health effects in hamsters and rats exposed chronically to man-made vitreous fibers

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.M.; Ortiz, L.W.; Archuleta, R.F.; Johnson, N.F.

    1986-01-01

    Rats and hamsters were exposed to several types of airborne man-made vitreous fibers. Exposure protocols were ''nose-only'' 6 h a day, 5 d a week for 24 m with surviving animals maintained for the rest of their lives. Challenge aerosols consisted of 4 types of fibrous glass, 1 refractory ceramic fiber (RCF), and 1 mineral wool fiber. UICC crocidolite asbestos and clean air served as positive and negative controls for the inhalation groups. Groups of additional controls were unmanipulated caged animals, intraperitoneally (IP) injected animals, and intratracheally (IT) instilled animals. Animals, after their deaths, were examined macroscopically and microscopically. Fiber lung burdens were significant for the inhalation exposures and related to the mean diameters of the fibrous challenge aerosols. The inhalation exposures with MMVF did not result in any adverse effects except for a mesothelioma of the lung in 1 hamster exposed to the RCF, not a statistically significant finding. Consistent with other reported work, abdominal mesotheliomas were induced in the groups of hamsters and rats injected IP with 0.45-micron mean diameter fibrous glass, RCF, and crocidolite asbestos. With IT instillations, primary lung tumors were found only in hamsters and rats receiving UICC crocidolite; no lung tumors occurred in animals instilled IT with 2 types of MMVF. 28 refs., 2 figs., 18 tabs.

  13. Effects of niacin on nitric oxide synthase expression in rat lungs exposed to silica

    Institute of Scientific and Technical Information of China (English)

    WANG Shixin; DU Haike; ZHANG Xizhen; CAI Shaoxi; FAN Huaquan; WANG Chang'en

    2004-01-01

    The aim of this study was to evaluate the effects of niacin in diet on the expression of nitric oxide synthase (NOS) in rat lungs of the animal model of silicosis established by direct tracheal instillation of silica particles into rat lungs surgically. The niacin concentration in serum was analyzed by high performance liquid chromatography (HPLC). The expression of inducible nitric oxide synthase (iNOS) protein in paraffin-embedded lung sections was determined by streptavidin/peroxidase (SP) staining. Quantitative analysis by Image-Pro Plus was also performed on the expression of iNOS. The results showed that niacin concentration in serum of the niacin-treated rats was significantly higher than that in the control and silica-treated rats. After 7 days of silica instillation, iNOS integrated optical density (IOD) in rat lungs and total NOS and iNOS activities in bronchoalveolar lavage fluid (BALF) in silica-treated rats rose by 273420.75, 2.61 units/mL and 1.89 units/mL respectively, when compared with those in the control rats. Niacin treatment significantly reduced silica-induced iNOS IOD in rat lung tissues and total NOS and iNOS activities in BALF supernatant by 248292.35, 1.50 units/mL and 0.91 units/mL, respectively, as compared with those in silica-treated rats. Therefore, niacin can effectively attenuate the pathological expression of NOS in rat lung tissues induced by silica particles.

  14. [Morphological study of the adrenals of rats exposed on the Kosmos-690 satellite].

    Science.gov (United States)

    Savina, E A; Alekseev, E I

    1979-01-01

    Adrenals of 12 rats flown aboard the biosatellite Cosmos-690 and 30 rats used in the ground-based experiments Control-1 and Control-2 were studied morphologically. The animals were sacrificed on the 2nd and 27th days after completion of the experiments (i. e., on the 12 and 37th days after irradiation at a total dose of 800 rad). A comparative study of morphological changes in the adrenals of flight and control rats did not show any distinct differences. It is therefore concluded that space flight factors did not produce a significant effect on the adrenal response to irradiation at a dose of 800 rad.

  15. The hepatic Igf2/H19 locus is not altered in 1-day old pups born to obese-prone Sprague-Dawley rats fed a low protein diet containing adequate folic acid

    Science.gov (United States)

    Gong et al. (Epigenetics, 2010) found, using diets low in folic acid, that compared to an 18% protein diet a 9% protein diet fed to pregnant Sprague-Dawley rats resulted in increased Igf2 and H19 gene expression in the liver of day 0 male offspring. In addition DNA methylation in the Imprinting Cont...

  16. Quantification of epithelial cell differentiation in mammary glands and carcinomas from DMBA- and MNU-exposed rats.

    Directory of Open Access Journals (Sweden)

    Deepak Sharma

    Full Text Available Rat mammary carcinogenesis models have been used extensively to study breast cancer initiation, progression, prevention, and intervention. Nevertheless, quantitative molecular data on epithelial cell differentiation in mammary glands of untreated and carcinogen-exposed rats is limited. Here, we describe the characterization of rat mammary epithelial cells (RMECs by multicolor flow cytometry using antibodies against cell surface proteins CD24, CD29, CD31, CD45, CD49f, CD61, Peanut Lectin, and Thy-1, intracellular proteins CK14, CK19, and FAK, along with phalloidin and Hoechst staining. We identified the luminal and basal/myoepithelial populations and actively dividing RMECs. In inbred rats susceptible to mammary carcinoma development, we quantified the changes in differentiation of the RMEC populations at 1, 2, and 4 weeks after exposure to mammary carcinogens DMBA and MNU. DMBA exposure did not alter the percentage of basal or luminal cells, but upregulated CD49f (Integrin α6 expression and increased cell cycle activity. MNU exposure resulted in a temporary disruption of the luminal/basal ratio and no CD49f upregulation. When comparing DMBA- or MNU-induced mammary carcinomas, the RMEC differentiation profiles are indistinguishable. The carcinomas compared with mammary glands from untreated rats, showed upregulation of CD29 (Integrin β1 and CD49f expression, increased FAK (focal adhesion kinase activation especially in the CD29hi population, and decreased CD61 (Integrin β3 expression. This study provides quantitative insight into the protein expression phenotypes underlying RMEC differentiation. The results highlight distinct RMEC differentiation etiologies of DMBA and MNU exposure, while the resulting carcinomas have similar RMEC differentiation profiles. The methodology and data will enhance rat mammary carcinogenesis models in the study of the role of epithelial cell differentiation in breast cancer.

  17. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

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    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  18. MicroRNA Profiling in the Medial and Lateral Habenula of Rats Exposed to the Learned Helplessness Paradigm

    DEFF Research Database (Denmark)

    Svenningsen, Katrine; Venø, Morten T; Henningsen, Kim

    2016-01-01

    Depression is a highly heterogeneous disorder presumably caused by a combination of several factors ultimately causing the pathological condition. The genetic liability model of depression is likely to be of polygenic heterogeneity. miRNAs can regulate multiple genes simultaneously and therefore...... are candidates that align with this model. The habenula has been linked to depression in both clinical and animal studies, shifting interest towards this region as a neural substrate in depression. The goal of the present study was to search for alterations in miRNA expression levels in the medial and lateral...... habenula of rats exposed to the learned helplessness (LH) rat model of depression. Ten miRNAs showed significant alterations associating with their response to the LH paradigm. Of these, six and four miRNAs were significantly regulated in the MHb and LHb, respectively. In the MHb we identified miR-490, mi...

  19. Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field.

    Science.gov (United States)

    Aydin, M; Cevik, A; Kandemir, F M; Yuksel, M; Apaydin, A M

    2009-04-01

    This study investigates the effects of the electromagnetic field (EMF) resulting from the 170 kV high-voltage power lines on hormonal status, on progesterone and 17-beta estradiol levels, and on morphology of the uterus and ovaries associated with biochemical parameters of adult Wistar female rats. The rats were assigned to experimental (21) and control groups (7). The rats in the experimental group were housed in a wooden barn with 7.5 m vertical distance to the power line. Groups 1, 2, and 3 were exposed continuously (24 h) to electric-electromagnetic fields (ELF-EMFs) (48.21 +/- 1.58 mG) for 1, 2, and 3 months, respectively. The rats of group 4 served as the control and were placed in laboratory conditions (The average value of the ELF was 0.75 +/- 0.05 V/m. The value of the EMF was calculated to be 0.48 +/- 0.05 mG.). Significant (P glutathione and malondialdehyde levels. It is concluded that exposure to the ELF-EMFs for different time periods produced significant decreases in plasma catalase activities in the 3-month exposure groups but no effects on progesterone level, on 17-beta estradiol level, or on the morphology and weight of uterus and ovaries.

  20. Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats

    Directory of Open Access Journals (Sweden)

    Eggett Dennis L

    2008-11-01

    Full Text Available Abstract Background High dietary intake of selenium or isoflavones reduces risk factors for prostate cancer. We tested whether combined supplementation of these two dietary components would reduce prostate cancer risk factors in rats more than supplementation of each component individually. Methods Male Noble rat pups were exposed from conception to diets containing an adequate (0.33–0.45 mg/kg diet or high (3.33–3.45 mg/kg concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg or high (600 mg/kg level of isoflavones in a 2 × 2 factorial design. Pups consumed their respective diets until sacrifice at 35, 100, or 200 days. Male Noble rat breeders, whose exposure to the diets began after puberty, were sacrificed at 336 days. Rats were weighed biweekly. Blood was collected at the time of sacrifice and body fat and prostates were dissected and weighed. Serum levels of leptin, IGF-1, and testosterone were determined using ELISA kits. Serum levels of isoflavones were assayed by GC/MS. Liver activity of selenium-dependent glutathione peroxidase 1 was measured as an indicator of selenium status. Results Serum isoflavone concentrations were nearly 100-fold higher at 35 days of age (1187.1 vs. 14.4 ng/mL, mean ± SD in pups fed the high vs. low isoflavone diets, and remained so at 100 and 200 days, and in breeders. There were no dietary differences in liver glutathione peroxidase activity in pups or breeders. High isoflavone intake significantly (p = 0.001–0.047 reduced body weight in rat pups from 35 days onward, but not in breeders. Body fat and leptin were likewise significantly reduced by high isoflavones in pups while effects in breeders were less pronounced but still significant. High intake of Se and isoflavones each decreased serum IGF-1 in pups at 100 and 200 days, but not in breeders. No consistent dietary effects were observed on serum testosterone or relative weights of prostates. In pups, the combination of high

  1. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

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    Wajdy Al-Awaida

    2014-10-01

    Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.

  2. Quantification of Bone Growth Rate Variability in Rats Exposed to Micro- (near zero G) and Macrogravity (2G)

    Science.gov (United States)

    Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily

    1996-01-01

    Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

  3. Quantitation of Bone Growth Rate Variability in Rats Exposed to Micro-(near zero G) and Macrogravity (2G)

    Science.gov (United States)

    Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily

    1997-01-01

    Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro- (near zero G: e.g., Cosmos 1887 & 2044; SLS-1 & SLS-2) and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

  4. Change of Brain Cellular Mitochondrial Function and Ultrastructure in Offspring Rats Exposed to Arsenic during Gestation and Growth%胚胎期和生长期子代大鼠砷暴露对脑细胞线粒体功能和超微结构的影响

    Institute of Scientific and Technical Information of China (English)

    朱筑霞; 吴泽江; 王旭东; 易必达; 潘玮炜

    2011-01-01

    目的 观察胚胎期和生长期连续砷暴露的仔鼠脑神经细胞线粒体功能和超微结构的变化,探讨砷对子代大鼠脑功能损伤机制.方法 SD大鼠随机分成对照组、低、高砷染毒组,染砷组自由饮用As2O3水溶液,剂量为0.6、15 mg/kg,6周后,各组分别雄雌2∶1合笼产仔,仔鼠由各自染砷母代乳养至断乳后,仔鼠离开母鼠继续本组剂量染砷到6和16周,测定仔鼠脑神经细胞线粒体的呼吸活性和ATP合成量,同时观察线粒体的超微结构变化.结果 断乳后继续染砷6和16周的高、低剂量组仔鼠脑细胞线粒体Ⅲ态呼吸(R3)比对照组明显降低,以高剂量组仔鼠最为显著(P<0.01);呼吸控制率(RCR)在各染砷组都有所降低,但以16周高剂量组仔鼠降低更显著(P<0.05).染砷组的ATP合成量比对照组明显减少,以高砷组仔鼠减少更显著(P<0.01);电镜下染砷组线粒体有基质肿胀,部分嵴减少甚至断裂,高砷组仔鼠还见线粒体外膜断裂,部分线粒体呈空泡样改变,有的甚至溶解.结论 仔鼠在胚胎期与生长发育期连续砷暴露其脑神经细胞线粒体呼吸功能和能量代谢功能均会受到明显损伤,损伤程度有剂量和时间-效应关系.%Objective To investigate the toxic effects of arsenic on brain nerve cellular mitochondrial funct1on and ultrastructure of Fl generation rats exposed to arsenic during gestation and growth. Methods Sprague-Dawley(SD) rats of cleanliness grade were randomly divided into three group (low-, high-dose arsenic group and control group ), treated with arsenic (As2O3) at doses of 10 mg/kg, 0.4 mg/kg, the control group with distilled water, for 6 consecutive weeks. Fl pup rats were lactated by dam exposed arsenic until weaning, Fl pup rats continuously exposed to arsenic for 6 and 16 weeks after weaning respectively. The respiratory activity and ATP amounts of brain cellular mitochondria were determined in all groups and mitochondria

  5. The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate.

    Science.gov (United States)

    Zucki, Fernanda; Morata, Thais C; Duarte, Josilene L; Ferreira, Maria Cecília F; Salgado, Manoel H; Alvarenga, Kátia F

    2017-01-23

    The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400mg/L) and supplemented with ferrous sulfate (20mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r=0.951; pferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100mg/L), but not for the group exposed to the higher concentration (400mg/L). This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. All rights reserved.

  6. Effects of exposing rats to 100% oxygen at 450 and 600 mm Hg on in vitro liver and adipose tissue lipid synthesis.

    Science.gov (United States)

    Feller, D. D.; Neville, E. D.; Talarico, K. S.

    1972-01-01

    Male rats (260-285 gm) were exposed to 100% oxygen at 450 or 600 mm Hg for 1 to 4 days. Rats maintained at 450 mm Hg ate 92% the amount of food eaten by ad libitum controls maintained at sea level conditions. At 600 mm Hg, the food intake was 77% of the ad libitum controls. No difference was found in the plasma level of glucose, free fatty acids, and corticosterone between oxygen exposed rats and their respective pair-fed controls. The in vitro conversion of acetate into fatty acids by adipose tissue from rats exposed at 450 mm Hg for 2, 3, or 4 days was significantly increased above pair-fed controls and ad libitum controls. Increasing the oxygen pressure to 600 mm Hg abolished this increase, and in fact, reversed the increased synthesis to a significant decrease for the 4-day exposure.

  7. [Protective effects of amygdalin on hyperoxia-exposed type II alveolar epithelial cells isolated from premature rat lungs in vitro].

    Science.gov (United States)

    Chang, Li-wen; Zhu, Hua-ping; Li, Wen-bin; Liu, Han-chu; Zhang, Qian-shen; Chen, Hong-bing

    2005-02-01

    To analyze the effect of hyperoxia on the proliferation and surfactant associated protein messenger RNA levels of type II alveolar epithelial cells (AECIIs) of premature rat, and to investigate the effect of amygdalin on the change resulted from hyperoxia in AECIIs isolated from premature rat lung in vitro. The lung tissue of 20-day fetal rat was digested by trypsin and collagenase. AECIIs and lung fibroblasts (LFs) were isolated and purified at different centrifugal force and different adherence, then cultured. The nature of the cultures was identified by cytokeratin staining, vimentin staining and transmission electron micrography. For establishing hyperoxia-exposed cell model, purified AECIIs were cultured for 24 hours after culture flasks were filled with 95% oxygen-5% CO2 at 3 L/min for 10 min, and then sealed. Oxygen concentrations were tested in CYS-1 digital oxygen monitor after 24 hours of exposure. A sample was discarded if its oxygen concentration was amygdalin at various concentrations. DNA content, protein expression of proliferating cell nuclear antigen (PCNA) and mRNA levels of SPs of AECIIs were analyzed with flow cytometric assay, Western blot and reverse transcription polymerase chain reaction (RT-PCR) respectively after 24 hours of air or hyperoxia exposure in the presence or absence of 200 micromol/L amygdalin. Excellent yields of highly purified, culturable AECIIs could be obtained from 20-day fetal lungs. The expression of cytokeratin in AECIIs was positive and that of vimentin negative by immunocytochemistry. Those, however, in LFs were just opposite. Lamellar bodies in purified AECIIs were revealed by transmission electron micrography. The established hyperoxia-exposed cell model assured the oxygen concentrations of culture flasks more than 90%. Amygdalin at the concentration range from 50 micromol/L to 200 micromol/L stimulated the proliferation of AECIIs in a dose-dependent manner; however, at the concentration of 400 micromol/L inhibited

  8. Impairment in Spatial Memory in adult Rats following developmental Low Lead Exposure

    Directory of Open Access Journals (Sweden)

    Rajashekar Rao Barkur

    2012-11-01

    Full Text Available The present study was aimed to investigate the effect of environmentally relevant levels of lead exposure during gestational and early postnatal period on hippocampal dependent spatial memory in rats during adulthood. The pregnant rats were allowed to drink either normal water (control group or 0.2% lead acetate solution (Leadtreated group during pregnancy and lactation. Thus rats pups of lead treated group where exposed to lead indirectly through their mothers during this period. At weaning pups of lead treated group were allowed to drink normal water till they attain the adult hood. Blood lead level was estimated on postnatal day 22 and 120. Birth weight and weight gain of the rat pups as they grew were measured at regular intervals. Both the control and lead treated groups of rats were subjected to water maze test on postnatal day 30 and 120. Results showed that lead treatment had no effect on birth weight or weight gain. Blood lead level on postnatal day 22 was significantly high in treated group compared to the control group and it was normalized by end of four months. The rats born to lead treated mothers showed impaired in spatial memory during water maze test both on postnatal day 36 and 126. These data suggests that exposure to environmentally relevant levels of lead during intrauterine and early postnatal period of brain development causes impairment in spatial memory not only during infancy but also lasts till adulthood.

  9. The effect of neonatal maternal stress on plasma levels of adrenocorticotropic hormone, corticosterone, leptin, and ghrelin in adult male rats exposed to acute heterotypic stressor.

    Science.gov (United States)

    Holubová, A; Štofková, A; Jurčovičová, J; Šlamberová, R

    2016-12-22

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is important for maintenance of homeostasis during stress. Recent studies have shown a connection between the HPA axis and adipose tissue. The present study investigated the effect of acute heterotypic stress on plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), leptin, and ghrelin in adult male rats with respect to neonatal maternal social and physical stressors. Thirty rat mothers and sixty of their male progeny were used. Pups were divided into three groups: unstressed control (C), stressed by maternal social stressor (S), stressed by maternal social and physical stressors (SW). Levels of hormones were measured in adult male progeny following an acute swimming stress (10 min) or no stress. ELISA immunoassay was used to measured hormones. The ACTH and CORT levels were significantly increased in all groups of adult progeny after acute stress; however, CORT levels were significantly lower in both neonatally stressed groups compared to controls. After acute stress, plasma leptin levels were decreased in the C and SW groups but increased in the S group. The data suggest that long-term neonatal stressors lead to lower sensitivity of ACTH receptors in the adrenal cortex, which could be a sign of stress adaptation in adulthood. Acute stress in adult male rats changes plasma levels of leptin differently relative to social or physical neonatal stressors.

  10. Treatment with L-valine ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to carbon tetrachloride.

    Science.gov (United States)

    Nakanishi, Chikashi; Doi, Hideyuki; Katsura, Kazunori; Satomi, Susumu

    2010-06-01

    It has been reported that treatment with branched chain amino acids (BCAAs) increases the survival rates in cirrhotic patients. In this study, we investigated the effect of L-valine, one of BCAAs, on liver fibrosis in rat. To induce liver fibrosis, male Wistar rats were injected carbon tetrachloride (CCl(4)) intraperitoneally (2.0 mL/kg) twice a week for 12 weeks. The rats (seven to fifteen rats for each group) were then administered 1.688 g/kg/day of L-valine intravenously for 7 days or 10% amino acid preparation that provided the same amount of nitrogen. Seven days after the last administration, blood platelet counts and bone marrow megakaryocyte counts were significantly higher in the valine group than in the control group (131.2 +/- 38.3 vs. 106.3 +/- 14.5 x 10(4)/microL, p = 0.04; 18.0 +/- 2.1 vs. 13.5 +/- 2.2 per field, p valine group than the control group. Furthermore, hepatic fibrosis was significantly reduced in the valine group, and the mRNA levels of factors associated with liver fibrosis such as procollagen alpha1(III), transforming growth factor-beta1 and connective tissue growth factor were significantly lower in the liver of the valine group 10 days after the last administration. These results indicate that L-valine treatment ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to CCl(4). Therefore, L-valine supplementation may be helpful for patients with liver cirrhosis.

  11. Regulation of hematopoiesis in rats exposed to antiorthostatic hypokinetic/hypodynamia. II - Mechanisms of the 'anemia'

    Science.gov (United States)

    Dunn, C. D. R.; Johnson, P. C.; Lange, R. D.

    1986-01-01

    The cause of the red cell mass (RCM) deficit, which occurs in rats during suspenion, is investigated. The experimental conditions and procedures, in which male Sprague-Dawley rats are subjected to antiorthostatic hyypokinetic/hypodynamia and changes in RCM are monitored, are described. The influences of stress, reduced food and water consumption, and antiorhostatic posture on RCM are analyzed. Changes in body weight, RCM, radioiron incorporation, red blood cells (RBC), and reticulocytes, for the rats after head-down suspension are graphically presented; only the changes in RBC are related to the antiorthostatic posture. The data reveal that anemia is primarily caused by reduced food and water consumption and secondly by restricted movements.

  12. [Protective effect of hypothermia on brain neurons of rats exposed to ionizing radiation].

    Science.gov (United States)

    Gordon, R Ia; Ignat'ev, D A; Mel'nikova, E B; Rogachevskiĭ, V V; Kraev, I V; Hutsian, S S

    2007-01-01

    The conditions of the protein-synthesizing system in neurons of the hippocampus (areas CA1 and C A3) and of the cortex (sensomotor region) in rats subjected to y-irradiation at a dose of 8 Gy under hypothermia (16 - 18 degrees C) and hypoxia-hypercapnia were investigated by fluorescent and electron microscopy. Under hypothermia, the protein-synthesizing system was shown to be damaged to a lesser degree and to be restored faster in comparison with similar neurons in rats irradiated at room temperature. In rats irradiated under hypothermia, the rRNA biogenesis and the protein-synthesizing activity of polyribosomes were restored in two days. The protective influence of hypothermia did not spread to changes in membrane structures (endoplasmic reticulum and Golgy apparatus); i.e., a partial loss of integrity and possible transformation of their structure caused by the irradiation and the restoration of these structures occurred at a lower rate.

  13. Cerebral microbleeds in a neonatal rat model

    Science.gov (United States)

    Carusillo Theriault, Brianna; Woo, Seung Kyoon; Karimy, Jason K.; Keledjian, Kaspar; Stokum, Jesse A.; Sarkar, Amrita; Coksaygan, Turhan; Ivanova, Svetlana; Gerzanich, Volodymyr

    2017-01-01

    Background In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes) dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter. Methods Pregnant Wistar rats were subjected to intrauterine ischemia (IUI) and low-dose maternal lipopolysaccharide (mLPS) at embryonic day (E) 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks. Results mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2) and protein (CD31, MMP2, MMP9) for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls. Conclusions In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development. PMID:28158198

  14. Neuroprotective Mechanisms Activated in Non-seizing Rats Exposed to Sarin

    Science.gov (United States)

    2015-06-04

    Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States a r t i c l e i n f o Article history : Accepted...Paniagua, C., Vacas, E., Fernández, B., 2007. Effect of ammonia , glutamine, and serum on calcineurin, p38MAPK-diP, GADD153/CHOP10, and CNTF in primary rat...T., Ishikura, T., Fujihara, H., Nomura, M., Hachisuka, K., Ueta, Y., 2011. Upregulation of arginine vasopressin synthesis in the rat hypothalamus

  15. Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

    Directory of Open Access Journals (Sweden)

    Anwesha eBanerjee

    2014-11-01

    Full Text Available Autism Spectrum Disorders (ASD are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning.

  16. Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero.

    Science.gov (United States)

    Banerjee, Anwesha; Engineer, Crystal T; Sauls, Bethany L; Morales, Anna A; Kilgard, Michael P; Ploski, Jonathan E

    2014-01-01

    Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning.

  17. Prenatal Exposure to 1-Bromopropane Suppresses Kainate-Induced Wet Dog Shakes in Immature Rats.

    Science.gov (United States)

    Fueta, Yukiko; Kanemitsu, Masanari; Egawa, Sumie; Ishidao, Toru; Ueno, Susumu; Hori, Hajime

    2015-12-01

    1-Bromopropane (1-BP) is used in degreasing solvents and spray adhesives. The adverse effects of 1-BP have been reported in human cases and adult animal models, and its developmental toxicity has also been reported, but its effects on developmental neurotoxicity have not been investigated in detail. We evaluated the effects in rat pups of prenatal exposure to 1-BP on behaviors such as scratching and wet dog shakes (WDS), which were induced by injection of kainate (KA). Pregnant Wistar rats were exposed to vaporized 1-BP with 700 ppm from gestation day 1 to day 20 (6 h/day). KA at doses of 0.1, 0.5, and 2.0 mg/kg were intraperitoneally injected into a control group and a 1-BP-exposed group of pups on postnatal day 14. There was no significant difference in scratching between the control and the prenatally 1-BP-exposed groups, while suppression of the occurrence ratio of WDS was observed at the low dose of 0.1 mg/kg of KA in the prenatally 1-BP-exposed pups. Our results suggest that prenatal exposure to 1-BP affects neurobehavioral responses in the juvenile period.

  18. L-DEPRENYL REDUCES BRAIN-DAMAGE IN RATS EXPOSED TO TRANSIENT HYPOXIA-ISCHEMIA

    NARCIS (Netherlands)

    KNOLLEMA, S; AUKEMA, W; HOM, H; KORF, J; TERHORST, GJ

    1995-01-01

    Background and Purpose L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model. Metho

  19. Maternal and fetal toxicity of Wistar rats exposed to herbicide metolachlor

    Directory of Open Access Journals (Sweden)

    Kátia Cristina de Melo Tavares Vieira

    2016-07-01

    Full Text Available Metolachlor is a selective pre-emergent herbicide widely used in agriculture to control weeds. The aim of this study was to evaluate the possible effects of metolachlor on reproductive performance of adult rats, as well as its teratogenic potential when administered during the period of organogenesis. Pregnant adult female rats were allocated into 4 experimental groups (n = 10 group-1, that received 0 (control; 150 (TA; 300 (TB; or 1000 mg kg-1 bw day-1 (TC of metolachlor, by gavage, from the 6th to 15th gestational day (GD. There is reduction in the weight gain of the animals from TB and TC groups compared to the control group. Liver and placenta weights were reduced in TB and TC groups, respectively, while the percentage of post-implantation loss was increased in the TC group. There were no external malformations in either rat of the control or treated groups. However, an increased incidence of skeletal anomalies and visceral anomalies (especially in the urogenital system was observed in TC group. These results demonstrate that exposure of pregnant rats to metolachlor can lead to signs of general toxicity, late embryonic losses and congenital anomalies.

  20. EVALUATION OF SENSORY EVOKED POTENTIALS IN LONG EVANS RATS GESTATIONALLY EXPOSED TO MERCURY (HGO) VAPOR.

    Science.gov (United States)

    Human exposure to mercury vapor (Hg0) has been reported to result in sensory disturbances. Developmental exposure to toxicants may result in long-lasting changes in neural function. This manuscript describes the lack of effect of gestational exposure of Long Evans rats to Hg0 on ...

  1. Peripheral effect of NMDA receptor antagonists on adult rats exposed to neonatal colon pain

    Institute of Scientific and Technical Information of China (English)

    ChunLin; ElieD.Al-Chaer

    2004-01-01

    AIM: Previous work done by Al-Chaer' s lab has shown that colon irritation (CI) in neonates can lead to chronic visceral hypersensitivity in adult rats, with characteristics of visceral allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology (Al-Chaer et al. 2000) . The pathogenesis of

  2. Physical provocation of pubertal anabolic androgenic steroid exposed male rats elicits aggression towards females.

    Science.gov (United States)

    Cunningham, Rebecca L; McGinnis, Marilyn Y

    2006-09-01

    Human studies suggest that anabolic androgenic steroid (AAS) users are aggressive towards women. This study used a rat model to evaluate whether AAS potentiated aggression towards females and the conditions under which this occurs. Gonadally intact pubertal male rats received one of the following AAS treatments (5 mg/kg s.c. 5 days/week for nine weeks): testosterone (T), stanozolol (S), testosterone + stanozolol (T + S), or vehicle control. Each rat was tested with 3 conspecific stimuli: ovariectomized females (OVX), estrogen only females (E), and estrogen + progesterone females (E + P). The response to physical provocation was tested under three conditions: without physical provocation, provocation of the experimental male, and provocation of the conspecific female. Provocation was a mild tail pinch. Both aggressive and sexual behaviors were measured during each test. In the absence of physical provocation, AAS males were not aggressive towards females. However, provocation significantly increased aggression in males treated with testosterone but only towards OVX females. In the presence of E or E + P females, all animals displayed sex behavior, not aggression. Thus, factors such as the nature of the AAS and the hormonal status of the females are important in determining whether male rats will be aggressive towards females. However, the most salient factor determining aggression towards females is the presence of provocation in combination with high levels of testosterone.

  3. Responses of testis, epididymis, and sperm of pubertal rats exposed to functionalized multiwalled carbon nanotubes.

    Science.gov (United States)

    Farombi, Ebenezer O; Adedara, Isaac A; Forcados, Gilead E; Anao, Osemudiamen O; Agbowo, Agatha; Patlolla, Anita K

    2016-05-01

    The present study investigated the response of testes, epididymides and sperm in pubertal Wistar rats following exposure to 0, 0.25, 0.5, 0.75, and 1.0 mg kg(-1) functionalized multi-walled carbon nanotubes (f-MWCNTs) for 5 days. The results showed that administration of (f-MWCNTs) significantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner in both testes and sperm compared with control group. Moreover, the significant decrease in the activity of glutathione-S-transferase and glutathione level was accompanied with significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm of (f-MWCNTs)-treated rats. The spermiogram of (f-MWCNTs)-treated rats indicated significant decrease in epididymal sperm number, sperm progressive motility, testicular sperm number and daily sperm production with elevated sperm abnormalities when compared with the control. Exposure to (f-MWCNTs) decreased plasma testosterone level and produced marked morphological changes including decreased geminal epithelium, edema, congestion, reduced spermatogenic cells and focal areas of tubular degeneration in the testes. The lumen of the epididymides contained reduced sperm cells and there was mild to severe hyperplasia epithelial cells lining the duct of the epididymis. Collectively, pubertal exposure of male rats to (f-MWCNTs) elicited oxidative stress response resulting in marked testicular and epididymides dysfunction.

  4. Protective Effects of Zinc Supplementation on Renal Toxicity in Rats Exposed to Cadmium

    Directory of Open Access Journals (Sweden)

    Morshedi

    2014-07-01

    Full Text Available Background Cadmium (Cd is a nonessential element with many industrial applications and is one of the most toxic pollutants in the environment. The ultimate goal of occupational health is prevention of health hazards on workplace; hence, is as a hazardous chemical contaminant in the workplace, Cd needs special attention. Objectives The object of this study was to determine the effect of ZnCl2 on Cd-induced nephrotoxicity in rats. Materials and Methods Adult male rats were given CdCl2 at doses of 0, 1, 2, and 3 mg/kg. Another series of rats were pretreated with 4 mg/kg of ZnCl2 30 minutes prior to administration of various doses of CdCl2. The experiment was repeated for seven consecutive days. Twenty-four hours after administering the latest dose, animals were sacrificed. Blood samples were analyzed for blood urea nitrogen (BUN and creatinine levels. Kidney tissues were excised for measuring malondialdehyde (MDA concentration. Results In contrast to the animals that received ZnCl2, CdCl2 induced a dose-dependent elevation in BUN, creatinine, and MDA in those without ZnCl2 pretreatment. Zinc chloride had significantly decreased all biochemical parameters and protected kidney cells against Cd-induced toxicity. Conclusions The results of this study supported the potential protective effects of ZnCl2 on rat kidney tissues against CdCl2 toxicity.

  5. Differential cardiac effects in rats exposed to atmospheric smog generated from isoprene versus toluene

    Science.gov (United States)

    The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a comple...

  6. Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone

    Science.gov (United States)

    We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH ...

  7. DNA lesion and Hprt mutant frequency in rat lymphocytes and V79 Chinese hamster lung cells exposed to cadmium.

    Science.gov (United States)

    Jianhua, Zhou; Lian, Xue; Shuanlai, Zheng; Juan, Du; Shuanxi, Yang

    2006-03-01

    Cadmium is a potential carcinogenic environmental and occupational pollutant. A wide variety of mutagens have been shown to cause DNA damage, but it is not yet clear whether the DNA damage is relative to inducement of mutations. DNA damage and the formation of mutations at the hypoxanthine guanine phosphoribosyl trans ferase (HPRT) induced by cadmium chloride (CdCl(2)) were investigated with rat lymphocytes and V79 Chinese hamster lung cells. The hprt mutant frequency (MF) assay was used as the method to measure gene mutation in the rat lymphocytes and V79 cells exposed to CdCl(2), and comet assay analysis was performed to detect DNA lesion and repair in CdCl(2)-induced V79 cells. The results showed that CdCl(2) treatment caused a strong genotoxic effect and a marginal effect on the frequency of gene mutations. The hprt mutant frequencies in the rat lymphocytes and V79 cells exposed to CdCl(2) were statistically higher than those of the negative control. There was statistical significance in TL, TD and percentage of comet cell with tails. CdCl(2) treatment can induce DNA single-strand breaks. There was a dose-dependent increase between CdCl(2) and DNA lesion. After cells were treated with CdCl(2) and hydrogen peroxide (H(2)O(2)), the TL and TD declined with repair time increasing, which indicated that DNA damages were repaired gradually. However, DNA repair with treatment of CdCl(2) was slower than that of H(2)O(2) in V79 cells, which suggests that CdCl(2) affected DNA repair of damaged cells. The study also showed that the hprt MF and comet assay can be used for genotoxicity testing of heavy metals. DNA damage detected with the comet assay may be relative to mutagenesis.

  8. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

    Directory of Open Access Journals (Sweden)

    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  9. Protective effect of alpha-lipoic acid, aerobic or resistance exercise from colitis in second hand smoke exposed young rats.

    Science.gov (United States)

    Özbeyli, Dilek; Berberoglu, Ayşe Cansu; Özen, Anıl; Erkan, Oktay; Başar, Yunus; Şen, Tunahan; Akakın, Dilek; Yüksel, Meral; Kasımay Çakır, Özgür

    2017-01-01

    The role of second hand smoke (SHS) exposure on ulcerative colitis is not known. Our aim was to examine the effects of α-lipoic acid (ALA), chronic aerobic (AE) or resistance exercise (RE) on SHS exposed rats with colitis. Sprague-Dawley male rats (150-200 g, n=54) were selected for colitis induction. Among the colitis groups, one group was exposed to SHS (6 d/wk, 4 cigarettes/d) and the other was not. The SHS group was divided into subgroups as follows: sedentary; AE (swimming; 3 d/wk); and RE (climbing with weight; 3 d/wk). After 5 weeks, colitis was induced by intrarectal acetic acid. All groups had subgroups that were given subcutaneously ALA (50 mg/kg per day) or vehicle for 3 days. Following decapitation, colon tissues were sampled to examine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminenscence, macroscopic scoring and histologic examination. ANOVA and Student's t-test were used for statistical analysis. The increased macroscopic and microscopic scores, MPO, MDA, luminol and lucigenin measurements in colitis and SHS-colitis groups were decreased via ALA (Pcolitis and SHS-colitis groups (Pcolitis. Decreased GSH levels (Pcolitis group approached to control levels when given ALA. According to our results SHS and colitis induction increased inflammatory damage. SHS did not worsen it more than colitis. Our results suggest that ALA, AE or RE might be protective for SHS exposed ulcerative colitis conditions. © 2016 John Wiley & Sons Australia, Ltd.

  10. Influence of perinatal trans fat on behavioral responses and brain oxidative status of adolescent rats acutely exposed to stress.

    Science.gov (United States)

    Pase, C S; Roversi, Kr; Trevizol, F; Roversi, K; Kuhn, F T; Schuster, A J; Vey, L T; Dias, V T; Barcelos, R C S; Piccolo, J; Emanuelli, T; Bürger, M E

    2013-09-01

    Because consumption of processed foods has increased in the last decades and so far its potential influence on emotionality and susceptibility to stress is unknown, we studied the influence of different fatty acids (FA) on behavioral and biochemical parameters after acute restrain stress (AS) exposure. Two sequential generations of female rats were supplemented with soybean oil (control group; C-SO), fish oil (FO) and hydrogenated vegetable fat (HVF) from pregnancy and during lactation. At 41days of age, half the animals of each supplemented group were exposed to AS and observed in open field and elevated plus maze task, followed by euthanasia for biochemical assessments. The HVF-supplemented group showed higher anxiety-like symptoms per se, while the C-SO and FO groups did not show these behaviors. Among groups exposed to AS, HVF showed locomotor restlessness in the open field, while both C-SO and HVF groups showed anxiety-like symptoms in the elevated plus maze, but this was not observed in the FO group. Biochemical evaluations showed higher lipoperoxidation levels and lower cell viability in cortex in the HVF group. In addition, HVF-treated rats showed reduced catalase activity in striatum and hippocampus, as well as increased generation of reactive species in striatum, while FO was associated with increased cell viability in the hippocampus. Among groups exposed to AS, HVF increased reactive species generation in the brain, decreased cell viability in the cortex and striatum, and decreased catalase activity in the striatum and hippocampus. Taken together, our findings show that the type of FA provided during development and growth over two generations is able to modify the brain oxidative status, which was particularly adversely affected by trans fat. In addition, the harmful influence of chronic consumption of trans fats as observed in this study can enhance emotionality and anxiety parameters resulting from stressful situations of everyday life, which can

  11. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jang, Won-Suk; Lee, Sun-Joo [Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Lee, Seung-Sook [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Sunhoo, E-mail: sunhoo@kcch.re.kr [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  12. The effect and mechanism of action of carbocysteine on airway bacterial load in rats chronically exposed to cigarette smoke.

    Science.gov (United States)

    Sun, Li; Tang, Lifeng; Xu, Yan; Wang, Shouqin; Li, Yaming; Kang, Jian

    2010-10-01

    Carbocysteine (S-carboxymethylcysteine) is a mucoactive drug with in vitro free radical scavenging and anti-inflammatory properties. Several clinical trials have indicated that carbocysteine reduces exacerbation rates in COPD. In the present study, the effect of carbocysteine on the airway load of Haemophilus influenzae was assessed in rats chronically exposed to cigarette smoke (CS). In addition, the effects of carbocysteine on airway mucus hypersecretion and mucociliary clearance (MCC) associated with the adherence and clearance of H. influenzae were investigated. Wistar rats were randomly divided into control, carbocysteine vehicle, CS exposure and carbocysteine treatment groups. After 12 weeks, rats were selected for quantitative inoculation of H. influenzae. BAL fluid and lungs were collected aseptically after 3 h for quantitative culture of H. influenzae. MCC was measured by quantifying the clearance of (99m)Tc-Sc. Goblet cell metaplasia and the presence of mucoid matter were evaluated by Alcian blue/periodic acid-Schiff staining. Mucin 5AC (Muc5AC) expression was detected by western blotting and real-time reverse transcription-PCR. Exposure to CS increased airway H. influenzae load, aggravated mucus hypersecretion and delayed MCC. Treatment with carbocysteine decreased airway H. influenzae load, and attenuated airway mucus hypersecretion, with improved MCC associated with adherence and clearance of H. influenzae. These results suggest that carbocysteine may be beneficial in patients with COPD by increasing the clearance of bacteria and decreasing bacterial load. © 2010 The Authors. Respirology © 2010 Asian Pacific Society of Respirology.

  13. Physiological and histopathological changes in the liver of male rats exposed to paracetamol and diazinon

    Institute of Scientific and Technical Information of China (English)

    Abdel-Tawab H Mossa; Tarek M Heikal; Enayat Abdel Aziz Omara

    2012-01-01

    Objective: The present study was conducted to evaluate the adverse effect of exposure to Diazinon (DIA) and Paracetamol (PARA) and their combination on male rats. Methods: Rats were orally administered PARA at a dose of 66.66 mg a.i. kg-1 body weight (maximum administration dose) and DIA at a dose 12.50 mg a.i. kg-1 b.wt. (1/100 LD50) for 28 consecutive days. Results:Significantly, decreased of body weights were observed in all treated groups, while significant increase in relative liver weight were recorded in DIA and DIA+PARA-treated groups compared to control rats. Liver dysfunction enzymes (e.g., aspartate aminotransferase, AST; alanine aminotransferase, ALT; alkaline phosphatase, ALP and lactate dehydrogenase, LDH) and Lipid Peroxidation Level (LPO) were increased in DIA, PARA and DIA+PARA-treated groups. Treatment of DIA and DIA+PARA caused significant decrease in the activity of serum Cholinesterase (ChE). PARA, DIA and PARA+DIA treatments caused histopathological changes and decreases in DNA content in liver cells of rats. The severities of such observations were more pronounced in their combined exposure. Conclusions: We can conclude that both paracetamol at maximum administration dose and diazinon caused biochemical and histopathological alteration in the liver of male rats. The severities of such observations were more pronounced in their combined exposure. The data throw light on the problem of simultaneous exposure to OPIs and commonly used drugs especially among agriculture sector workers in developing countries, where the handling of drugs (e.g., PARA) is mainly without medical prescription. Further studies, applied to pregnant women, newborns and childhood may be of great significance.

  14. PATTERN OF CHOLINESTERASE INHIBITION IN ADULT, MALE RATS CHRONICALLY EXPOSED TO DIETARY CHLORPYRIFOS.

    Science.gov (United States)

    Very little is known about the effects of chronic exposure to relatively low levels of anticholinesterase insecticides or how the effects of chronic exposure compare to higher, intermittent exposure of the same compound for the same duration. To that end, we exposed adult male ra...

  15. Assessment of genotoxic and cytotoxic hazards in brain and bone marrow cells of newborn rats exposed to extremely low-frequency magnetic field.

    Science.gov (United States)

    Rageh, Monira M; El-Gebaly, Reem H; El-Bialy, Nihal S

    2012-01-01

    The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF) and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery) were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA) and the activity of glutathione (GSH) and superoxide dismutase (SOD). The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P < 0.01, 0.001, 0.0001). Moreover ELF-MF exposure induced a significant (P < 0.01, 0.001) four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P < 0.0001). Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P < 0.05). Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats.

  16. Assessment of Genotoxic and Cytotoxic Hazards in Brain and Bone Marrow Cells of Newborn Rats Exposed to Extremely Low-Frequency Magnetic Field

    Directory of Open Access Journals (Sweden)

    Monira M. Rageh

    2012-01-01

    Full Text Available The present study aimed to evaluate the association between whole body exposure to extremely low frequency magnetic field (ELF-MF and genotoxic , cytotoxic hazards in brain and bone marrow cells of newborn rats. Newborn rats (10 days after delivery were exposed continuously to 50 Hz, 0.5 mT for 30 days. The control group was treated as the exposed one with the sole difference that the rats were not exposed to magnetic field. Comet assay was used to quantify the level of DNA damage in isolated brain cells. Also bone marrow cells were flushed out to assess micronucleus induction and mitotic index. Spectrophotometric methods were used to measure the level of malondialdehyde (MDA and the activity of glutathione (GSH and superoxide dismutase (SOD. The results showed a significant increase in the mean tail moment indicating DNA damage in exposed group (P<0.01,0.001,0.0001. Moreover ELF-MF exposure induced a significant (P<0.01,0.001 four folds increase in the induction of micronucleus and about three folds increase in mitotic index (P<0.0001. Additionally newborn rats exposed to ELF-MF showed significant higher levels of MDA and SOD (P<0.05. Meanwhile ELF-MF failed to alter the activity of GSH. In conclusion, the present study suggests an association between DNA damage and ELF-MF exposure in newborn rats.

  17. Furin mediates brain-derived neurotrophic factor upregulation in cultured rat astrocytes exposed to oxygen-glucose deprivation.

    Science.gov (United States)

    Chen, Yan; Zhang, Junjian; Deng, Min

    2015-01-01

    This study investigated the changes in brain-derived neurotrophic factor (BDNF) expression and the role of furin in BDNF maturation in reactive astrocytes from rats exposed to oxygen-glucose deprivation (OGD). Furin, a proprotein convertase, is upregulated and cleaves certain substrates during hypoxia in cancer cells. In addition, during hypoxia in the central nervous system, astrocytes become reactive and release BDNF to protect neurons. Maturation of BDNF in astrocytes requires furin-mediated endoproteolytic processing of the precursor protein pro-BDNF to BDNF. To expand our knowledge about the role of furin in BDNF maturation in astrocytes, these cells were exposed to OGD, and expression of furin and BDNF was detected by Western blot analysis. Changes in BDNF expression were observed when furin activity was inhibited by furin prosegment. We found that protein expression of BDNF and furin was upregulated, and this upregulation correlated with OGD stimulation. Furin inhibition reduced BDNF maturation and secretion. These results indicate that furin mediates the upregulation of BDNF in reactive astrocytes exposed to OGD and that furin may impact the biological effect of reactive astrocytes.

  18. Lysine acetylsalicylate ameliorates lung injury in rats acutely exposed to paraquat

    Institute of Scientific and Technical Information of China (English)

    HUANG Wei-dong; WANG Jie-zan; LU Yuan-qiang; DI Ya-min; JIANG Jiu-kun; ZHANG Qin

    2011-01-01

    Background Paraquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate (LAS) could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection.Methods A model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ+LAS groups, with 25 in each group. We assessed and compared the malonaldehyde (MDA) content, superoxide dismutase activity (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) in serum and lung and the hydroxyproline (HYP)content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21after PQ poisoning and LAS treatment.Results Compared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning (all P<0.05).After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced.Conclusion In this rat model of PQ poisoning, LAS effectively ameliorated the lung

  19. Warmth from skin-to-skin contact with mother is essential for the acquisition of filial huddling preference in preweanling rats.

    Science.gov (United States)

    Kojima, Sayuri; Alberts, Jeffrey R

    2011-12-01

    During a single, 2-hr session with a scented foster dam, preweanling rat pups form an affiliative attraction to an odor associated with the maternal caregiver, manifest as a huddling preference. To identify maternal stimuli that induce this filial preference, we quantitatively examined behavioral interactions during odor conditioning. Bout duration of skin-to-skin (STS) contact was positively associated with the preference. In contrast, simple physical contact and anogenital licking were not significantly related to the preference. The frequency of nonanogenital licking was negatively associated with the preference as well as with bout duration of STS contact. When odor conditioning was conducted with a warm cylinder, ambient warmth, or stroking as the unconditioned stimulus, only pups exposed to the warm cylinder exhibited a preference for the conditioned odor. These results suggest a positive, affiliative effect of maternal STS contact on pup filial preference, which may be disrupted by maternal licking.

  20. Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery

    DEFF Research Database (Denmark)

    Ibrahim, Rami Mossad; Krammer, Caspar Weel; Hansen, Tom Giedsing

    2015-01-01

    BACKGROUND: Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence...... in experimental groups receiving dexmedetomidine, while propofol administration was associated with increased systemic lactate levels and metabolic acidosis. A substantial difference in anaesthesia/surgery-induced neuroapoptosis was found between young and adult rats in several brain regions. Combination...... and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase-3 profiles were detected between experimental groups...

  1. Diazinon concentrations and blood cholinesterase activities in rats exposed to diazinon.

    Science.gov (United States)

    Tomokuni, K; Hasegawa, T

    1985-04-01

    The tissue distribution of diazinon and the inhibition of blood cholinesterase (ChE) activity were investigated in male rats which received a single intraperitoneal (i.p.) dose of diazinon (100 mg/kg body wt) in olive oil. Diazinon concentration in the blood reached a maximum 1-2 h after dosing. Comparing the distribution of diazinon among liver, kidney and brain in treated rats, the diazinon residue was much greater in the kidney than in other organs, being 500 times that in the liver and 11 times that in the brain at 8 h after dosing. Erythrocyte and plasma ChE activities were inhibited rapidly, but ChE inhibition was greater in the erythrocytes than in plasma.

  2. Assessment of neurotoxic effects and brain region distribution in rat offspring prenatally co-exposed to low doses of BDE-99 and methylmercury.

    Science.gov (United States)

    Zhao, Wenchang; Cheng, Jinping; Gu, Jinmin; Liu, Yuanyuan; Fujimura, Masatake; Wang, Wenhua

    2014-10-01

    Exposure to polybrominated diphenyl ether (PDBE) and methylmercury (MeHg) can occur simultaneously as both contaminants are found in the same food sources, especially fish, seafood, marine mammals and milk. The aim of this study was to assess the effects of exposure to low levels of MeHg (2.0 μg mL(-1) in drinking water) and BDE-99 (0.2 mg kg(-1) d(-1)) from gestational day 6 to postnatal day (PND) 21, alone and in combination, on neurobehavioral development and redox responses in offspring. The present study demonstrated an interaction due to co-exposure with low doses of MeHg and BDE-99 enhanced developmental neurotoxic effects. These effects were manifested as the delayed appearance of negative geotaxis reflexes, impaired motor coordination, and induction of oxidative stress in the cerebellum. In particular, the cerebellum may be a sensitive target for combined MeHg and BDE-99 toxicity. The neurotoxicity of low dose MeHg was exacerbated by the presence of low dose of BDE-99. It is concluded that prenatal co-exposure to MeHg and BDE-99 causes oxidative stress in the cerebellum of offspring by altering the activity of different antioxidant enzymes and producing free radicals. Hg retention was not affected by co-exposure to BDE-99. However, MeHg co-exposure seemed to increase BDE-99 concentrations in selected brain regions in pups compared to pups exposed to BDE-99 only. These results showed that the adverse effects following prenatal co-exposure to MeHg and BDE-99 were associated with tissue concentrations very close to the current human body burden of this persistent bioaccumulative compound.

  3. Oxidative damage and histopathological changes in lung of rat chronically exposed to nicotine alone or associated to ethanol.

    Science.gov (United States)

    Dhouib, H; Jallouli, M; Draief, M; Bouraoui, S; El-Fazâa, S

    2015-12-01

    Smoking is the most important preventable risk factor of chronic obstructive pulmonary disease and lung cancer. This study was designed to investigate oxidative damage and histopathological changes in lung tissue of rats chronically exposed to nicotine alone or supplemented with ethanol. Twenty-four male Wistar rats divided into three groups were used for the study. The nicotine group received nicotine (2.5mg/kg/day); the nicotine-ethanol group was given simultaneously same dose of nicotine plus ethanol (0.2g/kg/day), while the control group was administered only normal saline (1 ml/kg/day). The treatment was administered by subcutaneous injection once daily for a period of 18 weeks. Chronic nicotine administration alone or combined to ethanol caused a significant increase in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and catalase (CAT) activity in lung tissue compared to control rats suggesting an oxidative damage. However, these increases were mostly prominent in nicotine group. The histopathological examination of lung tissue of rats in both treated groups revealed many alterations in the pulmonary structures such as emphysema change (disappearance of the alveolar septa, increased irregularity and size of air sacs) and marked lymphocytic infiltration in perivascular and interstitial areas. However, the changes characterized in the nicotine group (pulmonary congestion, hemorrhage into alveoli and interstitial areas, edema) were more drastic than those observed in the nicotine-ethanol group, and they can be attributed to a significant degree of capillary endothelial permeability and microvascular leak. Conversely, the ethanol supplementation caused an appearance of fatty change and fibrosis in pulmonary tissue essentially due to a metabolism of ethanol. Finally, the lung damage illustrated in nicotine group was more severe than that observed in the nicotine-ethanol group. We conclude that the combined administration of nicotine and ethanol

  4. Effect of tocopherol and acetylsalicylic acid on the biochemical indices of blood in dioxin-exposed rats.

    Science.gov (United States)

    Rosińczuk, Joanna; Całkosiński, Ireneusz

    2015-07-01

    New sources of dioxins and increased dioxin concentrations in the environment, coupled with their increased bioavailability along the food chain and accumulation in adipose tissues, contribute to various adverse long-term biological effects. The purpose of the study was to determine whether tocopherol protects the CNS by decreasing the pro-inflammatory influence of free radicals generated by TCDD; whether acetylsalicylic acid inhibits the production of inflammatory mediators; and whether the combined administration of tocopherol and acetylsalicylic acid to TCDD-exposed rats has a potential CNS-protective effect. The study included 117 rats divided into 8 groups: 75 female and 12 male Buffalo rats aged 8-10 weeks, weighing 140-160 g; as well as 30 female rats aged 6 weeks and weighing 120 g, which were the offspring of females from each study group. In the experiment, the following substances were used: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dosed at 5 μg/kg BW and 12.5 μg/kg BW, diluted in a 1% DMSO solution at the concentration of 1 μg/ml; α-tocopherol acetate, dosed at 30 mg/kg BW, in 0.2 ml of oil solution; and acetylsalicylic acid, 50mg/kg BW, suspended in 0.5 ml of starch solution, administered orally using a feeding tube. Pleurisy was induced by an injection of 0.15 ml of 1% carrageenin solution. The use of tocopherol reduces the adverse effects of the inflammatory reaction induced by TCDD. Administering tocopherol improves protein metabolism by reducing protein catabolism, and raises γ-globulin fraction levels. Combined acetylsalicylic acid and tocopherol suppress catabolic processes accompanying inflammation.

  5. Serotonin transporter in lymphocytes of rats exposed to physical restraint stress.

    Science.gov (United States)

    Medina-Martel, Matilde; Urbina, Mary; Fazzino, Fili; Lima, Lucimey

    2013-01-01

    Glucocorticoids and stress cause transcriptional and functional changes on the serotonin transporter (SERT) in the central nervous system. Stress can produce specific modifications of SERT in lymphocytes, which could be associated with alterations in immune response. The aim of this study was to evaluate the effect of a physical restraint stress protocol on (1) rat lymphocyte proliferation in the presence of the selective serotonin reuptake inhibitor fluoxetine and (2) SERT kinetic parameters, i.e. binding capacity (Bmax), affinity (Kd) and Hill coefficient (nH). Male adult Sprague-Dawley rats were placed in Plexiglass boxes (5 h daily for 5 days), and blood was obtained by cardiac puncture on day 6. Serum corticosterone was quantitated by an immunoenzymatic assay. Lymphocytes were isolated by density gradients and adhesion to plastic, of which there was sufficient material for further experiments, then cultured with or without the mitogen concanavalin A (Con A, 2 μg/ml) and fluoxetine (1-50 μM). Cell proliferation was measured with tetrazolium salts, and [(3)H]paroxetine was used as a SERT-specific ligand for binding assays. Restraint produced a significant increase in serum corticosterone of stressed rats. The proliferative response to Con A was similar in the controls and stressed animals. Fluoxetine reduced cell proliferation with and without Con A. Restraint diminished the inhibitory effect of fluoxetine on proliferation. Restraint also increased Bmax and Kd, but decreased nH. Treatment of rats with actinomycin D, a transcription inhibitor, reduced Bmax in stressed animals. Restraint stress modulated the effect of fluoxetine on cell proliferation, probably through the modification of the presence and the function of SERT. Copyright © 2013 S. Karger AG, Basel.

  6. Determination of LCt50s in Anesthetized Rats Exposed to Aerosolized Nerve Agents

    Science.gov (United States)

    2013-01-01

    REPORT NUMBER US Army Medical Research Institute of Chemical Defense ATTN: MCMR-CDT-N 3100 Ricketts Point Road Aberdeen Proving Ground, MD...SOCES!CEAN Cannon Air Force Base, NM 88103, USA and 2United States Army Medical Research Institute of Chemical Defense Analytical Toxicology Division...xylazine (10  mg/kg) intramuscular injec- tions. Rats were intubated with a 10–12 gauge fire- polished glass Pasteur pipette that was secured with a gauze

  7. Histomorphometric study of tibia of rats exposed aboard American Spacelab Life Sciences 2 Shuttle Mission

    Science.gov (United States)

    Durnova, G.; Kaplansky, A.; Morey-Holton, E.

    1996-01-01

    Tibial bones of rats flown onboard the SLS-2 shuttle mission were studied. Trabecular bone parameters were investigated, including growth plate height, trabecular bone volume, thickness and number, and trabecular separation in the primary and secondary spongiosa. Several histomorphometric changes were noted, allowing researchers to conclude that exposure to microgravity resulted in osteopenia of spongy bone of tibial metaphysis. The roles of bone formation and bone resorption are discussed.

  8. Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats

    DEFF Research Database (Denmark)

    Boberg, Julie; Christiansen, Sofie; Petersen, Marta Axelstad

    2011-01-01

    studied.Pregnant Wistar rats were gavaged from gestation day 7 to postnatal day (PND) 17 with vehicle, 300, 600, 750 or 900mg DINP/kg bw/day.In fetal testes histopathological effects typical of phthalates were observed. In male offspring, DINP caused increased nipple retention, reduced anogenital distance......-androgenic effects on reproductive development, though less potent than DEHP, DBP and BBP, and further safety evaluation of DINP appears warranted....

  9. Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation.

    Science.gov (United States)

    Kutanis, Dilek; Erturk, Engin; Besir, Ahmet; Demirci, Yucel; Kayir, Selcuk; Akdogan, Ali; Vanizor Kural, Birgul; Bahat, Zumrut; Canyilmaz, Emine; Kara, Hanife

    2016-11-01

    To investigate the effects of dexmedetomidine on oxidative injury caused by ionizing radiation. Randomized controlled experimental study. Department of radiation oncology and research laboratory of an academic hospital. Twenty-eight rats were randomized to 4 groups (n=7 per group). Group S rats were administered physiologic serum; group SR rats were administered physiologic serum and 10 Gy external ionizing radiation. Groups D100 and D200 were administered 100 and 200 μg/kg dexmedetomidine intraperitoneally, respectively, 45 minutes before ionizing radiation. Liver, kidney, lung, and thyroid tissue and serum levels of antioxidant enzymes (glutathione peroxidase [GPX], superoxide dismutase, and catalase) and oxidative metabolites (advanced oxidation protein products, malondialdehyde, and nitrate/nitrite, and serum ischemia-modified albumin) were measured 6 hours postprocedure. In group SR, IR decreased antioxidant enzyme levels and increased oxidative metabolite levels (PD100 and D200 than in group SR (PD100 and D200 than in group SR (PD100 and D200 than in group SR (PD100 and D200 than in group SR (P<.01). Hepatic, renal, and lung nitrate/nitrite levels were lower in group D200 than in group SR (P<.05). Dexmedetomidine preserves the antioxidant enzyme levels and reduces toxic oxidant metabolites. Therefore, it can provide protection from oxidative injury caused by ionizing radiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Chronic studies in rats exposed to liquid effluent from coal gasification process.

    Science.gov (United States)

    Kostial, K; Blanusa, M; Rabar, I; Maljković, T; Kello, D; Landeka, M; Bunarević, A; Stara, J F

    1981-02-01

    The health effects of the E-effluent (water for quenching ash) from a coal gasification plant were assayed in a chronic experiment (16 month exposure) and a three generation reproduction study. Animals exposed to 100% E-effluent had an increased daily intake of various inorganic elements (Fe, Cu, K, I, Se, Cd, Hg, Pb, As, F and Cr). In spite of that, the exposed and control animals had the same mortality rate, haematological findings, urinary protein excretion, trace element concentrations in kidneys, liver and femur, bone composition and morphometry, and histological findings. The pre- and post-natal development and growth was unchanged during three generations. It is concluded that the higher intake of various inorganics caused no change in the parameters measured.

  11. Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development.

    Science.gov (United States)

    Thomas, Jennifer D; Tran, Tuan D

    2012-03-01

    Children exposed to alcohol prenatally suffer from a range of physical, neuropathological, and behavioral alterations, referred to as fetal alcohol spectrum disorders (FASD). Both the cerebellum and hippocampus are affected by alcohol exposure during development, which may contribute to behavioral and cognitive deficits observed in children with FASD. Despite the known neuropathology associated with prenatal alcohol exposure, many pregnant women continue to drink (heavy drinkers, in particular), creating a need to identify effective treatments for their children who are adversely affected by alcohol. We previously reported that choline supplementation can mitigate alcohol's effects on cognitive development, specifically on tasks which depend on the functional integrity of the hippocampus. The present study examined whether choline supplementation could differentially mitigate alcohol's effects on trace eyeblink classical conditioning (ECC, a hippocampal-dependent task) and delay ECC (a cerebellar-dependent task). Long-Evans rats were exposed to 5.25 g/kg/day alcohol via gastric intubation from postnatal days (PD) 4-9, a period of brain development equivalent to late gestation in humans. A sham-intubated control group was included. From PD 10-30, subjects received subcutaneous injections of 100 mg/kg choline chloride or vehicle. Beginning on PD 32-34, subjects were trained on either delay or trace eyeblink conditioning. Performance of subjects exposed to alcohol was significantly impaired on both tasks, as indicated by significant reductions in percentage and amplitude of conditioned eyeblink responses, an effect that was attenuated by choline supplementation on the trace, but not delay conditioning task. Indeed, alcohol-exposed subjects treated with choline performed at control levels on the trace eyeblink conditioning task. There were no significant main or interactive effects of sex. These data indicate that choline supplementation can significantly reduce the

  12. Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

    Science.gov (United States)

    Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

    2002-01-01

    During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

  13. The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form.

    Science.gov (United States)

    Halatek, Tadeusz; Stanislawska, Magdalena; Kaminska, Irena; Cieslak, Malgorzata; Swiercz, Radoslaw; Wasowicz, Wojciech

    2017-02-23

    Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m(3) of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity

  14. Genomic instability in quartz dust exposed rat lungs: Is inflammation responsible?

    Science.gov (United States)

    Albrecht, C.; Knaapen, A. M.; Cakmak Demircigil, G.; Coskun, Erdem; van Schooten, F. J.; Borm, P. J. A.; Schins, R. P. F.

    2009-02-01

    Exposure to quartz dusts has been associated with lung cancer and fibrosis. Although the responsible mechanisms are not completely understood, progressive inflammation with associated induction of persistent oxidative stress has been discussed as a key event for these diseases. Previously we have evaluated the kinetics of pulmonary inflammation in the rat model following a single intratracheal instillation of 2mg DQ12 quartz, either in its native form or upon its surface modification with polyvinylpyridine-N-oxide or aluminium lactate. This model has been applied now to evaluate the role of inflammation in the kinetics of induction of DNA damage and response at 3, 7, 28, and 90 days after treatment. Bronchoalveolar lavage (BAL) cell counts and differentials as well as BAL fluid myeloperoxidase activity were used as markers of inflammation. Whole lung homogenate was investigated to determine the induction of the oxidative and pre-mutagenic DNA lesion 8-hydroxy-2-deoxy-guanosine (8-OHdG) by HPLC/ECD, while mRNA and protein expression of oxidative stress and DNA damage response genes including hemeoxygenase-1 (HO-1) and apurinic/apyrimidinic endonuclease (APE/Ref-1) were evaluated using Western blotting and real time PCR. Isolated lung epithelial cells from the treated rats were used for DNA strand breakage analysis using the alkaline comet assay as well as for micronucleus scoring in May-Gruenwald-Giemsa stained cytospin preparations. In the rats that were treated with quartz, no increased 8-OHdG levels were observed, despite the presence of a marked and persistent inflammation. However, DNA strand breakage in the lung epithelial cells of the quartz treated rats was significantly enhanced at 3 days, but not at 28 days. Moreover, significantly enhanced micronucleus frequencies were observed for all four time points investigated. In the animals that were treated with the PVNO modified quartz, micronuclei scores did not differ from controls, while in those treated with

  15. Genomic instability in quartz dust exposed rat lungs: Is inflammation responsible?

    Energy Technology Data Exchange (ETDEWEB)

    Albrecht, C; Schins, R P F [Institut fuer Umweltmedizinische Forschung (IUF) at the Heinrich Heine University Duesseldorf (Germany); Demircigil, G Cakmak; Coskun, Erdem [Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara (Turkey); Schooten, F J van [Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Health Risk Analysis and Toxicology, University of Maastricht (Netherlands); Borm, P J A [Centre of Expertise in Life Sciences (Cel), Hogeschool Zuyd, Heerlen (Netherlands); Knaapen, A M, E-mail: catrin.albrecht@uni-duesseldorf.d

    2009-02-01

    Exposure to quartz dusts has been associated with lung cancer and fibrosis. Although the responsible mechanisms are not completely understood, progressive inflammation with associated induction of persistent oxidative stress has been discussed as a key event for these diseases. Previously we have evaluated the kinetics of pulmonary inflammation in the rat model following a single intratracheal instillation of 2mg DQ12 quartz, either in its native form or upon its surface modification with polyvinylpyridine-N-oxide or aluminium lactate. This model has been applied now to evaluate the role of inflammation in the kinetics of induction of DNA damage and response at 3, 7, 28, and 90 days after treatment. Bronchoalveolar lavage (BAL) cell counts and differentials as well as BAL fluid myeloperoxidase activity were used as markers of inflammation. Whole lung homogenate was investigated to determine the induction of the oxidative and pre-mutagenic DNA lesion 8-hydroxy-2-deoxy-guanosine (8-OHdG) by HPLC/ECD, while mRNA and protein expression of oxidative stress and DNA damage response genes including hemeoxygenase-1 (HO-1) and apurinic/apyrimidinic endonuclease (APE/Ref-1) were evaluated using Western blotting and real time PCR. Isolated lung epithelial cells from the treated rats were used for DNA strand breakage analysis using the alkaline comet assay as well as for micronucleus scoring in May-Gruenwald-Giemsa stained cytospin preparations. In the rats that were treated with quartz, no increased 8-OHdG levels were observed, despite the presence of a marked and persistent inflammation. However, DNA strand breakage in the lung epithelial cells of the quartz treated rats was significantly enhanced at 3 days, but not at 28 days. Moreover, significantly enhanced micronucleus frequencies were observed for all four time points investigated. In the animals that were treated with the PVNO modified quartz, micronuclei scores did not differ from controls, while in those treated with

  16. [Effect of Guilingji Capsule on the fertility, liver functions, and serum LDH of male SD rats exposed by 900 mhz cell phone].

    Science.gov (United States)

    Ma, Hui-Rong; Li, Yuan-Yuan; Luo, Ya-Ping; Ma, Xue-Lian; Gong, Zhi-Qiang

    2014-04-01

    To observe the effect of Guilingji Capsule (GC) on the fertility, liver functions, and serum lactate dehydrogenase (LDH) of adult male SD rats exposed by 900 MHz cell phone. Totally 18 adult male SD rats and 36 adult female rats in child-bearing period were selected and randomly divided into three groups according to weight equilibrium principle, i.e., the normal group, the radiated group, and the GC group, 6 males and 12 females in each group. Male rats in the normal group and all female rats were not radiated. Male rats in the radiated group and the GC group received radiation for 4 h per day, lasting for 18 successive days. Rats in the GC group received GC suspension at the daily dose of 0. 15 g/kg by gastrogavage at the same time. Equal volume of normal saline was administrated to other male rats. Then male rats were mated with corresponding female rats from the 14th radiation night to the 18th radiation night in the ratio of 1:2. Male rats were killed following on the next morning of ending the radiation. Female rats were normally fed and then killed before delivery. The pregnant outcomes of female rats in responding groups (the rates of pregnancy and the number of death fetus, birth weight, body length, and tail length) were observed and compared. Serum alanine aminotransferase (ALT), aspartate transferase (AST), AST/ALT, and LDH levels of the male rats were detected by colorimetry. Histological and morphological changes of liver were observed by HE staining. Compared with the normal group, the pregnancy rates of female rats decreased and the number of death fetus increased, the serum LDH level obviously increased in the radiated group (P LDH decreased in the GC group (P LDH level increased by exposure toy GSM 900 MHz cell phone. GC could prevent and treat the aforesaid lesion. But there was no statistical difference in serum ALT or AST levels.

  17. Biochemical enzyme activity in different tissues of rats exposed to a novel phosphorothionate (RPR-V).

    Science.gov (United States)

    Rahman, Mohammed F; Siddiqui, Mohammed K J

    2003-01-01

    The effects of a novel phosphorothionate (RPR-V) synthesized at Indian Institute of Chemical Technology, Hyderabad, was studied using three sub-chronic doses of 0.033 (low), 0.066 (medium) and 0.099 (high) mg kg(-1) in male and female rats for a period of 90 days. This long term and repeated treatment of RPR-V revealed that the membrane bound target enzymes Aspartate aminotransferase and Alanine aminotransferase increased significantly in serum and kidney, whereas these enzymes significantly decreased in liver and lung tissues when measured after 45 and 90 days of treatment. This compound also caused significant inhibition of RBC Acetylcholinesterase, target enzyme of organophosphorus compounds revealing its effect on normal synaptic transmission. Two way Anova studies disclosed that the alterations were mostly dose and time dependent, sexual dimorphism was not observed when the activities of male rats were compared with female rats. Enzyme recoveries were recorded after 28 days of post treatment, high degree positive correlation was observed with regard to these enzymes between serum versus kidney, whereas in case of serum versus liver and lung tissues high degree negative correlation was recorded. These enzyme profiles elucidates that they increased in serum but they decreased significantly in liver and lung indicating necrosis of these tissues. However, in case of kidney the level of these enzymes increased significantly with parallel to serum, which is suggestive of an increase synthesis of these enzymes, may be an adaptive mechanism due to the stress of the toxicant. These biomarker enzymes can be detected rapidly and hence may be used for the prediction and diagnosis of pesticide insults.

  18. Impaired Auditory and Contextual Fear Conditioning in Soman-Exposed Rats

    Science.gov (United States)

    2011-01-01

    around the electrodes and secured in place using dental acrylic. The incision sites were sutured and the rats were administered buprenorphine (10.5...and sarin induce a long-lasting naloxone-reversible analgesia in mice. Life Sci 1984;34:1415–22. Clement JG, Rosario S, Bessette E, Erhardt N. Soman and...Shih TM, Romano JA. The effects of choline on soman-induced analgesia and toxicity. Neurotoxicol Teratol 1988;10:287–94. Shih TM, Duniho SM, McDonough JH

  19. Influence of spironolactone after prenatal exposion on male fertility of the rat

    OpenAIRE

    Wittchen, Silke

    2010-01-01

    Tree groups of pregnant femal rats were formed: a control group and two groups treated with spironolactone (twice 20mg/kg BW at an eight-hour interval on the 10th or 15th day of gestation). The stage of development of the offspring was evaluated on the basis of the following criteria: individual body weight from the 1st to 21st day of life, time of eye opening, time of eruption of teeth, time of fur development and - with male offspring - time of decline of the testes. A change in postnata...

  20. Investigation of toxic factors affecting cells of rat brains exposed to 3-methylcatechol

    Directory of Open Access Journals (Sweden)

    George Emílio Sampaio Barreto

    2007-09-01

    Full Text Available The aim of this work was to study the effects of 3MC on the peroxidation of biomolecules in nuclear fractions and nonsynaptic mitochondrial respiration in organelles obtained from rat brains. The cytotoxicity towards rat primary astrocytes in vitro was also tested. 3MC at 1mM oxidized consuming oxygen at a rate of 1.98 ± 0.19 µM.min-1 and formed reactive quinones. At the same concentration, 3MC induced peroxidation of biomolecules in nuclear fractions obtained from rat brain homogenates and inhibited state 2 FADH2-linked respiration in nonsynaptic mitochondria. Furthermore, 3MC oxidized in the culture medium, leading to the formation of quinones. This toluene metabolite was cytotoxic to rat primary astrocytes. The concentration that killed 50% of cells after 72 h was 107 mM. The results of the study indicated a direct relationship between cytotoxicity and 3MC oxidation.O 3-metilcatecol (3MC é um metabólito do tolueno. Para esclarecer se o 3MC seria tóxico para o sistema nervoso central, examinou-se seus efeitos sobre a peroxidação de biomoléculas em frações nucleares e a respiração mitocondrial em organelas obtidas de cérebros de ratos. Também se testou a citotoxicidade para astrócitos primários de ratos. O 3MC a 1mM oxida-se consumindo oxigênio a uma taxa de 1,98 ± 0,19 mM.min-1, formando quinonas reativas. Nessa mesma concentração o 3MC peroxidou biomoléculas nas frações nucleares. Esse composto também inibiu o estado 2 da respiração mitocondrial associada ao FADH2. Além disso, o 3MC também se oxida em meio de cultura levando à formação de quinonas. Esse metabólito do tolueno foi citotóxico para astrócitos de ratos. A concentração que matou 50% das células após 72 horas foi 107 mM. Os resultados desse estudo indicam uma relação direta entre a citotoxicidade e a oxidação do 3MC.

  1. Isolation and identification of previtamin D/sub 3/ from the skin of rats exposed to ultraviolet irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Holick, M.F. (Massachusetts General Hospital, Boston); Richtand, N.M.; McNeill, S.C.; Holick, S.A.; Frommer, J.E.; Henley, J.W.; Potts, J.T. Jr.

    1979-03-20

    The process of the photolytic activation of vitamin D precursor(s) in the skin has been elucidated by a detailed analysis of the products formed after ultraviolet light exposure. The photolytic product isolated from the skin of rats exposed to ultraviolet irradiation was identified as previtamin D/sub 3/ by several criteria including its characteristic ultraviolet absorption spectrum, mass spectrum, and thermal isomerization to vitamin D/sub 3/, which itself was identified also by mass spectroscopy. Vitamin D/sub 3/ per se was not formed by ultraviolet irradiation-vitamin D/sub 3/ arises exclusively from the thermal conversion of previtamin D/sub 3/. Detectable amounts of lumisterol/sub 3/ or tachysterol/sub 3/ were not seen.

  2. Adaptive and non-adaptive responses in rats exposed to ozone, alone and in mixtures, with acidic aerosols.

    Science.gov (United States)

    Kleinman, M T; Mautz, W J; Bjarnason, S

    1999-03-01

    Healthy young adult (300 g) Sprague-Dawley rats were exposed for 1-day or 5-day periods, nose only, to purified air (CA) or four different pollutant atmospheres. Pollutant atmospheres included (a) 0.2 ppm ozone; (b) 0.4 ppm O3; (c) a low concentration mixture of ozone and sulfuric acid-coated carbon particles (0.2 ppm, 100 microg/m(3) and 50 microg/m(3), respectively); and (d) a high-concentration O3 and sulfuric acid-coated carbon particle mixture (0.4 ppm, 500 microg/m(3) and 250 microg/m(3), respectively). Following 1-day exposures to the high O3 concentration, significant (pmechanisms that have been reported by us and others after repeated exposures to ozone alone.

  3. Dendropanax morbifera Léveille extract facilitates cadmium excretion and prevents oxidative damage in the hippocampus by increasing antioxidant levels in cadmium-exposed rats

    OpenAIRE

    2014-01-01

    Background Dendropanax morbifera Léveille is used in herbal medicine as a cancer treatment. In this study, we investigated the effects of Dendropanax morbifera stem extract (DMS) on cadmium (Cd) excretion from the blood and kidney and brain tissues of rats exposed to cadmium, as well as the effects of DMS on oxidative stress and antioxidant levels in the hippocampus after Cd exposure. Methods Seven-week-old Sprague-Dawley rats were exposed to 2 mg/kg of cadmium by intragastric gavage and were...

  4. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    OpenAIRE

    Sílvia Regina de Lima Reis; Naoel Hassan Feres; Leticia Martins Ignacio-Souza; Roberto Vilela Veloso; Vanessa Cristina Arantes; Nair Honda Kawashita; Edson Moleta Colodel; Bárbara Laet Botosso; Marise Auxiliadora de Barros Reis; Márcia Queiroz Latorraca

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and ...

  5. Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells

    OpenAIRE

    Drel, Viktor R.; Pacher, Pal; Stevens, Martin J; Obrosova, Irina G.

    2006-01-01

    Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments, control (C) and streptozotocin-diabetic (D) rats were treated with...

  6. Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring.

    Science.gov (United States)

    Kim, Ki Chan; Lee, Dong-Keun; Go, Hyo Sang; Kim, Pitna; Choi, Chang Soon; Kim, Ji-Woon; Jeon, Se Jin; Song, Mi-Ryoung; Shin, Chan Young

    2014-02-01

    Imbalance in excitatory/inhibitory signal in the brain has been proposed as one of the main pathological features in autism spectrum disorders, although the underlying cellular and molecular mechanism is unclear yet. Because excitatory/inhibitory imbalance can be induced by aberration in glutamatergic/GABAergic neuronal differentiation, we investigated the mechanism of dysregulated neuronal differentiation between excitatory and inhibitory neurons in the embryonic and postnatal brain of prenatally valproic acid-exposed rat offspring, which is often used as an animal model of autism spectrum disorders. Transcription factor Pax6, implicated in glutamatergic neuronal differentiation, was transiently increased in embryonic cortex by valproate exposure, which resulted in the increased expression of glutamatergic proteins in postnatal brain of offspring. Chromatin immunoprecipitation showed increased acetylated histone binding on Pax6 promoter region, which may underlie the transcriptional up-regulation of Pax6. Other histone deacetylase (HDAC) inhibitors including TSA and SB but not valpromide, which is devoid of HDAC inhibitor activity, induced Pax6 up-regulation. Silencing Pax6 expression in cultured rat primary neural progenitor cells demonstrated that up-regulation of Pax6 plays an essential role in valproate-induced glutamatergic differentiation. Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a lesser extent with MPEP treatment, reversed the impaired social behaviors and seizure susceptibility of prenatally valproate-exposed offspring. Together, environmental factors may contribute to the imbalance in excitatory/inhibitory neuronal activity in autistic brain by altering expression of transcription factors governing glutamatergic/GABAergic differentiation during fetal neural development, in conjunction with the genetic preload.

  7. Site-specific changes in zinc levels in the epididymis of rats exposed to ionizing radiation

    Science.gov (United States)

    Homma-Takeda, S.; Nishimura, Y.; Watanabe, Y.; Yukawa, M.

    2007-07-01

    The epididymis is an accessory sex organ that plays an important role in sperm maturation and storage. Trace elements, such as copper (Cu), manganese (Mn), zinc (Zn) and selenium (Se), have a pivotal role in spermatogenesis. We studied the effects of radiation on trace element levels in the epididymis in male Wistar rats using inductively coupled plasma-mass spectrometry (ICP-MS). We determined trace element concentration in segment-dissected specimens and used micro-PIXE analysis to determine Zn in epididymal sections in situ. Zn concentrations in the caput and cauda epididymis of control rats were 37.7 ± 6.5 μg/g wet weight and 18.7 ± 4.1 μg/g wet weight, respectively. At 6 h after irradiation at a single dose of 5Gy, the Zn level decreased by 33% in the caput epididymis, whereas the level did not change in the cauda segment. Similar results were obtained for Se, but not both Cu and Mn. PIXE spot analysis revealed that Zn in the lumen of the epididymal tubules decreased after irradiation.

  8. Inflammation-like glial response in lead-exposed immature rat brain.

    Science.gov (United States)

    Struzynska, Lidia; Dabrowska-Bouta, Beata; Koza, Katarzyna; Sulkowski, Grzegorz

    2007-01-01

    Numerous studies on lead (Pb) neurotoxicity have indicated this metal to be a dangerous toxin, particularly during developmental stages of higher organisms. Astrocytes are responsible for sequestration of this metal in brain tissue. Activation of astroglia may often lead to loss of the buffering function and contribute to pathological processes. This phenomenon is accompanied by death of neuronal cells and may be connected with inflammatory events arising from the production of a wide range of cytokines and chemokines. The effects of prolonged exposure to Pb upon glial activation are examined in immature rats to investigate this potential proinflammatory effect. When analyzed at the protein level, glial activation is observed after Pb exposure, as reflected by the increased level of glial fibrillary acidic protein and S-100beta proteins in all parts of the brain examined. These changes are associated with elevation of proinflammatory cytokines. Production of interleukin (IL)-1beta and tumor necrosis factor-alpha is observed in hippocampus, and production of IL-6 is seen in forebrain. The expression of fractalkine is observed in both hippocampus and forebrain but inconsiderably in the cerebellum. In parallel with cytokine expression, signs of synaptic damage in hippocampus are seen after Pb exposure, as indicated by decreased levels of the axonal markers synapsin I and synaptophysin. Obtained results indicate chronic glial activation with coexisting inflammatory and neurodegenerative features as a new mechanism of Pb neurotoxicity in immature rat brain.

  9. The Alteration and Significance of Surfactant Protein A in Rats Chronically Exposed to Cigarette Smoke

    Institute of Scientific and Technical Information of China (English)

    Qiongjie HU; Huilan ZHANG; Shengdao XIONG; Xuemei SHI; Yongjian XU; Zhenxiang ZHANG; Guohua ZHEN; Jianping ZHAO

    2008-01-01

    In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was deter-mined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52±0.05) was lower than that of the N group (0.72±0.06) (P<0.05). The lev-els of mRNA of SPA in the lung tissues of the S group (0.3522±0.0512) was significantly lower than that of the N group (0.4432±0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host deense functions of surfactant in the peripheral airways, which might play a crucial role in the devel-opment of chronic obstructive lung disease.

  10. Comparable renovascular protective effects of moxonidine and simvastatin in rats exposed to cigarette smoke.

    Science.gov (United States)

    Nasr, Magda A; El-Gowilly, Sahar M; El-Mas, Mahmoud M

    2010-01-01

    Renovascular impairment plays a major role in smoking-induced nephrotoxicity. This study investigated the effect of the imidazoline I(1)-receptor/alpha(2)-adrenoceptor agonist moxonidine, as compared to the lipid lowering drug simvastatin, on abnormalities induced by cigarette smoke (CS) in renovascular reactivity. Six rat groups were used: control, CS (twice a day for 6weeks), simvastatin, moxonidine, CS+simvastatin, and CS+moxonidine. CS exposure increased plasma urea and creatinine and reduced plasma and renal nitrate/nitrite (NOx). In isolated perfused phenylephrine-preconstricted kidneys of CS rats, vasodilator responses to carbachol or isoprenaline, but not papaverine, were attenuated. Nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine (L-NNA) reduced carbachol vasodilations in control but not CS kidneys, suggesting the impairment of NOS activity by CS. Simultaneous administration of moxonidine or simvastatin abolished CS-induced abnormalities in indices of renal function, NOx, and vasodilations caused by carbachol or isoprenaline. The possibility whether alterations in antioxidant or lipid profiles contributed to the interaction was investigated. CS increased renal malondialdyde and decreased glutathione, and glutathione peroxidase, superoxide dismutase and catalase activities. Further, CS reduced plasma HDL and increased cholesterol, triglycerides, and LDL. Simvastatin or moxonidine abolished the deleterious CS effects on antioxidant activity; the lipid profile was normalized by simvastatin only. These findings highlight that renovascular dysfunction caused by CS and the underlying oxidative damage is evenly attenuated by moxonidine and simvastatin.

  11. Female rats exposed to stress and alcohol show impaired memory and increased depressive-like behaviors.

    Science.gov (United States)

    Gomez, J L; Luine, V N

    2014-01-17

    Exposure to daily life stressors is associated with increases in anxiety, depression, and overall negative affect. Alcohol or other psychoactive drugs are often used to alleviate stress effects. While females are more than twice as likely to develop mood disorders and are more susceptible to dependency than males, they are infrequently examined. In this study, female rats received no stress/no alcohol control (CON), alcohol alone (ALC), stress alone (STR), or stress plus alcohol (STR+ALC). Stress consisted of restraint for 6h/day/7days, and alcohol was administered immediately following restraint via gastric gavage at a dose of 2.0g/kg. Dependent measures included tests utilizing object recognition (OR), Y-maze, elevated plus maze (EPM), forced swim (FST), blood alcohol content, corticosterone levels, and body weights. ALC, STR+ALC, but not stress alone, impaired memory on OR. All treatments impaired spatial memory on the Y-maze. Anxiety was not affected on the EPM, but rats treated with alcohol or in combination with stress showed increased immobility on the FST, suggestive of alcohol-induced depression. Previously, we found alcohol reversed deleterious effects of stress on memory and mood in males, but current results show that females reacted negatively when the two treatments were combined. Thus, responses to alcohol, stress and their combination suggest that sex specific treatments are needed for stress-induced behavioral changes and that self-medicating with alcohol to cope with stress maybe deleterious in females.

  12. Neuronal reorganization in adult rats neonatally exposed to (±-3,4-methylenedioxymethamphetamine

    Directory of Open Access Journals (Sweden)

    Michael T. Williams

    2014-01-01

    Full Text Available The abuse of methylenedioxymethamphetamine (MDMA during pregnancy is of concern. MDMA treatment of rats during a period of brain growth analogous to late human gestation leads to neurochemical and behavioral changes. MDMA from postnatal day (P11–20 in rats produces reductions in serotonin and deficits in spatial and route-based navigation. In this experiment we examined the impact of MDMA from P11 to P20 (20 mg/kg twice daily, 8 h apart on neuronal architecture. Golgi impregnated sections showed significant changes. In the nucleus accumbens, the dendrites were shorter with fewer spines, whereas in the dentate gyrus the dendritic length was decreased but with more spines, and for the entorhinal cortex, reductions in basilar and apical dendritic lengths in MDMA animals compared with saline animals were seen. The data show that neuronal cytoarchitectural changes are long-lasting following developmental MDMA exposure and are in regions consistent with the learning and memory deficits observed in such animals.

  13. Prenatal effects by exposing to amoxicillin on dental enamel in Wistar rats.

    Science.gov (United States)

    Gottberg, Beatriz; Berné, Jeanily; Quiñónez, Belkis; Solórzano, Eduvigis

    2014-01-01

    Amoxicillin is an antibiotic widely prescribed; its most frequent side effects are gastrointestinal disorders and hypersensitivity reactions. Over the last 10 years studies have been published which suggest that amoxicillin may cause dental alterations similar to dental fluorosis. Never the less, the results are not conclusive, this is why it was planned the need to make controlled studies on test animals. The purpose of this study was to determine the effect produced by amoxicillin prenatal administration on dental enamel in Wistar rats. 12 pregnant adult rats were used distributed into five different groups: witness control (n=2) didn't get any treatment; negative control (n=2) they were prescribed with saline solution; positive control (n=3) they were prescribed with tetracycline 130 mg/kg, and two groups (n=3 and n=2) treated with amoxicillin doses of 50 and 100 mg/kg respectively. The treatments were daily administered by mouth, from the 6th gestation day to the end of gestation. Twenty five days after they were born, the offspring were sacrificed with a sodium pentobarbital overdose, the mandible was dissected and the first lower molars were gotten. The samples were fixed in 10% formaldehyde solution and clinically and histologically observed to determine any enamel disorders. hypomineralization was observed in every single sample of the tetracyclic and amoxicillin treated group 100 mg/kg, meanwhile only 50% from the group administered with 50 mg/kg amoxicillin showed this histological disorder. the side effect caused by amoxicillin on dental enamel was doses dependent.

  14. Hepatotoxicity and nephrotoxicity evaluation in Wistar albino rats exposed to Morinda lucida leaf extract

    Directory of Open Access Journals (Sweden)

    Taofeeq Oduola

    2010-05-01

    Full Text Available Background: Aqueous extract of Morinda lucida benth leaf is consumed in Southern Nigeria in the treatment of malaria without any regard for its safety. Aim: The aim of the study was to investigate the effects of ingestion of the ethanolic leaf extract of the plant on liver and kidney functions in Wistar albino rats. Materials and Methods: Acute oral toxicity test was performed to determine the LD50; sub-chronic toxicity study was then carried out by oral administration of different doses of the extract on daily basis to different groups of rats for 42 days. The animals were subsequently sacrificed, and liver and kidney functions assessed biochemically using standard techniques. Results: The acute oral toxicity result, LD50, revealed Morinda lucida leaf extract to be non-lethal at 6400mg/kg body weight. The results obtained for liver and kidney function parameters indicated that ingestion of Morinda lucida leaf extract has no toxic effect on liver and kidney functions. Conclusion: The results can form the basis for clinical trials in humans.

  15. Hepatotoxicity and nephrotoxicity evaluation in Wistar albino rats exposed to Morinda lucida leaf extract

    Directory of Open Access Journals (Sweden)

    Taofeeq Oduola

    2010-01-01

    Full Text Available Background: Aqueous extract of Morinda lucida benth leaf is consumed in Southern Nigeria in the treatment of malaria without any regard for its safety. Aim: The aim of the study was to investigate the effects of ingestion of the ethanolic leaf extract of the plant on liver and kidney functions in Wistar albino rats. Materials and Methods: Acute oral toxicity test was performed to determine the LD 50 ; sub-chronic toxicity study was then carried out by oral administration of different doses of the extract on daily basis to different groups of rats for 42 days. The animals were subsequently sacrificed, and liver and kidney functions assessed biochemically using standard techniques. Results: The acute oral toxicity result, LD 50, revealed Morinda lucida leaf extract to be non-lethal at 6400mg/kg body weight. The results obtained for liver and kidney function parameters indicated that ingestion of Morinda lucida leaf extract has no toxic effect on liver and kidney functions. Conclusion: The results can form the basis for clinical trials in humans.

  16. Site-specific changes in zinc levels in the epididymis of rats exposed to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Homma-Takeda, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan)]. E-mail: shino_ht@nirs.go.jp; Nishimura, Y. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan); Watanabe, Y. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan); Yukawa, M. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan)

    2007-07-15

    The epididymis is an accessory sex organ that plays an important role in sperm maturation and storage. Trace elements, such as copper (Cu), manganese (Mn), zinc (Zn) and selenium (Se), have a pivotal role in spermatogenesis. We studied the effects of radiation on trace element levels in the epididymis in male Wistar rats using inductively coupled plasma-mass spectrometry (ICP-MS). We determined trace element concentration in segment-dissected specimens and used micro-PIXE analysis to determine Zn in epididymal sections in situ. Zn concentrations in the caput and cauda epididymis of control rats were 37.7 {+-} 6.5 {mu}g/g wet weight and 18.7 {+-} 4.1 {mu}g/g wet weight, respectively. At 6 h after irradiation at a single dose of 5Gy, the Zn level decreased by 33% in the caput epididymis, whereas the level did not change in the cauda segment. Similar results were obtained for Se, but not both Cu and Mn. PIXE spot analysis revealed that Zn in the lumen of the epididymal tubules decreased after irradiation.

  17. Alteration of protein profile in rat liver of animals exposed to subacute diazinon: a proteomic approach.

    Science.gov (United States)

    Lari, Parisa; Rashedinia, Marzieh; Abnous, Khalil; Hosseinzadeh, Hossein

    2014-05-01

    Diazinon, an organophosphorus insecticide, is employed to control pests in agriculture. Diazinon may contaminate the environment during the manufacturing process or agricultural application. Previous studies have revealed that diazinon may induce alteration in the protein profile of the liver. Here, a proteomics approach was used to investigate the effects on the protein profile in the liver of rats of subacute oral exposures at 15 mg/kg of diazinon. Liver proteins were separated using 2D-PAGE, and stained by MS-compatible silver staining and/or the fluorescent SYPRO® Ruby protein gel stain. Gels were scanned and analyzed using the Image Master software. Differentially displayed protein species were identified using MALDI-TOF/TOF and MASCOT software. Significantly altered protein species were identified to be involved in apoptosis, cell metabolism, transport, and antioxidant systems. Exposure to diazinon decreased levels of some species of catalase, peroxiredoxin-6, 3-ketoacyl-CoA thiolase, and glucose regulated protein78, whereas the level of protein disulfide-isomerase A3 increased. Our results suggested that diazinon may induce hepatotoxicity through oxidative stress, apoptosis, and metabolic disorders in rat liver.

  18. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation

    Science.gov (United States)

    Bendre, M; Comasco, E; Nylander, I; Nilsson, K W

    2015-01-01

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption affect Maoa expression in stress- and reward-related brain regions in the rat. Outbred Wistar rats were exposed to rearing conditions associated with stress (prolonged maternal separation) or no stress during early life, and given free choice between alcohol and/or water in adulthood. Transcript levels of Maoa were assessed in the ventral tegmental area, nucleus accumbens (NAc), medial prefrontal cortex, cingulate cortex, amygdala and dorsal striatum (DS). Blood was collected to assess corticosterone levels. After alcohol consumption, lower blood corticosterone and Maoa expression in the NAc and DS were found in rats exposed to early life stress compared with control rats. An interaction between early life stress and voluntary alcohol intake was found in the NAc. Alcohol intake before death correlated negatively with Maoa expression in DS in high alcohol-drinking rats exposed to early life stress. Maoa expression is sensitive to adulthood voluntary alcohol consumption in the presence of early life stress in outbred rats. These findings add knowledge of the molecular basis of the previously reported associations between early life stress, MAOA and susceptibility to alcohol misuse. PMID:26645625

  19. Cooperative Atlantic States Shark Pupping and Nursery (COASTSPAN)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Survey of inshore areas used by sharks for pupping and nurseries. Various locations have been surveyed, from the U.S. Virgin Islands to Massachusetts, most in...

  20. Northern fur seal pup weights, Pribilof Islands, Alaska, 1957-present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This database contains northern fur seal pup mass and length data by date, island, rookery and sex on the Pribilof Islands, Alaska, collected between 1957-2012. Mass...

  1. Mouse Gives Birth to Pups Using 3-D Printed Ovary

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_165622.html Mouse Gives Birth to Pups Using 3-D Printed Ovary Breakthrough ... to use hormone replacement therapies in order to trigger puberty," explained co-researcher Monica Laronda. She's a ...

  2. Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

    Directory of Open Access Journals (Sweden)

    Cabrera R.J.

    1999-01-01

    suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can induce long-lasting changes in the neurotransmitter systems involved in emotional regulation. Further experiments using neurochemical and pharmacological approaches would be interesting in this model.

  3. Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2005-01-01

    Membrane-bound enzymes play a vital role in neuronal function through maintenance of membrane potential and impulse propagation. We have evaluated the harmful effects of chronic cigarette smoking on membrane-bound ATPases and the protective effect of Bacoside A in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with Bacoside A (the active principle isolated from Bacopa monniera) at a dosage of 10 mg/kg b.w/day, p.o. The levels of lipid peroxides as marker for evaluating the extent of membrane damage, the activities of Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase, and associated cations sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) were investigated in the brain. Neuronal membrane damage was evident from the elevated levels of lipid peroxides and decreased activities of membrane-bound enzymes. Disturbances in the electrolyte balance with accumulation of Na+ and Ca2+ and depletion of K+ and Mg2+ were also observed. Administration of Bacoside A inhibited lipid peroxidation, improved the activities of ATPases, and maintained the ionic equilibrium. The results of our study indicate that Bacoside A protects the brain from cigarette smoking induced membrane damage.

  4. Postnatal Administration of Allopregnanolone Modifies Glutamate Release but Not BDNF Content in Striatum Samples of Rats Prenatally Exposed to Ethanol

    Directory of Open Access Journals (Sweden)

    Roberto Yunes

    2015-01-01

    Full Text Available Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c. administered to juvenile male rats (day 21 of age on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8. Prenatal ethanol administration decreased the K+-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.

  5. Testosterone has antidepressant-like efficacy and facilitates imipramine-induced neuroplasticity in male rats exposed to chronic unpredictable stress.

    Science.gov (United States)

    Wainwright, Steven R; Workman, Joanna L; Tehrani, Amir; Hamson, Dwayne K; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-03-01

    Hypogonadal men are more likely to develop depression, while testosterone supplementation shows antidepressant-like effects in hypogonadal men and facilitates antidepressant efficacy. Depression is associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and testosterone exerts suppressive effects on the HPA axis. The hippocampus also plays a role in the feedback regulation of the HPA axis, and depressed patients show reduced hippocampal neuroplasticity. We assessed the antidepressant-like effects of testosterone with, or without, imipramine on behavioral and neural endophenotypes of depression in a chronic unpredictable stress (CUS) model of depression. A 21-day CUS protocol was used on gonadectomized male Sprague-Dawley rats treated with vehicle, 1mg of testosterone propionate, 10mg/kg of imipramine, or testosterone and imipramine in tandem. Testosterone treatment reduced novelty-induced hypophagia following CUS exposure, but not under non-stress conditions, representing state-dependent effects. Further, testosterone increased the latency to immobility in the forced swim test (FST), reduced basal corticosterone, and reduced adrenal mass in CUS-exposed rats. Testosterone also facilitated the effects of imipramine by reducing the latency to immobility in the FST and increasing sucrose preference. Testosterone treatment had no significant effect on neurogenesis, though the combination of testosterone and imipramine increased PSA-NCAM expression in the ventral dentate gyrus. These findings demonstrate the antidepressant- and anxiolytic-like effects of testosterone within a CUS model of depression, and provide insight into the mechanism of action, which appears to be independent of enhanced hippocampal neurogenesis.

  6. Examination of the effects of varenicline, bupropion, lorcaserin, or naltrexone on responding for conditioned reinforcement in nicotine-exposed rats.

    Science.gov (United States)

    Guy, Elizabeth G; Fisher, Daniel C; Higgins, Guy A; Fletcher, Paul J

    2014-12-01

    Smoking tobacco remains one of the leading causes of preventable deaths in North America. Nicotine reinforces smoking behavior, in part, by enhancing the reinforcing properties of reward-related stimuli, or conditioned stimuli (CSs), associated with tobacco intake. To investigate how pharmaceutical interventions may affect this property of nicotine, we examined the effect of four US Food and Drug Administration (FDA) approved drugs on the ability of nicotine to enhance operant responding for a CS as a conditioned reinforcer. Thirsty rats were exposed to 13 Pavlovian sessions where a CS was paired with water delivery. Nicotine (0.4 mg/kg) injections were administered before each Pavlovian session. Then, in separate groups of rats, the effects of varenicline (1 mg/kg), bupropion (10 and 30 mg/kg), lorcaserin (0.6 mg/kg), and naltrexone (2 mg/kg), and their interaction with nicotine on responding for conditioned reinforcement were examined. Varenicline and lorcaserin each reduced nicotine-enhanced responding for conditioned reinforcement, whereas naltrexone had a modest effect of reducing response enhancements by nicotine. In contrast, bupropion enhanced the effect of nicotine on this measure. The results of these studies may inform how pharmaceutical interventions can affect smoking cessation attempts and relapse through diverse mechanisms, either substituting for, or interacting with, the reinforcement-enhancing properties of nicotine.

  7. Vascular Imaging of Solid Tumors in Rats with a Radioactive Arsenic-Labeled Antibody that Binds Exposed Phosphatidylserine

    Science.gov (United States)

    Jennewein, Marc; Lewis, Matthew A.; Zhao, Dawen; Tsyganov, Edward; Slavine, Nikolai; He, Jin; Watkins, Linda; Kodibagkar, Vikram D.; O'Kelly, Sean; Kulkarni, Padmakar; Antich, Peter P.; Hermanne, Alex; Roösch, Frank; Mason, Ralph P.; Thorpe, Philip E.

    2012-01-01

    Purpose We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. Experimental Design Bavituximab was labeled with 74As (β+,T1/2 17.8 days) or 77As (β−,T1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats. Results Clear images of the tumors were obtained using planar γ-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium. Conclusions These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors. PMID:18316558

  8. Biological Activities of QIAPI 1 as a Melanin Precursor and Its Therapeutic Effects in Wistar Rats Exposed to Arsenic Poisoning.

    Science.gov (United States)

    Solís-Herrera, Arturo; Ashraf, Ghulam M; del C A Esparza, María; Arias, Ruth I S; Bachurin, Sergei O; Barreto, George E; Aliev, Gjumrakch

    2015-01-01

    The chemical process initiated by QIAPI 1 has been deemed to be the most important biological reaction associated with human photosynthesis, and possibly neuroprotective effects under various inflammatory events. However, the detailed biological activities of QIAPI 1 as a melanin precursor are still unknown. In the present work, cytotoxicity test was done by MTT assay to determine cell viability of various cell lines (WI-38, A549, HS 683) like proliferation tests and its effect on cytokine production. Arsenic poisoning is an often-unrecognized cause of renal insufficiency. No prophylactic and/or therapeutic compounds have shown promising results against kidney diseases. The pathogenesis of Arsenic-induced nephropathy is not clear. Arsenic, as itself, does not degrade over time in the environment, and its accumulation may induce toxic effects. In this study, we also report the histological findings of the kidney in 3 groups of Wistar rats, a control group, a group exposed to arsenic in the water; and a group exposed to arsenic and treated with QIAPI 1 simultaneously. The findings of the current evidence indicates a potential therapeutic ability of QIAPI 1.

  9. Long-term spatial memory and morphological changes in hippocampus of Wistar rats exposed to smoke from Carica papaya leaves

    Institute of Scientific and Technical Information of China (English)

    Aboyeji Lukuman Oyewole; Bamidele Victor Owoyele

    2014-01-01

    Objective:To investigate the effects of smoking of dried leaves of Carica papaya (pawpaw) based on ethnopharmacological information which indicated that smoking of papaya leaves could influence motor performance and learning. Methods:Twenty-four rats were used for the study, and were grouped into four groups. Groups 1 served as the control (not exposed to papaya leaves smoke), while Groups 2, 3 and 4 were exposed to smoke from 6.25 g, 12.50 g and 18.75 g of dry pawpaw leaves respectively in a smoking chamber twice daily for 21 d with each exposure lasting for 3 min. Lastly, hippocampus was harvested in each group for histological study. Results: The results showed that there were significant (P Conclusions: In conclusion, the findings from this study has demonstrated that smoking of papaya leaves has the ability to maintain an intact long-term spatial memory at all doses but retrieving such memory is faster with the low and medium dosages.

  10. Effects of SO2 derivatives on sodium currents in acutely isolated rat hippocampal lead-exposed neurons

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this study, the effects of acute SO2 derivatives and chronic lead exposure together on sodium cur-rents (INa) were investigated in acutely isolated rat hippocampal neurons by using the whole-cell patch clamp techniques. We found that chronic lead exposure hardly reduced the amplitudes of INa. In the normal condition, sodium current started to appear at around ?70 mV, and reached the peak current at around ?40 mV. After chronic lead exposure, the data changed to ?70 and ?30 mV. After adding SO2 derivatives, the data changed to ?80 and ?40 mV, respectively. SO2 derivatives caused a significant in-crease of INa in hippocampal chronic-lead exposed neurons. Chronic lead exposure induced a right shift of the activation curve and a left shift of the inactivation curve of sodium channels. SO2 derivatives caused negative shifts of the activation and inactivation curves of INa in hippocampal chronic-lead ex-posed neurons. Lead exposure put off the time reaching the peak of INa activation. SO2 derivatives in-creased the time constants of inactivation after lead exposure. The interaction of lead and SO2 deriva-tives with voltage-dependent sodium channels may lead to changes in electrical activity and contribute to worsening the neurotoxicological damage.

  11. The rabbit pup, a natural model of nursing anticipatory activity

    OpenAIRE

    Caba, Mario; González-Mariscal, Gabriela

    2009-01-01

    Mother rabbits nurse their young once a day with circadian periodicity. Nursing bouts are brief (ca. 3 min) and occur inside the maternal burrow. Despite this limited contact mother rabbits and their pups are tuned to each other to ensure that the capacities of each party are used efficiently to ensure the weaning of a healthy litter. In this review we present behavioral, hormonal, metabolic and hormonal correlates of this phenomenon in mother rabbits and their pups. Research is revealing tha...

  12. Hepatic miRNA profiles and thyroid hormone homeostasis in rats exposed to dietary potassium perfluorooctanesulfonate (PFOS).

    Science.gov (United States)

    Dong, Hongyan; Curran, Ivan; Williams, Andrew; Bondy, Genevieve; Yauk, Carole L; Wade, Michael G

    2016-01-01

    Perfluorooctanesulfonate (PFOS) has been widely used in a variety of industrial and commercial applications as a surfactant and stain repellent. PFOS causes liver damage (including liver tumors) in experimental animals, primarily via interaction with PPARα and CAR/PXR. We investigated the involvement of microRNAs (miRNAs) in PFOS-induced hepatotoxicity, and mechanisms involved in abnormal thyroid hormone (TH) homeostasis, in the livers of adult male rats exposed in feed to 50mg PFOS/kg diet for 28 days. PFOS-treated rats exhibited expected histopathological and clinical chemistry changes, and global gene expression changes consistent with the involvement of PPARα and CAR/PXR. Thirty-eight miRNAs were significantly altered. Three members of the miR-200 family were the most increased, while miR-122-5p and miR-21-5p were the most decreased, in PFOS-treated rats. Expression of the miR-23b-3p/27b-3p/24-3p cluster also decreased in PFOS-treated animals. Pathway analysis of miRNAs and associated gene expression changes suggests involvement of epithelial to mesenchymal transition (EMT), which is a primary process of tumor cell motility and cancer metastasis. Our analysis also revealed transcripts that may mediate PFOS-induced effects on TH homeostasis including: activation of the CAR/PXR pathway, phase II/III enzymes, and deiodinase. These changes are consistent with low serum TH due to enhanced metabolic clearance of TH. However, most TH hepatic target genes were not altered in a manner consistent with reduced TH signaling, suggesting that PFOS exposure did not induce functional hypothyroidism. Collectively, the study suggests an important role for miRNAs in PFOS-induced hepatotoxicity and provides insight into the effects of PFOS on TH homeostasis.

  13. Systemic Th17/IL-17A response appears prior to hippocampal neurodegeneration in rats exposed to low doses of ozone.

    Science.gov (United States)

    Solleiro-Villavicencio, H; Rivas-Arancibia, S

    2017-06-03

    Exposure to low doses of O3 leads to a state of oxidative stress. Some studies show that oxidative stress can modulate both the CNS and systemic inflammation, which are important factors in the development of Alzheimer disease (AD). This study aims to evaluate changes in the frequency of Th17-like cells (CD3(+)CD4(+)IL-17A(+)), the concentration of IL-17A in peripheral blood, and hippocampal immunoreactivity to IL-17A in rats exposed to low doses of O3. One hundred eight male Wistar rats were randomly assigned to 6 groups (n=18) receiving the following treatments: control (O3 free) or O3 exposure (0.25ppm, 4hours daily) over 7, 15, 30, 60, and 90 days. Twelve animals from each group were decapitated and a peripheral blood sample was taken to isolate plasma and mononuclear cells. Plasma IL-17A was quantified using LUMINEX, while Th17-like cells were counted using flow cytometry. The remaining 6 rats were deeply anaesthetised and underwent transcardial perfusion for immunohistological study of the hippocampus. Results show that exposure to O3 over 7 days resulted in a significant increase in the frequency of Th17-like cells and levels of IL-17A in peripheral blood. However, levels of Th17/IL-17A in peripheral blood were lower at day 15 of exposure. We also observed increased IL-17A in the hippocampus beginning at 30 days of exposure. These results indicate that O3 induces a short-term, systemic Th17-like/IL-17A effect and an increase of IL-17A in the hippocampal tissue during the chronic neurodegenerative process. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Role of Acorus calamus and alpha-asarone on hippocampal dependent memory in noise stress exposed rats.

    Science.gov (United States)

    Sundaramahalingam, Manikandan; Ramasundaram, Srikumar; Rathinasamy, Sheela Devi; Natarajan, Ruvanthika Pulipakkam; Somasundaram, Thangam

    2013-08-15

    Stress is a condition or stimulus that threatens an organism's survival. Noise is an environmental stressor. It is well known that long term as well as acute exposure to noise led to oxidative stress. In the present study, it was investigated that the persistence of noise stress (100 dBA/4 h/d for 30 days) could cause memory impairment in rats and whether ethylacetate extract of AC EAAC (50 mg kg(-1) b.wt.) and alpha-Asarone (9 mg kg(-1) b.wt.). treatment can prevent or not. In order to understand the possible mechanism behind it, antioxidant status and acetylcholinesterase (AChE) activity in hippocampus was evaluated after rats were tested in Radial Eight-arm Maze (RAM). Heat shock protein 70 (hsp 70) expression in hippocampus was also evaluated to understand the intensity of stress level. Results showed that after noise stress exposure, time taken to visit all the baited arms, working and reference memory errors were increased in RAM. The superoxide dismutase, lipid peroxidation, AChE activity, hsp 70 were significantly increased with concomitant decrease in catalase, glutathione peroxidase activity and G6PD activity of non-enzymatic levels was observed in the 30 days noise stress exposed group. When rats were co-administrated with EAAC and alpha-Asarone prevents the noise stress induced alterations significantly. In Conclusion, noise stress induced oxidative stress, increased AChE activity, and over expression of hsp 70 in hippocampus region might have led to the impairment of spatial memory. EAAC and alpha-Asarone prevents this noise stress induced memory impairment.

  15. Effect of vitamins A, E and C on liver enzyme activity in rats exposed to organophosphate pesticide diazinon.

    Science.gov (United States)

    Shokrzadeh, Mohammad; Shobi, Sepideh; Attar, Hossein; Shayegan, Sahel; Payam, Sakineh Sadat Hosseini; Ghorbani, Faezeh

    2012-10-01

    Diazinon, a commonly used organophosphorus pesticide, has been widely used throughout the world in agriculture and horticulture to control insects that feed on crops, ornamentals, lawns, fruits, vegetables and other food products. The toxicity of the DZN causes adverse effects on many organs. The purpose of this study was to examine the protective effect of vitamins A, E and C on liver enzymes alanine transaminase (ALT), Aspartate aminotransferase (AST) and Lactate Dehydrogenase (LDH) in rats exposed to diazinon. In this study, male wistar rats were randomly divided into 10 different groups. The groups were administered normal saline, soybean oil (as the solvent for diazinon and fat-soluble vitamins), diazinon, (30 mg kg(-1), vitamins E, C and A (100, 500 mg kg(-1) and 400 IU kg(-1), respectively) and a combination of diazinon with the same dose of each vitamin intraperitoneally i.p.daily for 14 days. Seven days after the final injection, the animals were anesthetized and blood samples were taken. The photometric method was used to measure the activity of the enzymes. The activities of ALT and AST in the diazinon group were significantly higher than that observed in the control group; however, the diazinon/vitamin E, A, C group displayed significant reduction in ALT and AST activities compared to the diazinon group. The lowest level of LDH enzyme activity was observed in the dazinon/vitamin C group and this was statistically lower than the diazinon group. The results of this study revealed that vitamin E, A and C have a potent protective effect against diazinon-induced hepatotoxicity in rats, which may be due to the scavenging of free radicals and increased antioxidant status.

  16. Sensory feedback alters spontaneous limb movements in newborn rats: effects of unilateral forelimb weighting.

    Science.gov (United States)

    Brumley, Michele R; Robinson, Scott R

    2013-05-01

    Perinatal mammals show spontaneous movements that often appear random and uncoordinated. Here, we examined if spontaneous limb movements are responsive to a proprioceptive manipulation by applying a weight unilaterally to a forelimb of postnatal day 0 (P0; day of birth) and P1 rats. Weights were calibrated to approximate 0%, 25%, 50%, or 100% of the average mass of a forelimb, and were attached at the wrist. P0 and P1 pups showed different levels of activity during the period of limb weighting, in response to weight removal, and during the period after weighting. Pups exposed to 50% and 100% weights showed proportionately more activity in the nonweighted forelimb during the period of weighting, suggesting a threshold for evoking proprioceptive changes. Findings suggest that newborn rats use movement-related feedback to modulate spontaneous motor activity, and corroborate studies of human infants that have suggested a role for proprioception during early motor development.

  17. Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats

    Science.gov (United States)

    Coleman, Jamison; Williams, Ashley; Phan, Tam-Hao T.; Mummalaneni, Shobha; Melone, Pamela; Ren, ZuoJun; Zhou, Huiping; Mahavadi, Sunila; Murthy, Karnam S.; Katsumata, Tadayoshi; DeSimone, John A.

    2011-01-01

    Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5–40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure. PMID:21849614

  18. Sex-Specific Metabolic Outcomes in Offspring of Female Rats Born Small or Exposed to Stress During Pregnancy.

    Science.gov (United States)

    Cheong, Jean N; Cuffe, James S M; Jefferies, Andrew J; Anevska, Kristina; Moritz, Karen M; Wlodek, Mary E

    2016-11-01

    Low birth weight increases adult metabolic disease risk in both the first (F1) and second (F2) generation. Physiological stress during pregnancy in F1 females that were born small induces F2 fetal growth restriction, but the long-term metabolic health of these F2 offspring is unknown. Uteroplacental insufficiency (restricted) or sham (control) surgery was performed in F0 rats. F1 females (control, restricted) were allocated to unstressed or stressed pregnancies. F2 offspring exposed to maternal stress in utero had reduced birth weight. At 6 months, F2 stressed males had elevated fasting glucose. In contrast, F2 restricted males had reduced pancreatic β-cell mass. Interestingly, these metabolic deficits were not present at 12 month. F2 males had increased adrenal mRNA expression of steroidogenic acute regulatory protein and IGF-1 receptor when their mothers were born small or exposed to stress during pregnancy. Stressed control F2 males had increased expression of adrenal genes that regulate androgen signaling at 6 months, whereas expression increased in restricted male and female offspring at 12 months. F2 females from stressed mothers had lower area under the glucose curve during glucose tolerance testing at 12 months compared with unstressed females but were otherwise unaffected. If F1 mothers were either born small or exposed to stress during her pregnancy, F2 offspring had impaired physiological outcomes in a sex- and age-specific manner. Importantly, stress during pregnancy did not exacerbate disease risk in F2 offspring of mothers born small, suggesting that they independently program disease in offspring through different mechanisms.

  19. Weights, growth, and survival of timber wolf pups in Minnesota

    Science.gov (United States)

    Van Ballenberghe, V.; Mech, L.D.

    1975-01-01

    Weights, growth rates, canine tooth lengths, and survival data were obtained from 73 wild wolf (Canis lupus) pups that were 8 to 28 weeks old when live-trapped in three areas of northern Minnesota from 1969 to 1972. Relative weights of wild pups are expressed as percentages of a standard weight curve based on data from captive pups of similar age. These relative weights varied greatly within litters, between litters, and between years; extremes of 31 to 144 percent of the standard were observed. Growth rates ranging from 0.05 to 0.23 kilograms per day were observed, and similar variations in general devel pment and in replacement and growth of canine teeth were noted. Survival data based on radio-tracking and tag returns indicated that pups with relative weights less than 65 percent of standard have a poor chance of survival, whereas pups of at least 80 percent of standard weight have a high survivability. Pups born in 1972 were especially underweight, probably a result of declining white-tailed deer (Odocoileus virginianus) densities in the interior of the Superior National Forest study area.

  20. The effects of in vitro exposure to white spirit on [Ca2+] in synaptosomes from rats exposed prenatally to white spirit

    DEFF Research Database (Denmark)

    Edelfors, S.; Hass, Ulla; Ravn-Jonsen, A.

    1999-01-01

    in all groups of rats. The membrane leakage measured as FURA-2 leakage from the synaptosomes identical in all three groups of animals. The results suggest that prenatal exposure to white spirit induces long-lasting and possibly irreversible changes in calcium homeostasis in the rat nervous system.......Female rats were exposed to white spirit (400 and 800 ppm for 6 hr/day) at day 7-20 during pregnancy. Thirty-five days after birth all female offspring were sacrificed, the brains removed, and the synaptosomal fractions prepared for in vitro studies. The cytosolic calcium concentration was measured...

  1. Temporal Development of Gut Microbiota in Triclocarban Exposed Pregnant and Neonatal Rats

    Science.gov (United States)

    Kennedy, Rebekah C.; Fling, Russell R.; Robeson, Michael S.; Saxton, Arnold M.; Donnell, Robert L.; Darcy, John L.; Bemis, David A.; Liu, Jiang; Zhao, Ling; Chen, Jiangang

    2016-01-01

    Alteration of gut microbial colonization process may influence susceptibility of the newborn/infant to infectious and chronic disease. Infectious disease risk leads to widespread use of non-prescription antimicrobials in household products such as Triclocarban (TCC), an antimicrobial compound in personal care products. TCC concentrates in and is transferred through the milk to suckling offspring. TCC exposure during gestation and lactation significantly reduced phylogenetic diversity (PD) among exposed dams and neonates. Among dams using weighted UniFrac distances, TCC induced significant dysbiosis of gut microbiota by gestational day (GD) 18, a trend that continued after delivery. Similarly, an overall restructuring of gut microbiota occurred in neonates. By postnatal day (PND) 12, communities separated based on exposure status and became significantly different at PND 16. The ability of TCC to drive microbial dysbiosis warrants future investigation to evaluate the safety of non-prescription antimicrobial use, including TCC, during critical exposure windows. PMID:27646684

  2. Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams

    Science.gov (United States)

    Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.

  3. Effects of Methimepip and JNJ-5207852 in Wistar rats exposed to an open-field with and without object and in Balb/c mice exposed to an open-space spatial maze

    Directory of Open Access Journals (Sweden)

    Abdel eEnnaceur

    2012-07-01

    Full Text Available The role of the histamine H3 receptor in anxiety is controversial, due to limitations in drug selectivity and limited validity of behavioral tests in previous studies. When exposed to an empty open field, Wistar rats spent more time in the outer area and made very low number of brief crossings in the central area. However, when an object occupied the central area, rats crossed frequently into and spent a long time in the central area. Administration of a range of different doses of methimepip (H3 receptor agonist reduced the entries into the central area with a novel object, indicating enhanced avoidance response. When balb/c mice were exposed to an open space 3D maze, neither methimepip nor JNJ-5207852 (H3 receptor antagonist/inverse agonist induced entry into the arms of the apparatus, indicative of lack of anxiolytic effects.

  4. Recovery of motor coordination after exercise is correlated to enhancement of brain-derived neurotrophic factor in lactational vanadium-exposed rats.

    Science.gov (United States)

    Wang, Dean-Chuan; Lin, Yu-Yi; Lin, Hwai-Ting

    2015-07-23

    Lactational exposure to vanadium can reduce the locomotor activity in adult animals. In this study, we investigated whether lactational vanadium exposure impairs the motor coordination and whether exercise ameliorates this dysfunction. Sprague-Dawley dams were treated with or without vanadium during lactation. The weaned male offspring were trained to treadmill running for 5 weeks and then examined their motor coordination on a rotarod. The neuroprotective effect of exercise was evaluated by the brain-derived neurotrophic factor (BDNF) in plasma and cerebellum. The results demonstrated that vanadium-exposed rats exhibited impaired motor coordination and reduced plasma and cerebellar BDNF levels. Treadmill running during childhood-adolescence prevented the impaired motor coordination in the lactational vanadium-exposed rats. The beneficial effect of treadmill running on motor coordination in the vanadium-exposed rats was correlated to the normalization of plasma and cerebellar BDNF levels, as well as the increased TrkB phosphorylation in the cerebellum. The result suggests that exercise may prevent the impairment of motor coordination in the lactational vanadium-exposed rats.

  5. Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro

    Institute of Scientific and Technical Information of China (English)

    Weihua Yan; Junze Liu

    2012-01-01

    Mitochondrial dysfunction is the key pathogenic mechanism of cerebral injury induced by high-altitude hypoxia. Some Chinese herbal monomers may exert anti-hypoxic effects through enhancing the efficiency of oxidative phosphorylation. In this study, effects of 10 kinds of Chinese herbal monomers on mitochondrial respiration and membrane potential of cerebral mitochondria isolated from hypoxia-exposed rats in vitro were investigated to screen anti-hypoxic drugs. Rats were exposed to a low-pressure environment of 405.35 mm Hg (54.04 kPa) for 3 days to establish high-altitude hypoxic models. Cerebral mitochondria were isolated and treated with different concentrations of Chinese herbal monomers (sinomenine, silymarin, glycyrrhizic acid, baicalin, quercetin, ginkgolide B, saffron, piperine, ginsenoside Rg1 and oxymatrine) for 5 minutes in vitro. Mitochondrial oxygen consumption and membrane potential were measured using a Clark oxygen electrode and the rhodamine 123 fluorescence analysis method, respectively. Hypoxic exposure significantly decreased the state 3 respiratory rate, respiratory control rate and mitochondrial membrane potential, and significantly increased the state 4 respiratory rate. Treatment with saffron, ginsenoside Rg1 and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rg1, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rg1, piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro.

  6. DEFECTS IN CERVICAL VERTEBRAE IN BORIC ACID-EXPOSED RAT EMBRYOS ARE ASSOCIATED WITH ANTERIOR SHIFTS OF HOX GENE EXPRESSION DOMAINS

    Science.gov (United States)

    Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of hox gene expression domainsNathalie Wery,1 Michael G. Narotsky,2 Nathalie Pacico,1 Robert J. Kavlock,2 Jacques J. Picard,1 AND Francoise Gofflot,1*1Unit of Developme...

  7. INTEGRATED DISINFECTION BY-PRODUCTS (DBP) MIXTURES RESEARCH: GENE EXPRESSION ALTERATIONS IN PRIMARY RAT HEPATOCYTE CULTURES EXPOSED TO DBP MIXTURES FORMED BY CHLORINATION AND OZONATION/POSTCHLORINATION

    Science.gov (United States)

    What is the study? This study was designed to provide data on the in vitro toxicity of water concentrates containing complex mixtures of DBPs. Rat hepatocytes in primary culture were exposed for 24 hr to full strength, 1:10 or 1:20 dilutions of chlorination or ozonation/chl...

  8. PULMONARY LOCALIZATION AND EXPRESSION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) IN HEALTHY OR HYPERTENSIVE RATS EXPOSED TO PARTICULATE MATTER (PM)

    Science.gov (United States)

    PULMONARY LOCALIZATION AND EXPRESSION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) IN HEALTHY OR HYPERTENSIVE RATS EXPOSED TO PARTICULATE MATTER (PM). GS Backus1, R Vincent2, UP Kodavanti2, 1Curriculum in Toxicology, UNC, Chapel Hill; 2NHEERL, ORD, US EPA, Research Triangle Park,...

  9. Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.

    Directory of Open Access Journals (Sweden)

    Olga Rafikova

    Full Text Available There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH. However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT, to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH.

  10. Pore alterations of the endothelial lining of rat fenestrated intestinal capillaries exposed to acute stress.

    Science.gov (United States)

    Aosa, Taishi; Chiba, Seiichi; Kitamura, Hirokazu; Ina, Keisuke; Tatsukawa, Shuji; Moriwaki, Chinatsu; Wei, Huixing; Gotoh, Koro; Masaki, Takayuki; Kakuma, Tetsuya; Shibata, Hirotaka; Fujikura, Yoshihisa

    2016-07-01

    Stress-induced inflammatory responses in the portal system are characterized by elevations in serum concentrations of interleukin-6 (IL-6) and endotoxins such as lipopolysaccharides (LPS). LPS translocation from the intestinal to the capillary lumen occurs via LPS endocytosis by the capillary endothelium. Because the capillary endothelium of the small intestinal submucosa is fenestrated, we determined the role of pore modifications within the fenestrated endothelium in relaying inflammatory stress responses in the portal vein. We evaluated changes in the diameter and density of endothelial pores of the lamina propria of intestinal villi induced by continuous light (CL) exposure for 48 h and the correlation between these changes and serum IL-6 concentration in the portal vein in a rat model. We found significant increases in both the pore diameter and density, accompanied by a significant increase in portal IL-6 concentration; these changes were significantly attenuated by pretreatment with propranolol, a beta adrenergic receptor antagonist. In contrast, intravenous noradrenaline administration mimicked CL-induced modifications of the diameter and density of pores and the elevation of portal vein IL-6 concentration. These findings suggested that stress-induced inflammatory responses in the portal system may be a part of the modifications of the endothelial pores triggered by sympathetic activation.

  11. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone.

    Science.gov (United States)

    Shende, Vishvesh H; McArthur, Simon; Gillies, Glenda E; Opacka-Juffry, Jolanta

    2015-01-01

    The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  12. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone

    Directory of Open Access Journals (Sweden)

    Vishvesh H. Shende

    2015-01-01

    Full Text Available The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally.

  13. HPA and sympathoadrenal activity of adult rats perinatally exposed to maternal mild calorie restriction.

    Science.gov (United States)

    Levay, Elizabeth A; Paolini, Antonio G; Govic, Antonina; Hazi, Agnes; Penman, Jim; Kent, Stephen

    2010-03-17

    Developmental programming of neuroendocrine systems is profoundly influenced by environmental cues such as caloric availability. The focus of investigations in this area has been on the effects of under- and malnutrition while there is a paucity of research examining the effects of more mild levels of calorie restriction (CR). Rat dams and their offspring were subjected to one of five dietary regimens: control, CR50% for 3 days preconception, CR25% during gestation, CR25% during lactation, and CR25% during gestation, lactation, and post-weaning (lifelong). Adult male offspring were decapitated and trunk blood collected to assay for basal concentrations of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT), as well as plasma concentrations of adrenalin (A) and noradrenalin (NA). Basal serum ACTH was reduced by 35-43% in all dietary regimens except the lifelong group. Although a similar trend was observed in the concentrations of serum CORT, only the decrease in the lactation group attained statistical significance. A was reduced by 33-49% as a result of all dietary regimens and NA was reduced in the gestation and lifelong groups by 51% and 39%, respectively. The potential mechanisms underlying these neuroendocrine alterations are discussed.

  14. The protective influence of selenium on oxidant disturbances in brain of rats exposed to lithium.

    Science.gov (United States)

    Kiełczykowska, M; Kocot, J; Lewandowska, A; Żelazowska, R; Musik, I

    2015-01-01

    For more than sixty years lithium carbonate has been used in medicine. However, during its administration different side effects including oxidative stress can occur. Selenium belongs to essential elements possessing antioxidant properties. This study aimed at evaluating if selenium could be used as a protective adjuvant in lithium therapy. The experiment was performed on four groups of Wistar rats: I (control), II (Li), III (Se), IV (Li + Se) treated with saline, lithium carbonate (2.7 mg Li/kg b.w.), sodium selenite (0.5 mg Se/kg b.w.) and lithium carbonate (2.7 mg Li/kg b.w.) + sodium selenite (0.5 mg Se/kg b.w.), respectively. All substances were administered as water solutions by stomach tube for 3 or 6 weeks. Catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as malonyldialdehyde (MDA) were determined in brain homogenates. Lithium slightly enhanced MDA and depressed CAT and SOD after 6 weeks as well as GPx after 3 weeks. Selenium co-administration showed tendency to restore the disturbed parameters. Selenium alone and given with lithium significantly increased GPx vs. Li-treated group after 3 weeks. Having regarded the outcomes of this study, the research on application of selenium during lithium treatment seems to be worth continuation.

  15. Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies

    Energy Technology Data Exchange (ETDEWEB)

    Brzoska, Malgorzata M.; Moniuszko-Jakoniuk, Janina [Department of Toxicology, Medical University of Bialystok, Mickiewicza 2c str., 15-222, Bialystok (Poland); Kaminski, Marcin; Supernak-Bobko, Dorota [Department of Histology and Embryology, Silesian School of Medicine, Medykow 20, 40-752, Katowice-Ligota (Poland); Zwierz, Krzysztof [Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Mickiewicza 2A, 15-222, Bialystok (Poland)

    2003-06-01

    We have created an experimental model using rats intoxicated with Cd administered in drinking water at the concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. The degree of kidney damage was evaluated biochemically and histopathologically. Sensitive biomarkers of Cd-induced proximal tubular injury such as urinary total N-acetyl-{beta}-d-glucosaminidase (NAG-T) and its isoenzyme B (NAG-B), and alkaline phosphatase (ALP) were used. Cd content in the kidney increased with the level and duration of exposure leading to dose- and time-dependent structural and functional renal failure. In rats exposed to 5 mg Cd/l, first symptoms of injury of the main tubules of long and short nephrons (structural damage to epithelial cells, increased urinary activities of NAG-T and NAG-B) were noted after 12 weeks of the experiment. The damage occurred at a low kidney Cd concentration amounting to 4.08{+-}0.33 {mu}g/g wet weight (mean {+-}SE) and a urinary concentration of 4.31{+-}0.28 {mu}g/g creatinine. On exposure to 50 mg Cd/l, damage to the main tubules (blurred structure of tubular epithelium, atrophy of brush border, partial fragmentation of cells with release of nuclei into tubular lumen as well as increased urinary activities of NAG-T, NAG-B and ALP) was already evident after 6 week s with the kidney Cd concentration of 24.09{+-}1.72 {mu}g/g wet weight. In rats exposed to 50 mg Cd/l, a lack of regular contour of glomeruli was noted after 12 weeks, whereas after 24 weeks thickening of capillary vessels and widening of filtering space were evident. After 24 weeks of exposure to Cd, increased urea concentration in the serum with simultaneous decrease in its level in the urine, indicating decreased clearance of urea, and increased excretion of total protein were observed, but endogenous creatinine clearance remained unaffected. At the lower exposure, symptoms of structural, but not functional, damage to the glomeruli were also evident after 24 weeks of the experiment. Our

  16. Ghrelin ameliorates catabolic conditions and respiratory dysfunction in a chronic obstructive pulmonary disease model of chronic cigarette smoke-exposed rats.

    Science.gov (United States)

    Kamiide, Yoshiyuki; Inomata, Norio; Furuya, Mayumi; Yada, Toshihiko

    2015-05-15

    Cigarette smoking, which is a well-known major risk factor for chronic obstructive pulmonary disease (COPD), causes both pulmonary and extrapulmonary abnormalities. Ghrelin is a gastric peptide that regulates energy homeostasis. In the present study, we investigated the effects of ghrelin on the catabolic changes, respiratory function and emphysema in an animal model of COPD induced by chronic exposure to cigarette smoke. Rats were exposed to cigarette smoke, and they were administered human ghrelin (0.1 or 1 mg/kg, subcutaneous, twice daily) for 12 weeks. Compared with air-exposed rats, body weight gain, food intake, food efficiency, tidal volume, peak expiratory flow rate, and forced expiratory volume at 100 ms were significantly lower, while functional residual capacity, lung capacity, and neutrophils in bronchoalveolar lavage fluid were significantly higher in cigarette smoke-exposed rats. These indicated that the systemic abnormalities associated with COPD developed after the exposure to cigarette smoke. Ghrelin significantly and dose-dependently increased the body weight gain and food efficiency in cigarette smoke-exposed rats. In ghrelin-treated rats, skeletal muscle strength, which tended to be lowered by cigarette smoke exposure, was improved. Ghrelin ameliorated respiratory function and emphysema in a dose-dependent manner, but did not inhibit the increase in neutrophils in the bronchoalveolar lavage fluid. The respiratory functional parameters and lung capacity were significantly correlated with body weight gain. These results suggest that ghrelin inhibited the development of the catabolic changes, respiratory dysfunction, and emphysema that were induced by cigarette smoke exposure in rats, at least in part, through the amelioration of nutritional status. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. [Long-term changes in adaptive behavior of rats after neonatal inflammatory pain].

    Science.gov (United States)

    Mikhailenko, V A; Butkevich, I P; Vershinina, E A; Ulanova, N A

    2015-01-01

    In this study we addressed the tonic nociceptive system functional activity in the formalin test, anxiety- and depression-like behaviors and spatial learning in adolescent male rats exposed in the neonatal development to repeated inflammatory pain peripheral stimulation. The following groups of 25-day-old rats were used after being exposed on days 7 and 8 to: 1) formalin-induced inflammatory pain with maternal separation for 60 min (FS), 2) the same inflammatory pain stimulation without maternal separation (FWS), 3) physiological saline injection with maternal separation for 1 h (SS), 4) physiological saline injection without maternal separation (SWS) and 5) no stimulation (intact rats). The data obtained indicate that pain caused in 7-8-day-old rat pups by formalin injection into the plantar pad of the hind paw manifests by adolescence (day 25 as a strengthened inflammatory response under the analogous painful stimulation in the formalin test, adaptive behavior disorder in the forced swimming test and spatial learning disability. Our findings that a short-term repeated maternal deprivation of the 7-8-day-old rat pups without inflammatory pain increases the depression-like behavior are also of particular interest. Thus, a repeated inflammatory pain during the neonatal development brings about significant changes in the adaptive behaviors studied as well as in spatial learning in adolescent rats.

  18. Persistent Expression Changes of Fibrosis-Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

    Science.gov (United States)

    Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Yeshitla, Samrawit A.; Wu, Honglu; Meyers, Valerie; James, John T.

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust-induced changes of the expression of fibrosis-related genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphate-buffered saline (PBS). A zymosan-induced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using real-time PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose- and time-dependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the

  19. Exogenous sphingosine-1-phosphate boosts acclimatization in rats exposed to acute hypobaric hypoxia: assessment of haematological and metabolic effects.

    Directory of Open Access Journals (Sweden)

    Sonam Chawla

    Full Text Available BACKGROUND: The physiological challenges posed by hypobaric hypoxia warrant exploration of pharmacological entities to improve acclimatization to hypoxia. The present study investigates the preclinical efficacy of sphingosine-1-phosphate (S1P to improve acclimatization to simulated hypobaric hypoxia. EXPERIMENTAL APPROACH: Efficacy of intravenously administered S1P in improving haematological and metabolic acclimatization was evaluated in rats exposed to simulated acute hypobaric hypoxia (7620 m for 6 hours following S1P pre-treatment for three days. MAJOR FINDINGS: Altitude exposure of the control rats caused systemic hypoxia, hypocapnia (plausible sign of hyperventilation and respiratory alkalosis due to suboptimal renal compensation indicated by an overt alkaline pH of the mixed venous blood. This was associated with pronounced energy deficit in the hepatic tissue along with systemic oxidative stress and inflammation. S1P pre-treatment improved blood oxygen-carrying-capacity by increasing haemoglobin, haematocrit, and RBC count, probably as an outcome of hypoxia inducible factor-1α mediated erythropoiesis and renal S1P receptor 1 mediated haemoconcentation. The improved partial pressure of oxygen in the blood could further restore aerobic respiration and increase ATP content in the hepatic tissue of S1P treated animals. S1P could also protect the animals from hypoxia mediated oxidative stress and inflammation. CONCLUSION: The study findings highlight S1P's merits as a preconditioning agent for improving acclimatization to acute hypobaric hypoxia exposure. The results may have long term clinical application for improving physiological acclimatization of subjects venturing into high altitude for occupational or recreational purposes.

  20. Effect of ascorbic acid supplementation on nitric oxide metabolites and systolic blood pressure in rats exposed to lead.

    Science.gov (United States)

    Mohammad, Amani; Ali, Noroozzadeh; Reza, Badalzadeh; Ali, Khoshbaten

    2010-04-01

    Extended exposure to low levels of lead causes high blood pressure in human and laboratory animals. The mechanism is not completely recognized, but it is relatively implicated with generation of free radicals, oxidant agents such as ROS, and decrease of available nitric oxide (NO). In this study, we have demonstrated the effect of ascorbic acid as an antioxidant on nitric oxide metabolites and systolic blood pressure in rats exposed to low levels of lead. The adult male Wistar rats weighing 200-250 g were divided into four groups: control, lead acetate (receiving 100 ppm lead acetate in drinking water), lead acetate plus ascorbic acid (receiving 100 ppm lead acetate and 1 g/l ascorbic acid in drinking water), and ascorbic acid (receiving 1 g/l ascorbic acid in drinking water) groups. The animals were anesthetized with ketamin/xylazine (50 and 7 mg/kg, respectively, ip) and systolic blood pressure was then measured from the tail of the animals by a sphygmomanometer. Nitric oxide levels in serum were measured indirectly by evaluation of its stable metabolites (total nitrite and nitrate (NOchi)). After 8 and 12 weeks, systolic blood pressure in the lead acetate group was significantly elevated compared to the control group. Ascorbic acid supplementation could prevent the systolic blood pressure rise in the lead acetate plus ascorbic acid group and there was no significant difference relative to the control group. The serum NOchi levels in lead acetate group significantly decreased in relation to the control group, but this reduction was not significantly different between the lead acetate plus ascorbic acid group and the control group. Results of this study suggest that ascorbic acid as an antioxidant prevents the lead induced hypertension. This effect may be mediated by inhibition of NOchi oxidation and thereby increasing availability of NO.

  1. Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects

    Science.gov (United States)

    Chawla, Sonam; Rahar, Babita; Singh, Mrinalini; Bansal, Anju; Saraswat, Deepika; Saxena, Shweta

    2014-01-01

    Background The physiological challenges posed by hypobaric hypoxia warrant exploration of pharmacological entities to improve acclimatization to hypoxia. The present study investigates the preclinical efficacy of sphingosine-1-phosphate (S1P) to improve acclimatization to simulated hypobaric hypoxia. Experimental Approach Efficacy of intravenously administered S1P in improving haematological and metabolic acclimatization was evaluated in rats exposed to simulated acute hypobaric hypoxia (7620m for 6 hours) following S1P pre-treatment for three days. Major Findings Altitude exposure of the control rats caused systemic hypoxia, hypocapnia (plausible sign of hyperventilation) and respiratory alkalosis due to suboptimal renal compensation indicated by an overt alkaline pH of the mixed venous blood. This was associated with pronounced energy deficit in the hepatic tissue along with systemic oxidative stress and inflammation. S1P pre-treatment improved blood oxygen-carrying-capacity by increasing haemoglobin, haematocrit, and RBC count, probably as an outcome of hypoxia inducible factor-1α mediated erythropoiesis and renal S1P receptor 1 mediated haemoconcentation. The improved partial pressure of oxygen in the blood could further restore aerobic respiration and increase ATP content in the hepatic tissue of S1P treated animals. S1P could also protect the animals from hypoxia mediated oxidative stress and inflammation. Conclusion The study findings highlight S1P’s merits as a preconditioning agent for improving acclimatization to acute hypobaric hypoxia exposure. The results may have long term clinical application for improving physiological acclimatization of subjects venturing into high altitude for occupational or recreational purposes. PMID:24887065

  2. Effect of ascorbic acid supplementation on nitric oxide metabolites and systolic blood pressure in rats exposed to lead

    Directory of Open Access Journals (Sweden)

    Mohammad Amani

    2010-01-01

    Full Text Available Background: Extended exposure to low levels of lead causes high blood pressure in human and laboratory animals. The mechanism is not completely recognized, but it is relatively implicated with generation of free radicals, oxidant agents such as ROS, and decrease of available nitric oxide (NO. In this study, we have demonstrated the effect of ascorbic acid as an antioxidant on nitric oxide metabolites and systolic blood pressure in rats exposed to low levels of lead. Materials and Methods: The adult male Wistar rats weighing 200-250 g were divided into four groups: control, lead acetate (receiving 100 ppm lead acetate in drinking water, lead acetate plus ascorbic acid (receiving 100 ppm lead acetate and 1 g/l ascorbic acid in drinking water, and ascorbic acid (receiving 1 g/l ascorbic acid in drinking water groups. The animals were anesthetized with ketamin/xylazine (50 and 7 mg/kg, respectively, ip and systolic blood pressure was then measured from the tail of the animals by a sphygmomanometer. Nitric oxide levels in serum were measured indirectly by evaluation of its stable metabolites (total nitrite and nitrate (NOc. Results: After 8 and 12 weeks, systolic blood pressure in the lead acetate group was significantly elevated compared to the control group. Ascorbic acid supplementation could prevent the systolic blood pressure rise in the lead acetate plus ascorbic acid group and there was no significant difference relative to the control group. The serum NOc levels in lead acetate group significantly decreased in relation to the control group, but this reduction was not significantly different between the lead acetate plus ascorbic acid group and the control group. Conclusion: Results of this study suggest that ascorbic acid as an antioxidant prevents the lead induced hypertension. This effect may be mediated by inhibition of NOc oxidation and thereby increasing availability of NO.

  3. Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

    Science.gov (United States)

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation.

  4. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lip