Elevated Liver Enzymes

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Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

Ethosuximide: liver enzyme induction and D-glucaric acid excretion.

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Gilbert, J C; Scott, A K; Galloway, D B; Petrie, J C

1974-06-01

1 A study has been carried out to determine if ethosuximide induces liver enzymes. 2 Ethosuximide did not affect the urinary excretion of D-glucaric acid by healthy adult subjects nor was the mean daily D-glucaric acid excretion of three epileptic children on long term ethosuximide therapy different from that of three matched controls. 3 Ethosuximide (10 mg/kg or 50 mg/kg daily) did not influence D-glucaric acid excretion or liver microsomal protein and cytochrome P450 contents of guinea pigs but at a dose of 100 mg/kg daily in rats it increased liver microsomal protein and cytochrome P450 without altering D-glucaric acid excretion. 4 These results suggest that at anticonvulsant doses ethosuximide is unlikely to induce liver enzymes. The precise relationship between D-glucaric acid excretion and liver enzyme induction remains in doubt.

The Effect of Myrtus communis Extract on Liver Enzymes and Blood Biochemical Factors in Diabetic Adult Male Rats

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Habiballah Johari

2014-10-01

Full Text Available Background: The aim of this study was the effect of Myrtus communis extract on liver enzymes and blood biochemical factors in diabetic adult male rats. Materials and Methods: This study has been carried out experimentally and completely random. Seventy adult male Wistar rats were divided in 7 groups including: control which received no treatment, sham who received 2 mL of distilled water, the 1st, 2nd and 3rd experimental groups which received 0.75, 1.5 and 3 mg/kg Myrtus communis leaf extract respectively, the 4th experimental group as the diabetic control group who received streptozotocin (60 mg/kg and the 5th experimental group as the diabetic treatment group who received 3 mg/kg of extract. This experiment lasted 14 days with prescript orally. After this period, all the rats, were weighted, anesthetized and blood samples were taken from the heart centrifuged and sera were evaluated for the concentration of various factors. In addition liver were removed and sliced. Results: According to the obtained results, the plasma concentration of liver enzyme (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, cholesterol and glucose presented a significant decrease at (p≤0.05. Whereas no significant change were seen in body weight, triglyceride, urea, albumin and total protein. Histological studies of the liver tissue showed no significant difference among various groups. Conclusion: Myrtus communis is comprise of collections of flavonoids and other various components with antioxidant and anti inflammatory properties. Thence it can effective in treatment of liver diseases and decrease of blood sugar and cholesterol in diabetes mellitus patients.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

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Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

2014-01-01

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Long-term effect of medium-chain triglyceride on hepatic enzymes catalyzing lipogenesis and cholesterogenesis in rats

International Nuclear Information System (INIS)

Takase, Sachiko; Morimoto, Ayami; Nakanishi, Mayumi; Muto, Yasutoshi.

1977-01-01

This study was conducted to investigate the long-term effect of dietary medium-chain triglyceride (MCT) as compared with that of corn oil feeding on lipid metabolism in rats. Both serum cholesterol and triglyceride levels in MCT-fed rats showed significant decrease during the experimental period of eight weeks, although liver cholesterol and triglyceride contents were not distinguishable between the two groups. Significant elevation of the activity of lipogenic enzymes, such as fatty acid synthetase (FAS) and malic enzyme (ME) of the liver, was observed in MCT-fed rats without any fat accumulation of the liver (fatty liver). The increase of lipogenic enzyme activity was accompanied by a significant reduction of essential fatty acids (EFA) such as 18:2 (ωsigma) and 20:4 (ωsigma) in total liver lipid. In contrast, hepatic β-hydroxy-β-methylglutaryl CoA(HMG-CoA) reductase activity was significantly decreased in MCT-fed rats, that would play an important role in achieving hypocholesterolemia. From these results obtained in a long-term experiment, it is concluded that exogenous MCT depresses the key enzyme catalyzing cholesterol synthesis with a concomitant elevation of lipogenic enzyme activity in the rat liver. (auth.)

Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

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Nor Aziyah Mat-Rahim

2017-01-01

Full Text Available Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08 were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA. These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP and gamma-glutamyl transferase (GGT levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x and level of GGT (more than 2x in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.

Effect of propylthiouracil on 125I-L-triiodothyronine binding to the nuclei and on malic enzyme activity in rat liver cytosol

International Nuclear Information System (INIS)

Knopp, J.

1980-01-01

The effects of propylthiouracil (PTU), triiodothyronine (T 3 ) and thyroxine (T 4 ) on the malic enzyme activity of rat liver cytosol and on the binding of 125 I-L-triiodothyronine to the nuclear fraction were examined. A significant decrease in in vitro binding of 125 I-T 3 to the liver nuclei was found in rats fed PTU for 12 h, 24 h and 120 h. The hepatic malic enzyme activity was unchanged after 12 h, but markedly decreased after 24 h and 120 h of PTU treatment. In 120 h PTU fed animals the effect of T 3 on the malic enzyme activity was five times higher in comparison with an equimolar dose of T 4 . Finally, the effect of T 4 on the malic enzyme activity was observed which might result from the intrinsic activity of T 4 under the conditions of a decreased T 4 to T 3 conversion due to the PTU feeding. The obtained results show that there is a certain correlation between the nuclear T 3 binding and the cytosol malic enzyme activity which is presumably induced directly through the m-RNA synthesis stimulated by thyroid hormones. (author)

ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

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N. I. Burmas

2016-05-01

Full Text Available Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin affection and chromium (potassium dichromate intoxication. Methods. The experimental affection of rats of different ages was performed by combined injection of hexavalent chromium compounds (a solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg. On the 7th and 14th days the rats were injected with enterosorbent Sorbex (150 mg/kg. Enzyme markers activity of the liver was evaluated due to alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP rates. Bile formation function of the liver was evaluated by total bilirubin and bile acids content in blood. Results. The disorders in hepatocytes plasma membranes permeability were defined by the increased rates of ALT, AST and alkaline phosphatase in blood serum which were decreased in the liver. It was determined that total bilirubin and bile acids content in blood serum of the affected animals increased. It influenced hepatocytes excretion in bile capillaries and caused cholestasis and revenues decrease in bile. Conclusions. The most significant metabolic disorders in cases of chrome-isoniazid-rifampicin affection were defined in immature and senior animals in comparison with mature animals.

Changes in activities of adaptive liver enzymes in rats after non-lethal x-irradiation

International Nuclear Information System (INIS)

Toropila, M.; Ahlersova, E.; Ahlers, I.; Benova, K.

1998-01-01

The effect of a single dose of whole-body X-irradiation of 2.39 Gy (250 R) on the activities of selected adaptive rat liver enzymes and blood serum corticosterone concentrations was followed for a period of 28 days. Rats of Wistar strain SPF breeding (VELAZ Prague) were used. Both irradiated and control animals were fed in pairs with the same amount of feed as was consumed by irradiated animals in the pilot experiment. The feed intake of irradiated animals decreased significantly until the fourth day. During the rest of the experimental period no significant differences were recorded in feed intake between the experimental and control groups. The activity of tyrosine aminotransferase (TAT) in the liver of irradiated animals increased, with the exception of the initial period. Similar changes were recorded in the activity of tryptophane-2-3 dioxygenase (TO). A significant increase on the third day and a significant decrease from the seventh day after irradiation was recorded in the activity of aspartate aminotransferase (AST). Similar changes were observed with alanine aminotransferase (ALT). It is necessary to stress that the activity of this enzyme decreased also on the first day after irradiation. Until the third day there was a marked increase of serum corticosterone in the irradiated animals. The results point not only towards significant changes to the parameters observed, caused by a non-lethal irradiation dose, but also towards the importance of the nutritional regime, so-called paired feeding

Peroxisomal enzymes in the liver of rats with experimental diabetes mellitus type 2.

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Turecký, L; Kupčová, V; Uhlíková, E; Mojto, V

2014-01-01

Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b(5) reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy.

Effects of Artemisia dracunculus Aqueous Extract on Blood Sugar, Serum Insulin, Triglyceride and Liver Enzymes in Fructose Drinking Water Male Rats

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Mohammad Reza Shahraki

2017-02-01

Full Text Available Background Artemisia are various groups of plants which are used as an herbal medicine in all countries; the present study was designed to evaluate the effects of Artemisia dracunculus (AD leaves aqueous extract on blood sugar, serum insulin, and triglyceride and liver enzymes in Fructose Drinking water (FDW male rats. Methods At the beginning of experiment, 48 Wistar-albino male rats, weighing 200 - 250g were divided into control (C and FDW groups (n = 24. FDW group received FDW (10%, w/v for a month but control group did not receive any agents during the trial period. A half of control and FDW groups received AD L aqueous extract daily during trial period. At the end, animals were anesthetized, sacrificed and blood samples were collected from cervical vessels. Serum insulin, Blood glucose, insulin resistance index, triglyceride and liver enzymes were measured by ordinary methods. Obtained data were analyzed using SPSS-17 via one way ANOVA and Tukey tests. Results Our results showed that serum insulin, blood sugar, insulin resistance index, triglyceride, Aspartate amino transferase (AST and Alanine amino transferase (ALT values in FDW group significantly increased compared to C and C + E groups but these values in group FDW + E were significantly decreases compared to group FDW (P < 0.001. Conclusions Our findings demonstrated that AD L aqueous extract improves blood sugar, serum insulin, insulin resistance index and liver enzymes in rat model.

EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

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Nádia Araújo Miguel

2016-07-01

Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

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N. I. Burmas; L. S. Fira; P. H. Lyhackyy

2016-01-01

Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin) affection and chromium (p...

Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

International Nuclear Information System (INIS)

Theron, C.N.

1985-03-01

A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

Prostaglandin levels and lysosomal enzyme activities in irradiated rats

International Nuclear Information System (INIS)

Trocha, P.J.; Catravas, G.N.

1980-01-01

Whole-body irradiation of rats results in the release of hydrolases from lysosomes, an increase in lysosomal enzyme activities, and changes in the prostaglandin levels in spleen and liver tissues. A transient increase in the concentration of prostaglandins E and F and leakage of lysosomal hydrolases occurred in both spleen and liver tissues 3-6 hours after the animals were irradiated. Maximal values for hydrolase activities, prostaglandin E and F content, and release of lysosomal enzymes were found 4 days postirradiation in rat spleens whereas in the liver only slight increases were observed at this time period for prostaglandin F levels. On day 7 there was a final rise in the spleen's prostaglandin E and F concentrations and leakage of hydrolases from the lysosomes before returning to near normal values on day 11. The prostaglandin F concentration in liver was also slightly elevated on the 7th day after irradiation and then decreased to control levels. (author)

Rat liver contains a limited number of binding sites for hepatic lipase

NARCIS (Netherlands)

G.C. Schoonderwoerd (Kees); A.J.M. Verhoeven (Adrie); H. Jansen (Hans)

1994-01-01

textabstractThe binding of hepatic lipase to rat liver was studied in an ex vivo perfusion model. The livers were perfused with media containing partially purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the

Coenzyme metabolism in rat liver transketolase

International Nuclear Information System (INIS)

Gorbach, Z.V.; Kubyshin, V.L.; Maglysh, S.S.; Zabrodskaya, S.V.

1987-01-01

On the basis of the results of kinetic investigations, two binding sites for hydroxythiamine diphosphate were determined in apotransketolase, with sharply differing values of K/sub i/: (7-22) x 10 -9 and (13.0-19.7) x 10 -8 M. A study was made of the turnover rate of thiamine diphosphate in holotransketolase in rat liver tissue by a radioisotope method, using [ 14 C] thiamine as the labeled precursor. The half-substitution time and rate constant of degradation of the coenzyme in transketolase are close in absolute values to the analogous indices for the protein portion of the enzyme and constitute 153 h and 0.108 day -1 , respectively. Rat liver transketolase exists in vivo in the form of a substituted α-carbanion. Replacement of thiamine diphosphate by hydroxythiamine diphosphate in the holoenzyme has no effect on the formation of the intermediate α-carbanion form of the enzyme

Threonine phosphorylation of rat liver glycogen synthase

International Nuclear Information System (INIS)

Arino, J.; Arro, M.; Guinovart, J.J.

1985-01-01

32 P-labeled glycogen synthase specifically immunoprecipitated from 32 P-phosphate incubated rat hepatocytes contains, in addition to [ 32 P] phosphoserine, significant levels of [ 32 P] phosphothreonine. When the 32 P-immunoprecipitate was cleaved with CNBr, the [ 32 P] phosphothreonine was recovered in the large CNBr fragment (CB-2, Mapp 28 Kd). Homogeneous rat liver glycogen synthase was phosphorylated by all the protein kinases able to phosphorylate CB-2 in vitro. After analysis of the immunoprecipitated enzyme for phosphoaminoacids, it was observed that only casein kinase II was able to phosphorylate on threonine and 32 P-phosphate was only found in CB-2. These results demonstrate that rat liver glycogen synthase is phosphorylated at threonine site(s) contained in CB-2 and strongly indicate that casein kinase II may play a role in the ''in vivo'' phosphorylation of liver glycogen synthase. This is the first protein kinase reported to phosphorylate threonine residues in liver glycogen synthase

Influence of Chloramphenicol and Amoxicillin on Rat Liver ...

African Journals Online (AJOL)

This study examined the effect of chloramphenicol and amoxicillin on liver microsomal enzymes Ca2+-ATPase and Glucose-6-Phosphatase (G-6-P) and lipid peroxidation in rats. Male Wistar strain rats weighing 120 – 195 g were divided into four groups. Group one, the control group, received physiological saline, group ...

Pharmacokinetic study of isocorynoxeine metabolites mediated by cytochrome P450 enzymes in rat and human liver microsomes.

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Zhao, Lizhu; Zang, Bin; Qi, Wen; Chen, Fangfang; Wang, Haibo; Kano, Yoshihiro; Yuan, Dan

2016-06-01

Isocorynoxeine (ICN) is one of the major bioactive tetracyclic oxindole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks. that is widely used for the treatment of hypertension, vascular dementia, and stroke. The present study was undertaken to assess the plasma pharmacokinetic characteristics of major ICN metabolites, and the role of simulated gastric and intestinal fluid (SGF and SIF), human and rat liver microsomes (HLMs and RLMs), and seven recombinant human CYP enzymes in the major metabolic pathway of ICN. A rapid, sensitive and accurate UHPLC/Q-TOF MS method was validated for the simultaneous determination of ICN and its seven metabolites in rat plasma after oral administration of ICN at 40mg/kg. It was found that 18.19-dehydrocorynoxinic acid (DCA) and 5-oxoisocorynoxeinic acid (5-O-ICA) were both key and predominant metabolites, rather than ICN itself, due to the rapid and extensive metabolism of ICN in vivo. The further study indicated that ICN was mainly metabolized in human or rat liver, and CYPs 2C19, 3A4 and 2D6 were the major enzymes responsible for the biotransformation of ICN to DCA and 5-O-ICA in human. These findings are of significance in understanding of the pharmacokinetic nature of tetracyclic oxindole alkaloids, and provide helpful information for the clinical co-administration of the herbal preparations containing U. rhynchophylla with antihypertensive drugs that are mainly metabolized by CYP3A4 and CYP2C19. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Titanium Dioxide Nanoparticles on The Amount of Blood Cells and Liver Enzymes in Wistar Rats

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Rezaei Zarchi

2011-11-01

Full Text Available Introduction: Considering the development of nanotechnology and extensive use of nano-materials are in different fields of industry, it is necessary to investigate their destructive effects on biological systems. Titanium dioxide(TiO2 is used in the production of different dyes, cosmetics, ceramics, photocatalysts, water and sewage treatment and a lot of other products. In the present study, the effect of TiO2 on the number of blood cells and the activity of liver enzymes of rat was assessed. Methods: Concentrations of 50, 100 and 500 mg/Kg TiO2 nanoparticles (25 nm size in distilled water were administered orally to Wistar rats for 14 days and some blood factors were studied on the blood samples collected. Results: Results showed that TiO2 nanoparticles cause different changes in blood cells, and the changes were significant for some of them such as white blood cells (lymphocytes, monocytes, eosinophils and basophils. Decreased number of red blood cells and increased level of liver enzymes was also observed after the administration of different concentrations of TiO2, which proves the toxic effects of TiO2 on the body. Conclusion: Results of the present study proved the toxicity of TiO2 nanoparticles on the living organisms. So, further studies are recommended to predict TiO2 toxicity.

Changes at transcriptional level during liver regeneration in the rat

International Nuclear Information System (INIS)

Subba Rao, M.N.; Netrawali, M.S.; Pradhan, D.S.; Sreenivasan, A.

1976-01-01

A great upheaval in RNA synthetic pattern is known to occur during the early periods after partial hepatectomy. Such changes are being studied in regenerating rat liver with a view to understanding regulatory mechanisms of eukaryotic transcription. Follwoing partial hepatectomy, RNA synthesis is rat liver showed graded increase during 4 to 18 hours. At these time intervals, a significant enhancement could be discerned both in template efficiency of chromatin and in RNA polymerase activity in this tissue. Further examination revealed that the activity of RNA polymerase II (extra-nucleolar enzyme) stimulated to a much greater extent as compared to that of RNA polymerase I (nucleolar enzyme). Partial hepatectomy also resulted in significant alterations in turnovers of chromosomal acidic proteins in liver. 32 P-orthophosphate injected intraperitoneally was used in these studies. (author)

A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

Science.gov (United States)

Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud

2017-07-01

Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (Pbile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of x-irradiation on the activity of the key enzymes of the synthesis and degradation of heme in rat liver

International Nuclear Information System (INIS)

Deev, L.I.; Topchishvili, G.I.; Akhalaya, M.Ya.; Platonov, A.G.

1985-01-01

For Wistar rat males the effect of X radiation on the activity of delta-aminolevuminatesynthase and chemoxygenase - the rate of limiting enzymes of synthesis and catabolism of heme, as well as the level of ''free'' (non-utilized) heme in the rat liver are studied. The animals were irradiated using the X-ray device with the dose rate 0.5 Gy/min. X irradiation in the minimum lethal dose (7 Gy) caused evident changes in the activity of delta-aminolevuminatesynthase and chemoxygenase in the rat liver. Already one day after irradiation a noticeable decrease in the activity of delta-aminoleviminatesynthase (up to 81% of the normal one) was observed, and the maximum decrease took place on the third day (49% of the norm). On the 5-7-th day partial normalization of the activity of delta-aminoleviminatesynthase occurred. The chemoxygenase activity at the initial period after irradiation (1 day after) increased, after that (on the 5-7-th day), the phase of more than twofold and prolonged increase in the enzyme activity followed. Irradiation of animals by the dose of 5 Gy did not induce reliable changes in the activity of chemoxygenase and caused a considerably lower decrease in the activity of delta-aminolevunatesynthase. The observed suppression of synthesis and increase in heme catabolism do not result in the decrease in the level of ''free'' heme in the liver of irradiated animals. The conclusion is made on the presence of considerable violations of heme metabolism in the liver of irradiated animals, however, there is no final answer to the question on the role of detected effects in the decrease of microsomal level of cytochrome R-450

Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

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Sana Chakroun

2017-12-01

Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

Isolation and purification of rat liver morphine UDP-glucuronosyltransferase

International Nuclear Information System (INIS)

Puig, J.F.; Tephly, T.R.

1986-01-01

The enhancement of rat liver microsomal morphine (M) and 4-hydroxybiphenyl (4-HBP) UDP-glucuronyltransferase (UDPGT) activities by phenobarbital treatment has been proposed to represent increased activity of a single enzyme form, GT-2. They have separated M and 4-HBP UDPGT activities from Emulgen 911-solubilized microsomes obtained from livers of phenobarbital-treated Wistar rats. A sensitive assay procedure was developed to quantify M-UDPGT and 4-HBP-UDPGT activities using 14 C-UDP-glucuronic acid (UDPGA) and reversed phase C-18 minicolumns whereby the radioactive glucuronides were differentially eluted from labeled UDPGA. Trisacryl DEAE, and chromatofocusing procedures were employed to separate M-UDPGT and 4-HBP-UDPGT in the presence of exogenous phosphatidylcholine (PC). The PC is necessary to stabilize UDPGT activities. M-UDPGT was isolated to apparent homogeneity and displayed a monomeric molecular weight of 56,000 daltons on SDS-PAGE. It reacted with M but not with 4-HBP, bilirubin, p-nitrophenol, testosterone, androsterone, estrone, 4-aminobiphenyl or α-naphthylamine. 4-HBP-UDPGT did not react with M. Therefore, M and 4-HBP glucuronidations are catalyzed by separate enzymes in rat liver microsomes

Regulation of N-nitrosodimethylamine demethylase in rat liver and kidney.

Science.gov (United States)

Hong, J Y; Pan, J M; Dong, Z G; Ning, S M; Yang, C S

1987-11-15

In previous work, the low Km form of N-nitrosodimethylamine (NDMA) demethylase has been demonstrated to be due to a specific form of cytochrome P-450 (designated as P-450ac) and to be the enzyme required for the metabolic activation of NDMA. The present work deals with the regulation of P-450ac in rat liver during development as well as the mechanism of induction of P-450ac in rat liver and kidney by inducers. NDMA demethylase activity was almost undetectable in the liver of newborn rats, increased after day 4, and remained elevated throughout the first 17 days of the neonatal period. The enhancement of NDMA demethylase activity during development was accompanied by corresponding increases of P-450ac content and P-450ac mRNA levels as determined by Western and slot blot analyses, respectively. No sex differences with respect to this enzyme were observed in the developing rats. Acetone treatment on late-term pregnant rats for 2 days resulted in transplacental inductions of P-450ac and P-450ac mRNA in the newborn rats. Pretreatment of young male rats and adult female rats with acetone or isopropyl alcohol caused increases of NDMA demethylase activity and P-450ac content in the liver but no significant change in the P-450ac mRNA level. These facts suggest the possible existence of a posttranscription regulatory mechanism under these induction conditions. The presence of P-450ac in rat kidney was demonstrated by Western and Northern blot analyses. The renal form of P-450ac seemed to be regulated in a fashion similar to the hepatic P-450ac regarding its response to inducing factors such as fasting and acetone treatment.

The antioxidant effects of vitamin C on liver enzymes: aspartate aminotransferase, alanine aminotranferease, alkaline phosphatase and gamma-glutamyltransferase activities in rats under Paraquat insult

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Benjamin Nnamdi Okolonkwo

2013-06-01

Full Text Available Paraquat (PQ is a bipyridylium herbicide; applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the liver enzymes [aspartate aminotransferase (SGOT, alanine aminotranferease (SGPT, alkaline phosphatase (ALP, and gamma-glutamyltransferase (GGT] of rats under this toxic insult. Male rats in groups (A, B, C and D were intraperitoneally injected with different sublethal increasing doses (0, 0.02, 0.04 and 0.06 g/kg body weigh of PQ respectively on monthly basis. Subsequently, the subgroups (A2, B2, C2 and D2 were given orally, 200 mg/L vitamin C, while the subgroups A1, B1, C1, and D1, received only water. Four animals per subgroup were decapitated on monthly basis and blood samples taken for enzyme assay. The parameters studied were - SGOT, SGPT, ALP and GGT - liver enzymes. The dose and time dependent PQ toxicity effect resulted in highly elevated Liver enzymes activities. The subgroups on vitamin C had significantly lower enzyme activities when compared to the same subgroups on only PQ insult. But the values were high when compared to the control subgroups (A1 and A2. These results were indication that vitamin C when given at moderate doses and maintained for a longer period could be a life saving adjunct to toxic insult.

Purification and characterization of rat liver minoxidil sulphotransferase.

Science.gov (United States)

Hirshey, S J; Falany, C N

1990-01-01

Minoxidil (Mx), a pyrimidine N-oxide, is used therapeutically as an antihypertensive agent and to induce hair growth in patients with male pattern baldness. Mx NO-sulphate has been implicated as the agent active in producing these effects. This paper describes the purification of a unique sulphotransferase (ST) from rat liver cytosol that is capable of catalysing the sulphation of Mx. By using DEAE-Sepharose CL-6B chromatography, hydroxyapatite chromatography and ATP-agarose affinity chromatography, Mx-ST activity was purified 240-fold compared with the activity in cytosol. The purified enzyme was also capable of sulphating p-nitrophenol (PNP) at low concentrations (less than 10 microM). Mx-ST was purified to homogeneity, as evaluated by SDS/PAGE and reverse-phase h.p.l.c. The active form of the enzyme had a molecular mass of 66,000-68,000 Da as estimated by gel exclusion chromatography and a subunit molecular mass of 35,000 Da. The apparent Km values for Mx, 3'-phosphoadenosine 5'-phosphosulphate and PNP were 625 microM, 5.0 microM and 0.5 microM respectively. However, PNP displayed potent substrate inhibition at concentrations above 1.2 microM. Antibodies raised in rabbits to the pure enzyme detected a single band in rat liver cytosol with a subunit molecular mass of 35,000 Da, as determined by immunoblotting. The anti-(rat Mx-ST) antibodies also reacted with the phenol-sulphating form of human liver phenol sulphotransferase, suggesting some structural similarity between these proteins. Images Fig. 5. Fig. 6. Fig. 7. PMID:2241904

Actions of p-synephrine on hepatic enzyme activities linked to carbohydrate metabolism and ATP levels in vivo and in the perfused rat liver.

Science.gov (United States)

Maldonado, Marcos Rodrigues; Bracht, Lívia; de Sá-Nakanishi, Anacharis Babeto; Corrêa, Rúbia Carvalho Gomes; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar

2018-01-01

p-Synephrine is one of the main active components of the fruit of Citrus aurantium (bitter orange). Extracts of the bitter orange and other preparations containing p-synephrine have been used worldwide to promote weight loss and for sports performance. The purpose of the study was to measure the action of p-synephrine on hepatic enzyme activities linked to carbohydrate and energy metabolism and the levels of adenine mononucleotides. Enzymes and adenine mononucleotides were measured in the isolated perfused rat liver and in vivo after oral administration of the drug (50 and 300 mg/kg) by using standard techniques. p-Synephrine increased the activity of glycogen phosphorylase in vivo and in the perfused liver. It decreased, however, the activities of pyruvate kinase and pyruvate dehydrogenase also in vivo and in the perfused liver. p-Synephrine increased the hepatic pools of adenosine diphosphate and adenosine triphosphate. Stimulation of glycogen phosphorylase is consistent with the reported increased glycogenolysis in the perfused liver and increased glycemia in rats. The decrease in the pyruvate dehydrogenase activity indicates that p-synephrine is potentially capable of inhibiting the transformation of carbohydrates into lipids. The capability of increasing the adenosine triphosphate-adenosine diphosphate pool indicates a beneficial effect of p-synephrine on the cellular energetics. Copyright © 2017 John Wiley & Sons, Ltd.

Dipeptidylpeptidase-­IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

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E. Tarantola

2012-10-01

Full Text Available Given the scarcity of donors, moderately fatty livers (FLs are currently being considered as possible grafts for orthotopic liver transplantation (OLT, notwithstanding their poor tolerance to conventional cold preservation. The behaviour of parenchymal and sinusoidal liver cells during transplantation is being studied worldwide. Much less attention has been paid to the biliary tree, although this is considered the Achille’s heel even of normal liver transplantation. To evaluate the response of the biliary compartment of FLs to the various phases of OLT reliable markers are necessary. Previously we demonstrated that Alkaline Phosphatase was scarcely active in bile canaliculi of FLs and thus ruled it out as a marker. As an alternative, dipeptidylpeptidase-IV (DPP-IV, was investigated. This ecto-peptidase plays an important role in glucose metabolism, rapidly inactivating insulin secreting hormones (incretins that are important regulators of glucose metabolism. DPP-IV inhibitors are indeed used to treat Type II diabetes. Neuropeptides regulating bile transport and composition are further important substrates of DPP-IV in the enterohepatic axis. DPP-IV activity was investigated with an azo-coupling method in the liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. Protein expression was studied by immunofluorescence with the monoclonal antibody (clone 5E8. In Wistar rat liver, DPP-IV activity and expression were high in the whole biliary tree, and moderate in sinusoid endothelial cells, in agreement with the literature. Main substrates of DPP-IV in hepatocytes and cholangiocytes could be incretins GLP-1 and GIP, and neuropeptides such as vasoactive intestinal peptide (VIP and substance P, suggesting that these substances are inactivated or modified through the biliary route. In lean Zucker rat liver the enzyme reaction and protein expression patterns were similar to those of Wistar rat. In obese rat liver

PPARα agonists up-regulate organic cation transporters in rat liver cells

International Nuclear Information System (INIS)

Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

2006-01-01

It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

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V. Bertone

2011-02-01

Full Text Available Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT. Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS. However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20 that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but

Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme.

Science.gov (United States)

Bertone, V; Tarantola, E; Ferrigno, A; Gringeri, E; Barni, S; Vairetti, M; Freitas, I

2011-02-08

Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT). Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS). However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20) that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1), frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but most hepatocytes

The mechanisms underlying the hypolipidaemic effects of Grifola frondosa in the liver of rats

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Yinrun Ding

2016-08-01

Full Text Available The present study investigated the hypolipidaemic effects of Grifola frondosa and its regulation mechanism involved in lipid metabolism in liver of rats fed a high-cholesterol diet. The body weights and serum lipid levels of control rats, of hyperlipidaemic rats and of hyperlipidaemic rats treated with oral Grifola frondosa were determined. mRNA expression and concentration of key lipid metabolism enzymes were investigated. Serum cholesterol, triacylglycerol and low-density lipoprotein cholesterol levels were markedly decreased in hyperlipidaemic rats treated with Grifola frondosa compared with untreated hyperlipidaemic rats. mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR, acyl-coenzyme A: cholesterol acyltransferase (ACAT2, apolipoprotein B (ApoB, fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC1 were significantly down-regulated, while expression of cholesterol 7-alpha-hydroxylase (CYP7A1 was significantly up-regulated in the livers of treated rats compared with untreated hyperlipidaemic rats. The concentrations of these enzymes also paralleled the observed changes in mRNA expression. Two-dimensional polyacrylamide gel electrophoresis (2-DE and Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS were used to identify twenty proteins differentially expressed in livers of rats treated with Grifola frondosa compared with untreated hyperlipidemic rats. Of these twenty proteins, seven proteins were down-regulated and thirteen proteins were up-regulated. These findings indicate that the hypolipidaemic effects of Grifola frondosa reflected its modulation of key enzymes involved in cholesterol and triacylglycerol biosynthesis, absorption and catabolic pathways. Grifola frondosa may exert anti-atherosclerotic effects by inhibiting LDL oxidation through down-regulation and up-regulating proteins expression in the liver of rats. Therefore, Grifola frondosa may produce both hypolipidaemic

Food restriction modulates β-adrenergic-sensitive adenylate cyclase in rat liver during aging

International Nuclear Information System (INIS)

Katz, M.S.

1988-01-01

Adenylate cyclase activities were studied in rat liver during postmaturational aging of male Fischer 344 rats fed ad libitum or restricted to 60% of the ad libitum intake. Catecholamine-stimulated adenylate cyclase activity increased by 200-300% between 6 and 24-27 mo of age in ad libitum-fed rats, whereas in food-restricted rats catecholamine response increased by only 58-84% between 6 and 30 mo. In ad libitum-fed rats, glucagon-stimulated enzyme activity also increased by 40% between 6 and 12 mo and in restricted rats a similar age-related increase was delayed until 18 mo. β-Adrenergic receptor density increased by 50% between 6 and 24 mo in livers from ad libitum-fed but not food-restricted rats and showed a highly significant correlation with maximal isoproterenol-stimulated adenylate cyclase activity over the postmaturational life span. Age-related increases in unstimulated (basal) adenylate cyclase activity and nonreceptor-mediated enzyme activation were retarded by food restriction. The results demonstrate that food restriction diminishes a marked age-related increase in β-adrenergic-sensitive adenylate cyclase activity of rat liver. Alterations of adrenergic-responsive adenylate cyclase with age and the modulatory effects of food restriction appear to be mediated by changes in both receptor and nonreceptor components of adenylate cyclase

Effect of triiodothyronine on rat liver chromatin protein kinase

International Nuclear Information System (INIS)

Kruh, J.; Tichonicky, L.

1976-01-01

1) Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2) Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32 P when incubated with [γ- 32 P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32 P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins. (orig.) [de

Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

Science.gov (United States)

Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

2011-02-28

3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats

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Yavar Mahmoodzadeh

Full Text Available The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4.54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups, 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed.Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group.The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4. Keywords: Tanacetum parthenium, Carbon tetrachloride, Oxidative stress, Antioxidant enzymes, Liver damage

Renoprotective effect of crocin following liver ischemia/ reperfusion injury in Wistar rats

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Seyyed Ali Mard

2017-10-01

Full Text Available Objective(s: The objectives of the current study were to evaluate the effects of hepatic ‎ischemia/reperfusion (IR injury on the activity of antioxidant enzymes, biochemical factors, and ‎histopathological changes in rat kidney, and to investigate the effect of crocin on IR-‎related changes. Materials and Methods: Thirty-two male Wistar rats were randomly allocated into four groups (n=8. They were ‎sham-operated, IR, crocin pre-treatment, and crocin pretreatment+IR groups. Sham-operated ‎and Crocin pre-treatment groups received normal saline (N/S, 2 ml/day and crocin (200 mg/kg ‎for seven consecutive days intraperitoneally (IP, respectively, then rats underwent laparotomy, only. ‎IR and crocin pretreatment+IR groups received N/S and crocin with the same dose, time, and route, ‎respectively, then rats underwent partial (70% ischemia for 45 min that was followed by reperfusion ‎for 60 min. At the end of the experiment, kidney specimens were taken for histopathological and ‎antioxidant evaluations and also blood samples were obtained for biochemical analysis. Results: The results of the present study showed that crocin pre-treatment significantly increased ‎the activity of antioxidants, decreased the serum levels of liver enzymes and blood urea nitrogen ‎following IR-induced hepatic injury. Crocin also ameliorated kidney´s histopathological ‎disturbance beyond IR-induced hepatic injury. Conclusion: Crocin as an antioxidant agent protected renal insult following liver IR injury by ‎increasing the activity of antioxidant enzymes, reducing serum levels of liver enzymes, and ‎improving histopathological changes.‎

Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver.

Science.gov (United States)

Sadi, Gökhan; Bozan, Davut; Yildiz, Huseyin Bekir

2014-08-01

Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects, which might contribute to its usefulness in preventing complications associated with diabetes. The present study aimed to investigate resveratrol effects on catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression, their phosphorylation states and activities in rat liver of STZ-induced diabetes. Diabetes increased the levels of total protein phosphorylation and p-CAT, while mRNA expression, protein levels, and activity were reduced. Although diabetes induced transcriptional repression over GPx, it did not affect the protein levels and activity. When resveratrol was administered to diabetic rats, an increase in activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1 (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in nuclear factor kappa B (NFκB) gene expression in diabetes were associated with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism for reduced gene expression of antioxidant enzymes is proved to be nuclear translocation of redox-sensitive Nrf2 and NFκB in diabetes which is confirmed by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and NFκB. Taken together, these findings revealed that an increase in the oxidized state in diabetes intricately modified the cellular phosphorylation status and regulation of antioxidant enzymes. Gene regulation of antioxidant enzymes was accompanied by nuclear translocation of Nrf2 and NFκB. Resveratrol administration also activated a coordinated cytoprotective response against diabetes-induced changes in liver tissues.

Disturbances in lysosomal enzymes activity in rats, following experimental postradiation disease

International Nuclear Information System (INIS)

Drozdz, M.; Piwowarczyk, B.; Olczyk, K.; Pikula-Zachara, M.

1981-01-01

The studies were aimed at detecting the biological effects of radiation on rat's organism, through studying the activity of lysosomal enzymes in blood plasma and some organs. The contemporary studies suggest that lysosomes play an important role in the occurrence and course of postradiation disease. The obtained results suggest the multidirectional gamma-rays effects on lysosomal enzymes response in serum, leucocytes, liver lysosomes and in liver, kidneys, lungs, heart. Increased activity of acid phosphatase, beta-glucoronidase and beta-acetyl-glucosaminase in the tissues of irradiated animals indicates that gamma rays labilizate the lysosomal membrane. The range of changes indicates a selective nature of this phenomenon. Kidneys, lungs and liver appeared the most ray-sensitive organs. The activity of acid phosphatase was found to be most increased in blood serum and leucocytes. The activity of all examined enzymes in liver lysosomes was decreased. Acid phosphatase exhibited the greatest activity increases. Lysosomal responses are indicative of the degree of destructive or regenerative changes in the organism. (author)

A quantitative histochemical procedure for the demonstration of purine nucleoside phosphorylase activity in rat and human liver using Tetranitro BT and xanthine oxidase as auxiliary enzyme

NARCIS (Netherlands)

Frederiks, W. M.; Bosch, K. S.; van Gulik, T.

1993-01-01

A quantitative histochemical procedure was developed for the demonstration of purine nucleoside phosphorylase in rat liver using unfixed cryostat sections and the auxiliary enzyme xanthine oxidase. The optimum incubation medium contained 18% (w/v) poly(vinyl alcohol), 100 mM phosphate buffer, pH

Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats

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Balan Rajan

2015-06-01

Full Text Available Carvacrol is a main constituent in the essential oils of countless aromatic plants including Origanum Vulgare and Thymus vulgari, which has been assessed for substantial pharmacological properties. In recent years, notable research has been embarked on to establish the biological actions of Carvacrol for its promising use in clinical applications. The present study is an attempt to reveal the protective role of Carvacrol against N-Nitrosodiethylamine (DEN induced hepatic injury in male Wistar albino rats. DEN is an egregious toxin, present in numerous environmental factors, which enhances chemical driven liver damage by inducing oxidative stress and cellular injury. Administration of DEN (200 mg/kg bodyweight, I.P to rats results in elevated marker enzymes (in both serum and tissue. Carvacrol (15 mg/kg body weight suppressed the elevation of marker enzymes (in both serum and tissue and augmented the antioxidants levels. The hoisted activities of Phase I enzymes and inferior activities of Phase II enzymes were observed in DEN-administered animals, whereas Carvacrol treated animals showed improved near normal activity. Histological observations also support the protective role of Carvacrol against DEN induced liver damage. Final outcome from our findings intimate that Carvacrol might be beneficial in attenuating toxin induced liver damage.

The Effects of Space Flight on Some Liver Enzymes Concerned with Carbohydrate and Lipid Metabolism in Rats

Science.gov (United States)

Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

1978-01-01

The activities of about 30 enzymes concerned with carbohydrate and lipid metabolism and the levels of glycogen and of individual fatty acids were measured in livers of rats ex- posed to prolonged space flight (18.5 days) aboard COSMOS 986 Biosatellite. When flight stationary, (FS) and flight centrifuged (FC) rats were compared at recovery (R(sub 0)), decrceases in the activities of glycogen phosphorylase, alpha glycerphosphate, acyl transferase, diglyceride acyl transferase, acconitase and Epsilon-phosphogluconate dehydrogenase were noted in the weightless group (FS). The significance of these findings was strengthened since all activities, showing alterations at R(sub 0), returned to normal 25 days post-flight. Differences were also seen in levels of two liver constituents. When glycogen and total fatty acids of the two groups of flight animals were determined, differences that could be attributed to reduced gravity were observed, the FS group at R(sub 0) contained, on the average, more than twice the amount of glycogen than did controls ad a remarkable shift in the ratio of palmitate to palmitoleate were noted. These metabolic alterations appear to be unique to the weightless condition. Our data justify the conclusion that centrifugation during space flight is equivalent to terrestrial gravity.

Demonstration of glucose-6-phosphate dehydrogenase in rat Kupffer cells by a newly-developed ultrastructural enzyme-cytochemistry

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S Matsubara

2009-06-01

Full Text Available Although various tissue macrophages possess high glucose- 6-phosphate dehydrogenase (G6PD activity, which is reported to be closely associated with their phagocytotic/bactericidal function, the fine subcellular localization of this enzyme in liver resident macrophages (Kupffer cells has not been determined.We have investigated the subcellular localization of G6PD in Kupffer cells in rat liver, using a newly developed enzyme-cytochemical (copper-ferrocyanide method. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of Kupffer cells. Cytochemical controls ensured specific detection of the enzymatic activity. Rat Kupffer cells abundantly possessed enzyme-cytochemically detectable G6PD activity. Kupffer cell G6PD may play a role in liver defense by delivering NADPH to NADPH-dependent enzymes. G6PD enzyme-cytochemistry may be a useful tool for the study of Kupffer cell functions.

Effects of dibutyl phthalate on lipid metabolism and drug metabolising enzyme system in rats

International Nuclear Information System (INIS)

Arakaki, Mitsuo; Ariyoshi, Toshihiko.

1976-01-01

Effects of dibutyl phthalate (DBP) on the liver constituents and the drug metabolizing enzyme system were investigated in rats. 1. In the experiments at a single oral dose of DBP (630 or 1260 mg/kg), the glycogen content was decreased only at the high dose, but no effects were observed on the contents of glycogen, triglyceride, microsomal protein and cytochromes, and on the activities of drug metabolizing enzymes. 2. In the repeated oral dose of DBP (630 or 1260 mg/kg/day) for 5 days, the ratio of liver weight to body weight was increased in both female and male rats, whereas the increases of cytochrome P-450 content and aniline hydroxylase activity were noted only in male rats. However, the contents of liver triglyceride, phospholipids, and cholesterol were unchanged. On the other hand, serum cholesterol content which showed the tendency to be decreased at the low dose was significantly decreased at the high dose. 3. In the incorporation of 1- 14 C-acetate into liver and serum lipids after repeated oral dose of DBP (630 mg/kg/day) for 5 days in male rats, the incorporation into triglyceride showed tendency to be increased, whereas the incorporation into cholesterol and cholesterol ester remained unchanged in vivo and in vitro. (auth.)

The effect of steroidal contraceptives on liver enzymes and serum ...

African Journals Online (AJOL)

This study assessed the influence of steroidal contraceptives on liver enzymes and serum total protein using 48 adult female rats in four groups -A as control and B, C and D as tests. The animals were further divided into two subgroups - treatment (A1 - D1; n=6 each) and reversal (A2 - D2; n=6 each). Groups A1&A2 ...

Changes of α-glycerophosphate dehydrogenase activity in fatty liver of rats by amino acid imbalance

International Nuclear Information System (INIS)

Ogura, Masaji; Katsunuma, Eiichi; Akabane, Tomoko; Ogawa, Seiichi

1976-01-01

The previous study on the lipogenesis in the fatty livers of rats, which was induced by feeding the diet with imbalanced amino acid, revealed that the induction of this type of fatty livers was due mainly to the acceleration of triglyceride synthesis by the increase in both synthesis and esterification of fatty acid in the livers. Although many studies have been carried out on the dietary control of α-glycerophosphate dehydrogenase activity in rat livers, the enzyme change in amino acid imbalance has not been reported. In the present study, in order to elucidate the difference in the supply of glycerol moiety of triglyceride due to the imbalance, the change of the α-glycerophosphate dehydrogenase activity in livers was investigated. The experimental diets were 8% casein basal diet and basal + 0.3% DL-methionine imbalanced diet. 5 rats of each group were killed after 0.5 and 10 days on the diet, and the analysis of the lipid content in the livers and the determination of the α-glycerophosphate dehydrogenase activity were carried out. The linear response of the enzyme activity to time and protein concentration was obtained. The development of fatty livers was observed in the imbalanced diet group in the feeding period of 10 days. It was found that the specific activity of the imbalanced diet group increased significantly in 5 and 10 days as compared with that of the basal diet group. The elevation in the enzyme activity may suggest that the supply of α-glycerophosphate for triglyceride synthesis is also increased in this type of fatty livers. (Kako, I.)

Expression of liver-specific functions in rat hepatocytes following sublethal and lethal acetaminophen poisoning

DEFF Research Database (Denmark)

Tygstrup, N; Jensen, S A; Krog, B

1996-01-01

AIM: In order to study the short-term effect of moderate and severe reduction of liver function by acetaminophen poisoning of different severity on gene expression for liver-specific functions, rats were given 3.75 and 7.5 g per kg body weight acetaminophen intragastrically. The lower dose...... is associated with low mortality; after the higher dose, most rats die at between 12 and 24 h. METHODS: In the morning, 1 1/2, 3, 6, 9, and 12 h after the injection, the rats were killed and RNA was extracted from liver tissue. By slot-blot hybridization mRNA steady-state levels were determined for enzymes...

Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.

Science.gov (United States)

Menon, B Rajalakshmy; Rathi, M A; Thirumoorthi, L; Gopalakrishnan, V K

2010-10-01

The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity.

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

Science.gov (United States)

Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

2016-01-01

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

Acute effects of organotins on brain, liver and kidney in rats

Energy Technology Data Exchange (ETDEWEB)

Dwivedi, R.S.; Kaur, G.; Srivastava, R.C.; Srivastava, T.N.

1985-01-01

Effects of dioctyltin oxide (DOTO) tricyclohexyltin hydroxide (TCHTOH) and tributyltin oxide (TBTO) were examined on some enzymic activities in liver and kidney and biogenic amines level in brain of rats at 24 hours after single subcutaneous administration (25 ..mu..mole/100 g B. Wt.). All the organotin compounds produced a significant increase in the activity of alkaline phosphatase and adenosin triphosphatase and decrease in monoamine oxidase in both liver and kidney. DOTO and TCHTOH were more effective in impairing the activity of succinate dehydrogenase in liver. Concentrations of ..gamma..-aminobutyric acid (GABA) and dopamine were found to be significantly decreased in brain however, acetylcholine concentration remained unaltered. These results suggest that organotin compounds DOTO and TCHTOH are more toxic to rats than TBTO. 30 references, 3 tables.

Physiological covalent regulation of rat liver branched-chain alpha-ketoacid dehydrogenase

International Nuclear Information System (INIS)

Harris, R.A.; Powell, S.M.; Paxton, R.; Gillim, S.E.; Nagae, H.

1985-01-01

A radiochemical assay was developed for measuring branched-chain alpha-ketoacid dehydrogenase activity of Triton X-100 extracts of freeze-clamped rat liver. The proportion of active (dephosphorylated) enzyme was determined by measuring enzyme activities before and after activation of the complex with a broad-specificity phosphoprotein phosphatase. Hepatic branched-chain alpha-ketoacid dehydrogenase activity in normal male Wistar rats was 97% active but decreased to 33% active after 2 days on low-protein (8%) diet and to 13% active after 4 days on the same diet. Restricting protein intake of lean and obese female Zucker rats also caused inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex. Essentially all of the enzyme was in the active state in rats maintained for 14 days on either 30 or 50% protein diets. This was also the case for rats maintained on a commercial chow diet (minimum 23% protein). However, maintaining rats on 20, 8, and 0% protein diets decreased the percentage of the active form of the enzyme to 58, 10, and 7% of the total, respectively. Fasting of chow-fed rats for 48 h had no effect on the activity state of hepatic branched-chain alpha-ketoacid dehydrogenase, i.e., 93% of the enzyme remained in the active state compared to 97% for chow-fed rats. However, hepatic enzyme of rats maintained on 8% protein diet was 10% active before starvation and 83% active after 2 days of starvation. Thus, dietary protein deficiency results in inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex, presumably as a consequence of low hepatic levels of branched-chain alpha-ketoacids

Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital.

Science.gov (United States)

Furukawa, K; Numoto, S; Furuya, K; Furukawa, N T; Williams, G M

1985-10-01

The biochemical effects in the livers of male rats of prolonged administration of the experimental hepatocarcinogen nafenopin, a hypolipidemic agent and peroxisome proliferator, were compared to those of another experimental liver carcinogen, phenobarbital, which acts as a neoplasm promoter. Feeding of nafenopin, 0.03 mmol/kg basal diet for up to 24 weeks increased the numbers of hepatic peroxisomes, increased catalase activity, markedly decreased cytosolic glutathione transferase activities toward two substrates, decreased cytosolic glutathione peroxidase activities toward H2O2 and two organic peroxides, and suppressed the age-related increase in gamma-glutamyl transpeptidase activity. In contrast the livers of rats fed an equimolar concentration of phenobarbital displayed increases in cytosolic glutathione transferase activities and enhancement of gamma-glutamyl transpeptidase activity but no changes in glutathione peroxidase activities. There was also an enhancement of catalase activity without apparent increase in peroxisome number. Enzyme kinetic analyses revealed that the cytosolic glutathione transferase activities toward two halogenonitrobenzene substrates were inhibited in the rats fed nafenopin and displayed elevated Km and decreased Vmax. Kinetic studies of glutathione transferase activities in which nafenopin was mixed with normal rat liver cytosols in the assay system revealed competitive type inhibition toward 1-chloro-2,4-dinitrobenzene and a noncompetitive type of inhibition toward 3,4-dichloronitrobenzene. Likewise activities of glutathione peroxidases toward H2O2 and cumene hydroperoxide were suppressed by in vitro addition. Thus the effects of nafenopin and phenobarbital on liver biochemistry were very different. The inhibition of hepatic biotransformation and scavenger systems by nafenopin is suggested to be relevant to its hepatocarcinogenicity.

Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

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Azzouz I

2013-12-01

Full Text Available Inès Azzouz, Hamdi Trabelsi, Amel Hanini, Soumaya Ferchichi, Olfa Tebourbi, Mohsen Sakly, Hafedh AbdelmelekLaboratory of Integrative Physiology, Faculty of Sciences of Bizerte, Carthage University, TunisiaAbstract: The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip] in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip and selenium (0.20 mg/L, per os [by mouth] led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium to malondialdehyde level in rat liver.Keywords: nanocomplexes biosynthesis, antioxidative responses, X-ray diffraction, fluorescence microscopy, liver

The Use of Statin Substitutes to Improve the Lipid Profile in Liver Dysfunctional Male Albino Rats

International Nuclear Information System (INIS)

Amer, M.M.; Michael, M.I.

2010-01-01

More attention has been drawn to different strategies for prevention of cardiovascular associated with liver dysfunction. The aim of the present study is to compare between statin and free fat- milk supplemented with multivitamins in hyperlipidaemic male rats with or without liver dysfunction induced by CCl4. The animals were allocated to 7 equal experimental groups (16 rats each): control group, hypercholesterolemic group, hypercholestero-lemic-statin group, hypercholesterolemic-free fat milk-multivitamins group, hypercholesterolemic-CCl4 group, hypercholesterolemic-CCl4-statin group, and hypercholesterolemic-CCl4- fat-free milk-multivita-mins group. After one month half of the rats of each group were decapitated and the rest of the animals were decapitated after two months. Lipid profile, relative liver weight, liver function, CPK and LDH were determined. The effectiveness of statin drug in the management of blood lipids was confirmed without improving or worsening liver functions. Meanwhile, this effectiveness worsened in hypercholesterolemic rats treated with CCl4 as compared to hypercholesterolemic group. Administration of fat-free milk with multivitamins, as an alternative remedy for statin drug, has improved lipid profile in hypercholesterolemic rats and it revealed no changes in liver enzymes in hypercholesterolemic rats with liver dysfunction indicating the favorable use of them as hypolipotropic agent without affecting liver metabolism

Morphometric analysis of peroxisome proliferation by phthalate esters in rat liver

NARCIS (Netherlands)

Dormans JAMA; Jansen EHJM; de Vlugt-van den Koedijk FM; Riool-Nesselaar G

1992-01-01

Morphometric analysis was performed on liver sections of rats at light (LM) and electron microscopical (EM) level to demonstrate proliferation of peroxisomes after administration of di (2-ethylhexyl)phthalate at dietary levels of 0, 60, 200, 600, 2000 and 6000 mg/kg diet for 2 weeks. Enzyme

Monooxignase ensymic system of a liver of rats exposed to intravascular laser irradiation of blood

International Nuclear Information System (INIS)

Ibadova, G.A.

1997-01-01

Experimental study of the dynamic monooxidation of liver enzymic system was carried out on rats with experimental salmonellosis and the influence of the blood intravascular laser irradiation of blood on these enzymes was revealed. It was determined that by experimental salmonellosis oppression of the MOES activity of hepatocytes occurred. The blood intravascular irradiation by He-Ne laser promotes MOES oppression in rats suffered from salmonellosis. IVLIB as well as UV-laser show pronounced effect on the enzymes detoxication protection, mobilize their resistance to endogenic intoxication under the conditions of experimental salmonellosis. (author)

The effects of hydroalcoholic extract of Portulaca Oleracea on the serum concentreation of Hepatic enzymes in Rats

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Ali Zarei

2014-11-01

Full Text Available Background Hyperlipidemia can be cause a variety of diseases such as atherosclerosis, diabetes and fatty liver and subsequent liver enzyme increases. The Portulaca Oleracea plant has hypoglycemic and hypolipidemic properties. Therefore, in this study the effect of Portulca Oleracea herb extract on serum liver enzymes including aspartate aminotransferase (SGOT or AST, alanine aminotransferase (SGPT or ALT and alkaline phosphatase (ALP in rats were studied. Materials and Methods: In this experimental study, 60 Wistar rats were divided into 6 groups (n=10. Control group with normal diet, fat diet group and other groups, the experimental group received the same diet plus fat Portulaca oleracea extract maximum dose (800, the mean dose of (400, and a minimum dose of (200 mg / kg or intraperitoneally injection (ip and sort of Atorvastatin (10 mg kg. After the end of this period (21 days, blood sampling was performed and collected data were analyzed using the t and Tukey test, and SPSS software version 11.5. Results Comparison of statistical results indicated that alanine aminotransferase (ALT and Alkaline phosphatase (ALP increase in the control group that received only fatty foods, while the experimental groups received extract of Portulaca Oleracea, and groups receiving Atorvastatin had reduced levels of liver enzymes. Conclusion: Regarding hypoglycemic and hypolipidemic antioxidant activity of the extract and its effect on reducing liver enzymes, plant extracts can be recommended to improve liver function.

Effect of cadmium pretreatment on liver regeneration after partial hepatectomy in rats

International Nuclear Information System (INIS)

Margeli, A.; Theocharis, S.; Skaltsas, S.; Skopelitou, A.; Kittas, C.; Mykoniatis, M.; Varonos, D.

1994-01-01

In this study we examined the effect of cadmium pretreatment, administered 24 h before partial hepatectomy, on the liver regenerative process in rats, at different time intervals. The rate of 3 H thymidine incorporation into hepatic DNA and the activity of the enzyme thymidine kinase were used as indices of liver proliferative capacity. Thymidine kinase, the rate-determining enzyme of DNA biosynthesis, was suppressed during the first hours following partial hepatectomy in the liver of cadmium pretreated animals. DNA biosynthesis was also strongly decreased in cadmium pretreated animals, by delaying the first peak of liver regeneration, compared with the partially hepatectomized ones. Biochemical parameters, mitotic index and proliferating cell nuclear antigen staining were also coestimated. The above data suggest that cadmium pretreatment suppressed the hepatic regenerative process, probably due to the inhibition of thymidine kinase. (orig./MG)

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

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Mutiu Idowu Kazeem

2013-01-01

Full Text Available This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg diabetic rats significantly reduced (P<0.05 the fasting blood glucose compared to control groups. There was significant increase (P<0.05 in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase in the liver of the rats treated with it and significantly reduced (P<0.05 the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians.

Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.

Science.gov (United States)

Kabirifar, Razieh; Ghoreshi, Zohreh-Al-Sadat; Safari, Fatemeh; Karimollah, Alireza; Moradi, Ali; Eskandari-Nasab, Ebrahim

2017-02-01

Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model. We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively. Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (Pliver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.

In vitro biotransformation of flavonoids by rat liver microsomes

DEFF Research Database (Denmark)

Nielsen, S. E.; Breinholt, V.; Justesen, U.

1998-01-01

1. Sixteen naturally occurring flavonoids were investigated as substrates for cytochrome P450 in uninduced and Aroclor 1254-induced rat liver microsomes. Naringenin, hesperetin, chrysin, apigenin, tangeretin, kaempferol, galangin and tamarixetin were all metabolized extensively by induced rat liver...... pathway leading to the corresponding 3',4'-dihydroxylated flavonoids either by hydroxylation or demethylation. Structural requirements for microsomal hydroxylation appeared to be a single or no hydroxy group on the B-ring of the flavan nucleus. The presence of two or more hydroxy groups on the B......-ring seemed to prevent further hydroxylation. The results indicate that demethylation only occurs in the B-ring when the methoxy group is positioned at C-4'-, and not at the C-3'-position. 3. The CYP1A isozymes were found to be the main enzymes involved in flavonoid hydroxylation, whereas other cytochrome P...

Protective Effect of Urtica dioica on Liver Injury Induced By Hepatic Ischemia Reperfusion Injury in Rats

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Alpaslan TERZİ

2010-05-01

Full Text Available Background: This study was designed to investigate the effects of Urtica dioica on liverischemia reperfusion injury in rats. Methods: Thirty male Wistar-albino rats were used in this experimental study. Animals weredivided into three groups as sham operated (group 1, control (group 2, and Urtica dioicatreatment group (group 3. Urtica dioica 2ml/kg were administered intraperitoneally beforeischemia and immediately after the reperfusion. The levels of total antioxidant capacity, totalfree sulfidril group, Total oxidant status, Oxidative stress index, and myeloperoxidase in livertissues were measured. The serum levels of ALT, AST and LDH were also measuredResults: Total antioxidant capacity and total free sulfidril group in liver tissue were significantlyhigher in group 3 than in group 2. Oxidative stress index and myeloperoxidase in liver tissuewere significantly lower in group 3 than the group 2. The levels of liver enzymes in treatmentgroup were significantly lower than those in the control group. Histological tissue damage wasmilder in the treatment group than that in the control group.Conclusion: It is concluded that Urtica dioica increase the antioxidant capacity and decreaseoxidative stress and liver enzymes in the hepatic ischemi reperfusion injury of rats.

Studies on the postnatal development of the rat liver plasma membrane following maternal ethanol ingestion

Energy Technology Data Exchange (ETDEWEB)

Rovinski, B

1984-01-01

Studies on the developing rat liver and on the structure and function of the postnatal rat liver plasma membrane were carried out following maternal consumption of alcohol during pregnancy and lactation. A developmental study of alcohol dehydrogenase (ADH) indicated that both the activity and certain kinetic properties of the enzyme from the progeny of alcohol-fed and pair-fed mothers were similar. Fatty liver, however, developed in the alcoholic progeny only after ADH appeared on a day 19 of gestation. Further studies on structural and functional changes were then undertaken on the postnatal development of the rat liver plasma membrane. Radioligand binding studies performed using the hapatic alpha{sub 1}-adrenergic receptor as a plasma membrane probe demonstrated a significant decrease in receptor density in the alcoholic progeny, but no changes in binding affinity. Finally, the fatty acid composition of constituent phospholipids and the cholesterol content of rat liver plasma membranes were determined. All these observations suggest that membrane alterations in the newborn may be partially responsible for the deleterious action(s) of maternal alcoholism at the molecular level.

Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

Science.gov (United States)

Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

1990-01-01

To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

ENZYMOCHEMICAL AND BIOCHEMICAL CHANGES IN THE LIVER OF RATS INDUCED BY FURFURAL

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Dragana Veličković

2011-06-01

Full Text Available In today's industrial expansion of the chemical products, the liver is becoming increasingly important. Furfural (C4C3OCHO is a colorless liquid with pleasant aroma and it is partially soluble in water (8, 3% of weight. The elimination of furfural is done slowly through the kidneys and lungs, while the liver oxidizes it into pyromucic acid (C4C3OCOOH. Glucose-6-phosphate dehydrogenase (G6PD is a multi-component system of gluconeogenesis. Biochemical parameters (AST, ALT, glucose, γ-GT and alkaline phosphatase are important markers of liver damage.The aim of our study was to analyze the function of hepatocytes using biochemical parameters and to show the dynamics and topography in the development of changes in enzyme activity.The experiment was conducted on Wistar rats aged 6 weeks. The animals were divided into three groups. The control group received pure drinking water, the second group received a 50 mg/kg body weight (BW dose of furfural for seven days and in the third group the dose was progressively increased after which the animals were sacrificed. Biochemical methods were used to determine the parameters of liver damage. Enzyme-histochemical tests were performed on 8nm WKF 1150 cryostat cross sections which were stained according to Pearse (1968. The results are presented tables and graphs.The amount of enzymes and biochemical parameters in the control group were normal. In the group treated for 7 days, the activity of the enzymes was diffusely decreased while the biochemical parameters were increased. In the group of rats treated for 90 days, the periportal G6PD was constantly preserved. Biochemical parameters were different. The differences in all parameters were statistically significant (p<0.05 both in the group treated for 7 days and the group treated for 90 days. The same goes for the control group and the group treated for 7 days.Acute treatment with furfural causes damage to liver functions. The synthetic liver function is

Subcellular distribution of histone-degrading enzyme activities from rat liver

International Nuclear Information System (INIS)

Heinrich, P.C.; Raydt, G.; Puschendorf, B.; Jusic, M.

1976-01-01

Chromatin prepared from liver tissue contains a histone-degrading enzyme activity with a pH optimum of 7.5-8.0, whereas chromatin isolated from purified nuclei is devoid of it. The histone-degrading enzyme activity was assayed with radioactively labelled total histones from Ehrlich ascites tumor cells. Among the different subcellular fractions assayed, only lysosomes and mitochondria exhibited histone-degrading enzymes. A pH optimum around 4.0-5.0 was found for the lysosomal fraction, whereas 7.5-8.0 has been found for mitochondria. Binding studies of frozen and thawed lysosomes or mitochondria to proteinase-free chromatin demonstrate that the proteinase associated with chromatin isolated from frozen tissue originates from damaged mitochondria. The protein degradation patterns obtained after acrylamide gel electrophoresis are similar for the chromatin-associated and the mitochondrial proteinase and different from that obtained after incubation with lysosomes. The chromatin-associated proteinase as well as the mitochondrial proteinase are strongly inhibited by 1.0 mM phenylmethanesulfonyl fluoride. Weak inhibition is found for lysosomal proteinases at pH 5. Kallikrein-trypsin inhibitor, however, inhibits lysosomal proteinase activity and has no effect on either chromatin-associated or mitochondrial proteinases. The higher template activity of chromatin isolated from a total homogenate compared to chromatin prepared from nuclei may be due to the presence of this histone-degrading enzyme activity. (orig.) [de

Pathological effects of anabolic steroid (Sustanon® on liver of male rats

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E.R. Al-Kennany

2014-06-01

Full Text Available The present pathological study on the male rats aims to investigate the effects on liver tissue induced by repeated administration of three doses of sustanon for four periods. The experiment was done on the 100 adult male rats randomly divided into five groups 20 rats in each group. The first group is considered as a negative control treated with diet and water only. The second group is considered a positive control treated weekly for 60 days with sesame oil intramuscularly while groups III, IV and V treated with diluted sustanon in 5, 10 and 20 mg/kg body weight intramuscularly weekly for 60 days respectively. Blood was collected in a period 15, 30 and 60 days after treatment for measurements liver function tests ALT (alanine aminotransferase and AST (aspartate aminotransferas enzymes. Then the animals were dissected to take samples in a period 15, 30 and 60 days after treatment for histopathological examination, then 5 rats were lefted in each group in the diet and water for 30 days after last treatment for examination the above mentioned parameters. The results revealed the presence of significantly increasing of liver enzyme activation represented by ALT and AST at level P<0.05 compared with control groups. The value of these levels were higher in group V in a day 60 after treatment and its continue to increase even after stopping treatment and remained on diet and water only for 30 days. Pathologically, all treated groups with sustanon revealed gross and histopathological changes in liver tissue, there were enlargement and congestion gross. Histopathologically, the liver sections elucidate cellular swelling, vacuolar degeneration in the cytoplasm of hepatocytes in addition to fatty change and programmed cell death in all groups during a period 15, 30 and 60 days these changes continue even after stopping the treatment for 30 days but portal fibrosis has been observed.It has been concluded from this study that sustanon in concentration 5, 10

Liver insulinase and insulin-like activity of the blood plasma in irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Zhikhareva, A I; Dokshina, G A [Tomskij Gosudarstvennyj Univ. (USSR)

1975-05-01

Comparative quantitative analysis of the functional effect of radiation on the activity of liver insulinase of irradiated rats has shown that the insulinase activity of the blood plasma decreases (21-45%) one to three days after the exposure at betatron. Insulinase activity of the liver extracts is also inhibited (16-22%) as compared to intact liver extracts. Twelve days after the exposure and later, insulin-like activity of the plasma and the enzyme activity increase up to 37 per cent.

Developmental changes in rat liver branched-chain 2-oxo acid dehydrogenase.

OpenAIRE

May, E E; May, M E; Aftring, R P; Buse, M G

1982-01-01

Branched-chain 2-oxo acid dehydrogenase catalyses the first irreversible step in the degradation of the branched-chain amino acids leucine, isoleucine and valine. With specifically labelled 4-methyl-2-oxo[1-14C]pentanoate as substrate, the enzyme's activity was measured in rat liver homogenates. Activity (per g wet wL of liver or per mg of protein) increased most rapidly during the perinatal period (2 days before to 1 day after birth), reaching approximately adult values by the time of weanin...

Activities of xenobiotic metabolizing enzymes in rat placenta and liver in vitro

NARCIS (Netherlands)

Fabian, Eric; Wang, Xinyi; Engel, Franziska; Li, Hequn; Landsiedel, Robert; Ravenzwaay, van Bennard

2016-01-01

In order to assess whether the placental metabolism of xenobiotic compounds should be taken into consideration for physiologically-based toxicokinetic (PBTK) modelling, the activities of seven phase I and phase II enzymes have been quantified in the 18-day placenta of untreated Wistar rats. To

The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in type 2 diabetic rats.

Science.gov (United States)

Elattar, Samah; Estaphan, Suzanne; Mohamed, Enas A; Elzainy, Ahmed; Naguib, Mary

2017-10-01

There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH) 2 D3. Altered 1α,25(OH) 2 D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH) 2 D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH) 2 D3 (0.5μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH) 2 D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH) 2 D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH) 2 D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH) 2 D3 and metformin on liver in diabetic rats as

Protective effect of Sida cordata leaf extract against CCl(4) induced acute liver toxicity in rats.

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Mistry, Sunil; Dutt, K R; Jena, J

2013-04-13

To investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim. Wister albino rats were divided into 6 groups: Group I served as control; Group II served as hepatotoxic (CCl(4) treated) group; Group III, IV and V served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group VI served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies. Obtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl4 induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies. The results of this study strongly indicate the protective effect of SCLE against CCl(4) induced acute liver toxicity in rats and thereby scientifically support its traditional use. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Characteristics and significance of D-tagatose-induced liver enlargement in rats: An interpretative review.

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Bär, A

1999-04-01

This review addresses the issue of asymptomatic liver enlargement in rats. It was necessitated by the observation of significantly increased liver weights in rats fed diets with 10 to 20% D-tagatose, a potential new bulk sweetener, for between 28 and 90 days. Increases of liver size without accompanying histopathological changes or impairment of organ function have been observed in rats in response to the ingestion of various xenobiotic compounds (including some food additives), changes of dietary composition (e.g. , high doses of fructose and sucrose), metabolic aberrations (e.g., diabetes), as well as normal pregnancy and lactation. The underlying mechanism(s) are not yet understood in detail but peroxisome proliferation, microsomal enzyme induction, increased storage of glycogen or lipids, and hyperfunction due to an excessive workload are well-established causes of hepatomegaly in rats. In D-tagatose- and fructose-fed rats, a treatment-related increase of hepatic glycogen storage was identified as a likely cause of the liver enlargement. Dietary levels of 5% and about 15-20% were determined as no-effect levels (NOEL) for D-tagatose- and fructose-induced liver enlargement, respectively. At doses above the NOEL, D-tagatose is about four times more efficient than fructose in inducing liver enlargement. On the other hand, the estimated intake of D-tagatose from its intended uses in food is about four times lower than the actual fructose intake. Consequently, a similar safety margin would apply for both sugars. Considering the similarity of the liver effects in rats of fructose, a safe food ingredient, and D-tagatose, the absence of histopathological changes in rats fed a diet with 20% D-tagatose for 90 days, and the absence of adverse long-term consequences of glycogen-induced liver enlargement in rats, it is concluded that the observed liver enlargement in D-tagatose-fed rats has no relevance for the assessment of human safety of this substance. Copyright 1999

Livers from fasted rats acquire resistance to warm and cold ischemia injury.

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Sumimoto, R; Southard, J H; Belzer, F O

1993-04-01

Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

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Zeba Farooqui

Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

The Effects of Fenarimol and Methyl Parathion on Glucose 6-Phosphate Dehydrogenase Enzyme Activity in Rats

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Ferda ARI

2017-10-01

Full Text Available Fenarimol and methyl parathion are pesticides that have been used in agriculture for several years. These pesticides have significant effects on environmental and human health. Therefore, we investigated the effects of methyl parathion and fenarimol on glucose 6-phosphate dehydrogenase (EC 1.1.1.49 enzyme activity in rats. The glucose 6- phosphate dehydrogenase is the first enzyme of the pentose phosphate pathway and it is important in detoxifying reactions by NADPH generated. In this study, wistar albino rats administrated with methyl parathion (7 mg kg–1 and fenarimol (200 mg kg−1 by intraperitoneally for different periods (2, 4, 8, 16, 32, 64, and 72 h. The glucose 6-phosphate dehydrogenase enzyme activity was assayed in liver, kidney, brain, and small intestine in male and female rats. The exposure of fenarimol and methyl parathion caused increase of glucose 6-phosphate dehydrogenase enzyme activity in rat tissues, especially at last periods. We suggest that this increment of enzyme activity may be the reason of toxic effects of fenarimol and methyl parathion.

Transfer RNA methylases in rat placenta

International Nuclear Information System (INIS)

Jagtiani, S.K.; Narurkar, L.M.; Narurkar, M.V.

1977-01-01

Presence of tRNA methylases (5-adenosylmethionine : tRNA methyltransferases) was demonstrated at various stages of gestation in rat placenta, the enzyme being 50-100% higher than that of adult rat liver during early gestation. Placental tRNA methylases were shown to differ from those of liver in the extent of methylation. Glycine methyltransferase (S-adenosylmethionine : glycine methyltransferase), a regulatory enzyme in adult rat liver, was absent in placenta throughout gestation. The placental tRNA methylases could be inhibited in vitro by semipurified glycine methyltransferase from adult rat liver. The high placental tRNA methylase activity was comparable with the inhibitor-free enzyme activity of the adult rat liver. S-adenosyl-[Me- 14 C]-methionine was used in the investigation. (author)

Liver dysfunction following whole-body Co-60 irradiation in gerbil (Meriones hurrianae Jerdon) and house rat (Rattus rattus rufescens)

International Nuclear Information System (INIS)

Dixit, V.P.; Agrawal, M.; Gupta, C.

1976-01-01

Liver dysfunction following whole-body Co-60 irradiation has been studied in domestic and desert rat species. A significant elevation in the serum transaminases activity was noticed both in gerbil and house rat. Alkaline phosphatase and plasma cholesterol levels were also increased indicating an early radiation impairment of the liver tissue, which was later confirmed by histological studies. A steady fall in liver glycogen in irradiated gerbils was strikingly in contrast to an increase in irradiated house rat. Drastic depletion in liver glycogen, changes in the serum enzyme levels and the severity of the hepatic necrosis in gerbils point out that desert mammalian species are much more sensitive to radiation hazard as compared with domestic ones. (orig.) [de

The effect of streptozotocin-induced diabetes on phenylalanine hydroxylase expression in rat liver.

OpenAIRE

Taylor, D S; Dahl, H H; Mercer, J F; Green, A K; Fisher, M J

1989-01-01

The impact of experimentally induced diabetes on the expression of rat liver phenylalanine hydroxylase has been investigated. A significant elevation in maximal enzymic activity was observed in diabetes. This was associated with significant increases in the amount of enzyme, the phenylalanine hydroxylase-specific translational activity of hepatic RNA and the abundance of phenylalanine hydroxylase-specific mRNA. These changes in phenylalanine hydroxylase expression were not observed when diabe...

Effect of nutritional status on oxidative stress in an ex vivo perfused rat liver.

Science.gov (United States)

Stadler, Michaela; Nuyens, Vincent; Seidel, Laurence; Albert, Adelin; Boogaerts, Jean G

2005-11-01

Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers. Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies. Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats. In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.

Heterogeneous expression of cholesterol 7α-hydroxylase and sterol 27- hydroxylase genes in the rat liver lobulus

NARCIS (Netherlands)

Twisk, J.; Hoekman, M.F.M.; Mager, W.H.; Moorman, A.F.M.; Boer, P.A.J. de; Scheja, L.; Princen, H.M.G.; Gebhardt, R.

1995-01-01

We investigated the lobular localization and molecular level of expression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. Enzyme activity, mRNA, and gene

Cardamom powder supplementation prevents obesity, improves glucose intolerance, inflammation and oxidative stress in liver of high carbohydrate high fat diet induced obese rats.

Science.gov (United States)

Rahman, Md Mizanur; Alam, Mohammad Nazmul; Ulla, Anayt; Sumi, Farzana Akther; Subhan, Nusrat; Khan, Trisha; Sikder, Bishwajit; Hossain, Hemayet; Reza, Hasan Mahmud; Alam, Md Ashraful

2017-08-14

Cardamom is a well-known spice in Indian subcontinent, used in culinary and traditional medicine practices since ancient times. The current investigation was untaken to evaluate the potential benefit of cardamom powder supplementation in high carbohydrate high fat (HCHF) diet induced obese rats. Male Wistar rats (28 rats) were divided into four different groups such as Control, Control + cardamom, HCHF, HCHF + cardamom. High carbohydrate and high fat (HCHF) diet was prepared in our laboratory. Oral glucose tolerance test, organs wet weight measurements and oxidative stress parameters analysis as well as liver marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities were assayed on the tissues collected from the rats. Plasma lipids profiles were also measured in all groups of animals. Moreover, histological staining was also performed to evaluate inflammatory cells infiltration and fibrosis in liver. The current investigation showed that, HCHF diet feeding in rats developed glucose intolerance and increased peritoneal fat deposition compared to control rats. Cardamom powder supplementation improved the glucose intolerance significantly (p > 0.05) and prevented the abdominal fat deposition in HCHF diet fed rats. HCHF diet feeding in rats also developed dyslipidemia, increased fat deposition and inflammation in liver compared to control rats. Cardamom powder supplementation significantly prevented the rise of lipid parameters (p > 0.05) in HCHF diet fed rats. Histological assessments confirmed that HCHF diet increased the fat deposition and inflammatory cells infiltration in liver which was normalized by cardamom powder supplementation in HCHF diet fed rats. Furthermore, HCHF diet increased lipid peroxidation, decreased antioxidant enzymes activities and increased advanced protein oxidation product level significantly (p > 0.05) both in plasma and liver tissue which were modulated by

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

Science.gov (United States)

Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

1989-01-01

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

Protective Effect of Prosopis cineraria Against N-Nitrosodiethylamine Induced Liver Tumor by Modulating Membrane Bound Enzymes and Glycoproteins

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Naina Mohamed Pakkir Maideen

2012-06-01

Full Text Available Purpose: The objective of the present study was to evaluate the protective effect of methanol extract of Prosopis cineraria (MPC against N-nitrosodiethylamine (DEN, 200mg/kg induced Phenobarbital promoted experimental liver tumors in male Wistar rats. Methods: The rats were divided into four groups, each group consisting of six animals. Group 1 served as control animals. Liver tumor was induced in group 2, 3, and 4 and Group 3 animals received MPC 200mg/kg and Group 4 animals received MPC 400mg/kg. Results: Administration of DEN has brought down the levels of membrane bound enzymes like Na+/ K+ ATPase, Mg2+ ATPase and Ca2+ATPase which were later found to be increased by the administration of Prosopis cineraria (200 and 400mg/kg in dose dependent manner. The MPC extract also suppressed the levels of glycoproteins like Hexose, Hexosamine and Sialic acid when compared to liver tumor bearing animals. Conclusions: Our study suggests that MPC may extend its protective role by modulating the levels of membrane bound enzymes and suppressing glycoprotein levels.

The metabolism of L-phenylalanine and L-tyrosine by liver cells isolated from adrenalectomized rats and from streptozotocin-diabetic rats.

OpenAIRE

Stanley, J C; Fisher, M J; Pogson, C I

1985-01-01

Flux through, and maximal activities of, key enzymes of phenylalanine and tyrosine degradation were measured in liver cells prepared from adrenalectomized rats and from streptozotocin-diabetic rats. Adrenalectomy decreased the phenylalanine hydroxylase flux/activity ratio; this was restored by steroid treatment in vivo. Changes in the phosphorylation state of the hydroxylase may mediate these effects; there was no significant change in the maximal activity of the hydroxylase. Tyrosine metabol...

Effect of Aqueous Extract of Psidium Guajava Leaves on Liver Enzymes, Histological Integrity and Hematological Indices in Rats

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Uboh, Friday E.; Okon, Iniobong E.; Ekong, Moses B.

2010-01-01

Background Serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), albumin and total protein levels, as well as the tissue histological assay are known to be useful in assessing the functional integrity of the liver. Also, assessment of red and white blood cells count, hematocrit and hemoglobin concentrations is useful in determining the effect of some chemical substances on hemotopoietic system. In recent times, reports from medicinal plants research indicate that extracts from some plants are both hepatotoxic and hematotoxic, while others on the other hand are reported to be hepatoprotective and hematopoietic in action. This study considers the effects of aqueous extract of Psidium guajava (P. guajava) leaves on the histology and biochemical indices of liver function as well as hematological indices in rats. Methods In this study, phytochemical screening of the aqueous extract of P. guajava leaves was carried out. Also, male and female rats were administered with 200 mg/kg body weight oral daily doses of aqueous extract of P. guajava leaves for a period of 30 days. At the end of the administration period, the rats were anaesthesized with chloroform vapors and dissected for the collection of blood and liver tissues which were used for the hematopoietic and liver functions investigations. Results Preliminary phytochemical analysis of the plant leaves showed the presence of alkaloids, flavonoids, glycosides, polyphenols, reducing compounds, saponins and tannins. Liver function tests revealed that the serum ALT, AST and ALP, as well as the concentrations of total protein and albumin in male and female rats were not significantly (P > 0.05) affected by the oral administration of the extract. Histopathological study also did not show any adverse alteration in the morphological architecture of the liver tissues in both sexes of the animal model. However, red blood cell counts, hemotocrit and hemoglobin concentrations increased

HYPOLIPIDEMIC EFFECT OF CURCUMIN OR CO-ENZYME Q1-0 AND THEIR MIXTURE ON OBESE RATS FED A HIGH CHOLESTEROL DIET

International Nuclear Information System (INIS)

SHAHIN, M.I.M.

2008-01-01

In the current study, hyperlipidemia was induced in the rats by feeding diet enriched with cholesterol for two weeks. After 2 weeks of induction of hypercholesterolemia in rats and in comparison to normal rats, the results showed that incorporation of extra cholesterol in diet led to significant increases in serum cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, leptin and MDA levels. On the other hand, total serum triiodothyronine (T3), liver glutathione (GSH) and glutathione peroxidase (GPx) activities were decreased significantly in cholesterol fed rats. The concentration of TBARS in the liver was elevated.All previous parameters were corrected after the hypercholesterolemic rats were treated with curcumin or co-enzyme Q 1 -0 or a mixture of them dependent on the time of treatment. These findings are consistent with the concept that curcumin and co-enzyme Q 10 are antioxidant agents. The underlying mechanisms of these effects were discussed

Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa.

Science.gov (United States)

Zeng, Huawei; Yan, Lin; Cheng, Wen-Hsing; Uthus, Eric O

2011-08-01

The regulation of site-specific DNA methylation of tumor suppressor genes has been considered as a leading mechanism by which certain nutrients exert their anticancer property. This study was to investigate whether selenium (Se) affects the methylation of globe genomic DNA and the exon-specific p53 gene. Three groups of rats (n = 6-7/group) were fed the AIN-93G basal diet supplemented with 0 [Se deficient (D)], 0.15 [Se adequate (A)], or 4 mg [Se supranutritional (S)] (Se as l-selenomethionine)/kg diet for 104 d, respectively. Rats fed the A or S diet had greater plasma and liver glutathione peroxidase activity, liver thioredoxin reductase activity, and plasma homocysteine concentration than those fed the D diet. However, compared with the A diet, rats fed the S diet did not further increase these Se-dependent enzyme activities or homocysteine concentration. In contrast, Se concentrations in kidney, liver, gastrocnemius muscle, and plasma were increased in a Se-dose-dependent manner. Interestingly, rats fed the S diet had significantly less global liver genomic DNA methylation than those fed the D diet. However, the S diet significantly increased the methylation of the p53 gene (exons 5-8) but not the β-actin gene (exons 2-3) DNA in liver and colon mucosa compared with those fed the D diet. Taken together, long-term Se consumption not only affects selenoprotein enzyme activities, homocysteine, tissue Se concentrations, and global genomic DNA methylation but also increases exon-specific DNA methylation of the p53 gene in a Se-dose-dependent manner in rat liver and colon mucosa.

Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

Science.gov (United States)

Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

2015-01-01

Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.

Science.gov (United States)

Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan

2008-01-01

To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (pliver disease are warranted.

Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats.

Science.gov (United States)

Ziamajidi, Nasrin; Behrouj, Hamid; Abbasalipourkabir, Roghayeh; Lotfi, Fatemeh

2018-04-01

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.

Mechanistic studies with solubilized rat liver steroid 5 alpha-reductase: Elucidation of the kinetic mechanism

International Nuclear Information System (INIS)

Levy, M.A.; Brandt, M.; Greway, A.T.

1990-01-01

A solubilized preparation of steroid 5 alpha-reductase from rat liver has been used in studies focused toward an understanding of the kinetic mechanism associated with enzyme catalysis. From the results of analyses with product and dead-end inhibitors, a preferentially ordered binding of substrates and release of products from the surface of the enzyme is proposed. The observations from these experiments were identical with those using the steroid 5 alpha-reductase activity associated with rat liver microsomes. The primary isotope effects on steady-state kinetic parameters when [4S-2H]NADPH was used also were consistent with an ordered kinetic mechanism. Normal isotope effects were observed for all three kinetic parameters (Vm/Km for both testosterone and NADPH and Vm) at all substrate concentrations used experimentally. Upon extrapolation to infinite concentration of testosterone, the isotope effect on Vm/Km for NADPH approached unity, indicating that the nicotinamide dinucleotide phosphate is the first substrate binding to and the second product released from the enzyme. The isotope effects on Vm/Km for testosterone at infinite concentration of cofactor and on Vm were 3.8 +/- 0.5 and 3.3 +/- 0.4, respectively. Data from the pH profiles of these three steady-state parameters and the inhibition constants (1/Ki) of competitive inhibitors versus both substrates indicate that the binding of nicotinamide dinucleotide phosphate involves coordination of its anionic 2'-phosphate to a protonated enzyme-associated base with an apparent pK near 8.0. From these results, relative limits have been placed on several of the internal rate constants used to describe the ordered mechanism of the rat liver steroid 5 alpha-reductase

Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with α-Naphthylisothiocyanate

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Tadashi Nakamura

2013-01-01

Full Text Available We examined the protective effect of Brazilian propolis against liver damage with cholestasis in rats treated with α-naphthylisothiocyanate (ANIT in comparison with that of vitamin E (VE. Rats orally received Brazilian propolis ethanol extract (BPEE (25, 50, or 100 mg/kg, VE (250 mg/kg or vehicle at 12 h after intraperitoneal injection of ANIT (75 mg/kg and were killed 24 h after the injection. Vehicle-treated rats showed liver cell damage and cholestasis, judging from the levels of serum marker enzymes and components. The vehicle group had increased serum total cholesterol, triglyceride, phospholipid, and lipid peroxide levels, increased hepatic lipid peroxide, reduced glutathione, and ascorbic acid levels and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. BPEE (50 mg/kg administered to ANIT-treated rats prevented liver cell damage and cholestasis and attenuated these serum and hepatic biochemical changes except hepatic ascorbic acid, although administered BPEE (25 or 100 mg/kg was less effective. VE administered to ANIT-treated rats prevented liver cell damage, but not cholestasis, and attenuated increased serum lipid peroxide level, increased hepatic lipid peroxide level and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. These results indicate that BPEE protects against ANIT-induced liver damage with cholestasis in rats more effectively than VE.

Conversion of L-thyroxine to L-triiodothyronine in the rat liver under in vitro conditions

International Nuclear Information System (INIS)

Nauman, A.; Kaminski, T.; Pastuszko, D.

1979-01-01

Conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ) has been studied in liver homogenates obtained from normal and hypothyroid rats. Liver homogenates were incubated for 0-60 minutes at 37 0 C in Tris buffer containing sucrose and T 4 , pH 7.4. T 3 generated during incubation was measured by a specific radioimmunoassay of an ethanol extract of the incubates. Conversion rate of T 4 to T 3 by liver homogenates from intact rats was found to be time, protein concentration and substrate concentration (T 4 ) dependent. Heating of homogenate above 60 0 C abolished while cooling significantly decreased the monodeiodination. In homogenates from hypothyroid rats the conversion and its rate were significantly decreased. The results of present study confirmed enzymatic character of monodeiodination reaction. Decreased conversion of T 4 to T 3 in hypothyroidism suggests that biosynthesis of converting enzyme may be regulated by thyroid hormones. (author)

Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

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Bauyrzhan Umbayev

2014-12-01

Full Text Available Introduction: The possible alternative approach to whole-organ transplantation is a cell-based therapy, which can also be used as a "bridge" to liver transplantation.  However, morphological and functional changes in the liver of patients suffering from chronic liver fibrosis and cirrhosis restrict the effectiveness of direct cell transplantation. Therefore, extra hepatic sites for cell transplantation, including the spleen, pancreas, peritoneal cavity, and subrenal capsule, could be a useful therapeutic approach for compensation of liver functions. However, a method of transplantation of hepatocytes into ectopic sites is needed to improve hepatocyte engraftment. Previously published data has demonstrated that mouse lymph nodes can support the engraftment and proliferation of hepatocytes as ES and rescue Fah mice from lethal liver failure. Thus, the aim of the study was to evaluate the engraftment of i.p. injected allogeneic hepatocytes into extra hepatic sites in albino rats with chemically induced liver fibrosis (LF. Materials and methods: Albino rats were randomly divided into 4 groups: (1 intact group (n = 18; (2 rats with induced LF (n = 18; (3 rats with induced LF and transplanted with hepatocytes (n = 18; (4 as a control, rats were treated with cyclosporine A only (n = 18. In order to prevent an immune response, groups 2 and 3 were subjected to immunosuppression by cyclosporine A (25 mg/kg per day. LF was induced using N-nitrosodimethylamine (NDMA, i.p., 10 mg/kg, three times a week for 4 weeks and confirmed by histological analysis of the liver samples. Hepatocytes transplantation (HT was performed two days after NDMA exposure cessation by i.p. injection of 5×106 freshly isolated allogeneic hepatocytes. Liver function was assessed by quantifying blood biochemical parameters (ALT, AST, GGT, total protein, bilirubin, and albumin at 1 week, 1 month, and 2 months after hepatocytes transplantation (HT. To confirm a hepatocytes�

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

International Nuclear Information System (INIS)

Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M.; Ahr, Hans-Juergen; Schmidt, Ulrich; Enzmann, Harald H.

2004-01-01

Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using 32 P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had 32 P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

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Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

2004-10-01

Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

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Daleya Abdulaziz Bardi

Full Text Available This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg or ELAP (250 or 500 mg/kg. Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed

Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

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Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

2014-01-01

This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from

PASS-Predicted Hepatoprotective Activity of Caesalpinia sappan in Thioacetamide-Induced Liver Fibrosis in Rats

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Farkaad A. Kadir

2014-01-01

Full Text Available The antifibrotic effects of traditional medicinal herb Caesalpinia sappan (CS extract on liver fibrosis induced by thioacetamide (TAA and the expression of transforming growth factor β1 (TGF-β1, α-smooth muscle actin (αSMA, and proliferating cell nuclear antigen (PCNA in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY, and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson’s trichrome staining, immunohistochemical analysis, and western blotting. In vivo determination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1, and matrix metalloproteinases (MPPS was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1, αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.

The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

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Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

2017-04-04

The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

Alanine metabolism in pyridoxine-depleted rat liver

International Nuclear Information System (INIS)

Okada, Mitsuko; Abe, Midori

1976-01-01

Alanine metabolism in normal and pyridoxine-deficient rats was studied in vivo and in vitro. Incorporation of 14 C-alanine into various liver components was determined and no difference was shown between normal and deficient animals in the incorporation into liver homogenates, lipid, protein and plasma glucose. Using the liver slice system, gluconeogenic activity from alanine or pyruvate was 40% lower in deficient rats compared with the activity of normal rats. However, inhibition was completely removed by the addition of 2-oxoglutarate to alanine. Penicillamine did not affect glucose formation from alanine in the liver slice. (auth.)

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats.

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Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

2013-01-01

This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians.

[L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

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Kopyl'chuk, G P; Buchkovskaia, I M

2014-01-01

The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats

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Chien-Chun Li

2018-01-01

Full Text Available The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg and 400 LO (400 mg/kg and its major component, citral (240 mg/kg, on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(PH:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5′-diphospho (UDP glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen.

Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats.

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Nagao, Hidenori; Sasaki, Makoto; Imazu, Tetsuya; Takahashi, Kenjo; Aoki, Hironori; Minato, Kouichi

2014-10-29

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T4). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T4 turnover. We compared serum T4 turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T3). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T3 infusion. After the T3 infusion, the turnover rate of serum T4 in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T3 infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T3 infusion. This study suggests that repression of the disappearance of serum T4 in rats after Tx is a homeostatic response to decreased serum T3 concentrations. Additionally, T4 glucuronide is a storage form of T4, but may also have biological significance. These results suggest strongly that repression of deiodination of T4 by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

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Maurya, Brajesh Kumar; Trigun, Surendra Kumar

2016-01-01

Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis. PMID:26682000

HBK-14 and HBK-15 Do Not Influence Blood Pressure, Lipid Profile, Glucose Level, or Liver Enzymes Activity after Chronic Treatment in Rats.

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Pytka, Karolina; Głuch-Lutwin, Monika; Knutelska, Joanna; Jakubczyk, Magdalena; Waszkielewicz, Anna; Kotańska, Magdalena

2016-01-01

Older and even new antidepressants cause adverse effects, such as orthostatic hypotension, hyper- or hypoglycemia, liver injury or lipid disorders. In our previous experiments we showed significant antidepressant- and anxiolytic-like activities of dual 5-HT1A and 5-HT7 antagonists with α1-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15). Here, we evaluated the influence of chronic administration of HBK-14 and HBK-15 on blood pressure (non-invasive blood pressure measurement system for rodents), lipid profile (total cholesterol, low density lipoproteins-LDL, high density lipoproteins-HDL, triglycerides), glucose level, and liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase). We determined potential antihistaminic (isolated guinea pig ileum) and antioxidant properties (ferric reducing ability of plasma-FRAP, non-protein thiols-NPSH, stable free radical diphenylpicrylhydrazyl-DPPH) cytotoxicity. Our experiments revealed that HBK-14 and HBK-15 did not influence blood pressure, lipid profile, glucose level or liver enzymes activity in rats after 2-week treatment. We also showed that none of the compounds possessed antioxidant or cytotoxic properties at antidepressant- and anxiolytic-like doses. HBK-14 and HBK-15 very weakly blocked H1 receptors in guinea pig ileum. Positive results of our preliminary experiments on the safety of HBK-14 and HBK-15 encourage further studies concerning their effectiveness in the treatment of depression and/or anxiety disorders.

HBK-14 and HBK-15 Do Not Influence Blood Pressure, Lipid Profile, Glucose Level, or Liver Enzymes Activity after Chronic Treatment in Rats.

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Karolina Pytka

Full Text Available Older and even new antidepressants cause adverse effects, such as orthostatic hypotension, hyper- or hypoglycemia, liver injury or lipid disorders. In our previous experiments we showed significant antidepressant- and anxiolytic-like activities of dual 5-HT1A and 5-HT7 antagonists with α1-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxyethoxyethyl]-4-(2-methoxyphenylpiperazine hydrochloride (HBK-14 and 1-[(2-chloro-6-methylphenoxyethoxyethyl]-4-(2-methoxyphenylpiperazine hydrochloride (HBK-15. Here, we evaluated the influence of chronic administration of HBK-14 and HBK-15 on blood pressure (non-invasive blood pressure measurement system for rodents, lipid profile (total cholesterol, low density lipoproteins-LDL, high density lipoproteins-HDL, triglycerides, glucose level, and liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase. We determined potential antihistaminic (isolated guinea pig ileum and antioxidant properties (ferric reducing ability of plasma-FRAP, non-protein thiols-NPSH, stable free radical diphenylpicrylhydrazyl-DPPH cytotoxicity. Our experiments revealed that HBK-14 and HBK-15 did not influence blood pressure, lipid profile, glucose level or liver enzymes activity in rats after 2-week treatment. We also showed that none of the compounds possessed antioxidant or cytotoxic properties at antidepressant- and anxiolytic-like doses. HBK-14 and HBK-15 very weakly blocked H1 receptors in guinea pig ileum. Positive results of our preliminary experiments on the safety of HBK-14 and HBK-15 encourage further studies concerning their effectiveness in the treatment of depression and/or anxiety disorders.

Photoaffinity labeling of steroid 5 alpha-reductase of rat liver and prostate microsomes

International Nuclear Information System (INIS)

Liang, T.; Cheung, A.H.; Reynolds, G.F.; Rasmusson, G.H.

1985-01-01

21-Diazo-4-methyl-4-aza-5 alpha-pregnane-3,20-dione (Diazo-MAPD) inhibits steroid 5 alpha-reductase in liver microsomes of female rats with a K/sub i/ value of 8.7 +/- 1.7 nM, and the inhibition is competitive with testosterone. It also inhibits the binding of a 5 alpha-reductase inhibitor, [ 3 H] 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([ 3 H]4-MA), to the enzyme in liver microsomes. The inhibition of 5 alpha-reductase activity and of inhibitor binding activity by diazo-MAPD becomes irreversible upon UV irradiation. [1,2- 3 H]Diazo-MAPD binds to a single high affinity site in liver microsomes of female rats, and this binding requires NADPH. Without UV irradiation, this binding is reversible, and it becomes irreversible upon UV irradiation. Both the initial reversible binding and the subsequent irreversible conjugation after UV irradiation are inhibited by inhibitors (diazo-MAPD and 4-MA) and substrates (progesterone and testosterone) of 5 alpha-reductase, but they are not inhibited by 5 alpha-reduced steroids. Photoaffinity labeled liver microsomes of female rats were solubilized and fractionated by high performance gel filtration. The radioactive conjugate eluted in one major peak at Mr 50,000

Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats.

Science.gov (United States)

Li, Chien-Chun; Yu, Hsiang-Fu; Chang, Chun-Hua; Liu, Yun-Ta; Yao, Hsien-Tsung

2018-01-01

The essential oil from a lemongrass variety of Cymbopogon flexuosus [lemongrass oil (LO)] is used in various food and aroma industry products and exhibits biological activities, such as anticancer and antimicrobial activities. To investigate the effects of 200 LO (200 mg/kg) and 400 LO (400 mg/kg) and its major component, citral (240 mg/kg), on drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in the liver, male Sprague-Dawley rats were fed a pelleted diet and administered LO or citral by gavage for 2 weeks. After 2 weeks of feeding, the effects of LO and citral on the metabolism and toxicity of acetaminophen were determined. The results showed that rats treated with 400 LO or citral had significantly reduced hepatic testosterone 6β-hydroxylation and ethoxyresorufin O-deethylation activities. In addition, NAD(P)H:quinone oxidoreductase 1 activity was significantly increased by citral, and Uridine 5'-diphospho (UDP) glucurosyltransferase activity was significantly increased by 400 LO in the rat liver. Treatment with 400 LO or citral reduced lipid peroxidation and reactive oxygen species levels in the liver. After acetaminophen treatment, however, LO and citral treatment resulted in little or no change in plasma alanine aminotransferase activity and acetaminophen-protein adducts content in the liver. Our results indicate that LO and citral may change the activities of drug-metabolizing enzymes and reduce oxidative stress in the liver. However, LO and citral may not affect the detoxification of acetaminophen. Copyright © 2017. Published by Elsevier B.V.

Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

Science.gov (United States)

El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

2016-12-01

Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

Evaluating correlation between serum liver enzymes and toxocariasis: a case control study

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Hosein Miladi

2016-06-01

Full Text Available Objective: To evaluate the prevalence of toxocariasis in individuals with the normal and abnormal level of liver enzymes. Methods: In this case-control study, the serum samples were collected in the individuals referred to diagnostic laboratories of Arak in Iran. A total of 144 sera with abnormal level of liver enzymes were selected as cases and the same numbers of sera with the normal level of liver enzymes also were selected as controls. The sera were examined for anti-Toxocara IgG. Results: Twelve (4.2% sera contained anti-Toxocara antibody and all of them were in the case group. Although the mean of all liver enzymes was significantly different in the two groups (P < 0.05, statistical test showed no relationship between the level of liver enzymes and toxocariasis. Conclusions: It was concluded that the liver enzyme alteration is not the valid indicator for predicting toxocariasis. Because the kind of liver dysfunction, that is caused by the larvae of Toxocara, is unspecified, and it seems factors such as the number of larvae can play a basic role for the emergence of alterations.

Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

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Brajesh Kumar Maurya

2016-01-01

Full Text Available Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1 induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis.

Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.

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Rouas, Caroline; Souidi, Maâmar; Grandcolas, Line; Grison, Stephane; Baudelin, Cedric; Gourmelon, Patrick; Pallardy, Marc; Gueguen, Yann

2009-11-01

The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. Copyright © 2009 Elsevier B.V. All rights reserved.

Gamma radiation induced alterations in the ultrastructure of pancreatic islet, metabolism and enzymes in wistar rat

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Daoo, J.V.; Suryawanshi, S.A. [Inst. of Science, Bombay (India)

1992-07-01

Effects of gamma irradiation (600 rads) on the ultrastructure of pancreatic islet, metabolism and some enzymes in wistar rat, are reported. Electron microscopic observations of endocrine pancreas revealed prominent changes in beta cells while alpha and delta cells were not much affected. Irradiation also inflicted hyperglycemia, increase in liver and muscle glycogen and decrease in insulin level. It has also increased the activity of enzymes but failed to produce significant changes in protein, lipid and mineral metabolism. (auth0008.

Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

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Maryam Salehi

2016-02-01

Full Text Available Background Diazinon (DZN is one of the most organophosphates that widely used in agriculture and ectoparasiticide formulations. Its extensive use as an effective pesticide was associated with the environmental deleterious effects on biological systems. Objectives The aim of this study was to investigate the potency of DZN to affect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into control and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentrations, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxidative stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the effect of DZN on liver antioxidant system was more than kidney.

Pre-existing liver cirrhosis reduced the toxic effect of diethylene glycol in a rat model due to the impaired hepatic alcohol dehydrogenase.

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Ming Xing Huang; Xiao Mou Peng; Lin Gu; Gui Hua Chen

2011-09-01

Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were intraperitoneally administered a single dose of DEG, and randomly killed 1, 2, 5 or 8 days following exposure. Compared with control rats, the model rats had significantly higher blood CO(2)-combining power, lower blood urine nitrogen, serum creatinine and alanine aminotransferase levels on the second day and a lower mortality rate on the eighth day following DEG exposure. Enlargements of liver and kidneys and degeneration and necrosis of hepatocytes and renal tubules in the model rats was also less serious than in the control rats. Urine DEG levels were significantly higher on the first day in the model rats than the control rats (46.65 ± 8.79 mg vs 18.88 ± 6.18 mg, p activity in the model rats was significantly lower than that in the control rats, which was positively related to renal damage. The toxic effects of DEG in rats with pre-existing liver cirrhosis are significantly reduced, which may be due to the decreased hepatic ADH activity. It suggests that the metabolite of ADH is responsible for DEG poisoning, and this toxic metabolite may mainly originate in the liver.

The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

International Nuclear Information System (INIS)

Al-Damegh, Mona Abdalla

2007-01-01

Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

Importance Rat Liver Morphology and Vasculature in Surgical Research.

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Vdoviaková, Katarína; Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej

2016-12-02

BACKGROUND The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. MATERIAL AND METHODS Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. RESULTS We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. CONCLUSIONS Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.

Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc

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Medici, Valentina; Sturniolo, Giacomo Carlo; D' Inca, Renata [Department of Surgical and Gastroenterological Sciences, University of Padua, Padua (Italy); Santon, Alessandro; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola [Department of Biology, University of Padua, via U. Bassi 58/B, 35131 Padua (Italy)

2002-09-01

The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh{sup 8}dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week. (orig.)

Hepatoprotective effect of Ginkgoselect Phytosome in rifampicin induced liver injury in rats: evidence of antioxidant activity.

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Naik, Suresh R; Panda, Vandana S

2008-09-01

The protective effects of Ginkgoselect Phytosome (GBP) on Rifampicin (RMP) induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. Liver damage was induced in Wistar rats by administering rifampicin (500 mg/kg, p.o.) daily for 30 days. Simultaneously, GBP at 25 mg/kg and 50 mg/kg, and the reference drug silymarin (100 mg/kg) were administered orally for 30 days/daily to RMP treated rats. Levels of marker enzymes (SGOT, SGPT and SALP), albaumin (Alb) and total proteins (TP) were assessed in serum. The effects of GBP on lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were assayed in liver homogenates to evaluate antioxidant activity. GBP (25 and 50 mg/kg) and silymarin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose dependant manner. The present findings suggest that the hepatoprotective effect of GBP in RMP induced oxidative damage may be related to its antioxidant and free radical scavenging activity.

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

Science.gov (United States)

Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

1999-04-01

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

NARCIS (Netherlands)

STEEN, H; MEIJER, DKF; Merema, M.T.

The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation

Homology analyses of the protein sequences of fatty acid synthases from chicken liver, rat mammary gland, and yeast

International Nuclear Information System (INIS)

Chang, Soo-Ik; Hammes, G.G.

1989-01-01

Homology analyses of the protein sequences of chicken liver and rat mammary gland fatty acid synthases were carried out. The amino acid sequences of the chicken and rat enzymes are 67% identical. If conservative substitutions are allowed, 78% of the amino acids are matched. A region of low homologies exists between the functional domains, in particular around amino acid residues 1059-1264 of the chicken enzyme. Homologies between the active sites of chicken and rat and of chicken and yeast enzymes have been analyzed by an alignment method. A high degree of homology exists between the active sites of the chicken and rat enzymes. However, the chicken and yeast enzymes show a lower degree of homology. The DADPH-binding dinucleotide folds of the β-ketoacyl reductase and the enoyl reductase sites were identified by comparison with a known consensus sequence for the DADP- and FAD-binding dinucleotide folds. The active sites of all of the enzymes are primarily in hydrophobic regions of the protein. This study suggests that the genes for the functional domains of fatty acid synthase were originally separated, and these genes were connected to each other by using different connecting nucleotide sequences in different species. An alternative explanation for the differences in rat and chicken is a common ancestry and mutations in the joining regions during evolution

Synchrotron Based Phase Contrast Tomography of Hyper cholesteromic Rat Liver

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Fatima A

2017-05-01

Full Text Available X-ray phase contrast imaging technique has been applied for the study of morphological variations in soft tissues. The effect of an antioxidant, α-lipoic acid in reducing hypercholesterolemia in rats is investigated. The experiment was conducted to measure serum lipid profile and diameter of vessels in rat liver, as liver is the most vital organ in hypolipidemic activity studies. Methods: Four groups of male Wistar rats, control (Group I, hyperlipidemic (Group II, positive control (Group III and treated Group IV were studied for serum lipid profile and liver vessels with synchrotron X-ray phase tomography. The Group I rats received chow diet, in Group II rats, administration of 20% butter rich diet induced hyperlipidemia. Group III, treated rats received hypolipidemic drug Atorvastatin and Group IV animals received a potent antioxidant DL-α-Lipoic acid. The excised liver tissue immersed in 10% formalin. X-ray phase contrast tomography was performed for comparison of diameter of liver vessels. Results: Among the four group of animals, the diameter of liver vessels was much larger in hypercholesterolemic rat (Group II. The liver vessel diameter comparison with X-ray phase contrast tomography and the lipid profile shows reduction in serum lipids and lipoproteins by ALA treatment.

Sex-dependent differences in phenobarbitane-induced oestradiol-2-hydroxylase activity in rat liver

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Theron, C.N.; Neethling, A.C.; Taljaard, J.J.F. (Stellenbosch Univ. (South Africa). Dept. of Chemical Pathology)

1981-08-15

Oestradiol-2-hydroxylase (E/sub 2/-OH) activity was measured in liver and brain microsomes of 6-8-week-old Wistar rats. Phenobarbitone (75 mg/kg daily for 3 days) significantly increased enzyme activity in the liver of males and females, but there were striking differences between the two sexes. In males the enzyme activity was increased by 37% over control values and in females by 200%. The total microsomol cytochrome P-450 content was increased by 75% in males and by 82% in females. The apparent Michaelis constant (K(m)) of E/sub 2/-OH for 17..beta..-oestradiol in untreated males (9,8 ..mu..M) and females (9,2 ..mu..M) did not differ significantly. Phenobarbitone treatment, however, tended to reduce the apparent K(m) in males (8,2 ..mu..M) and to increase it in females (18,7 ..mu..M). E/sub 2/-OH activity was also detected in brain tissue of both sexes, but it was 50-200-fold lower than in the liver and was not increased by phenobarbitone.

Sex-dependent differences in phenobarbitane-induced oestradiol-2-hydroxylase activity in rat liver

International Nuclear Information System (INIS)

Theron, C.N.; Neethling, A.C.; Taljaard, J.J.F.

1981-01-01

Oestradiol-2-hydroxylase (E 2 -OH) activity was measured in liver and brain microsomes of 6-8-week-old Wistar rats. Phenobarbitone (75 mg/kg daily for 3 days) significantly increased enzyme activity in the liver of males and females, but there were striking differences between the two sexes. In males the enzyme activity was increased by 37% over control values and in females by 200%. The total microsomol cytochrome P-450 content was increased by 75% in males and by 82% in females. The apparent Michaelis constant (K(m)) of E 2 -OH for 17β-oestradiol in untreated males (9,8 μM) and females (9,2 μM) did not differ significantly. Phenobarbitone treatment, however, tended to reduce the apparent K(m) in males (8,2 μM) and to increase it in females (18,7 μM). E 2 -OH activity was also detected in brain tissue of both sexes, but it was 50-200-fold lower than in the liver and was not increased by phenobarbitone

Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in D-galactosamine-induced hepatotoxic rats.

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Pushpavalli, Ganesan; Veeramani, Chinnadurai; Pugalendi, Kodukkur Viswanathan

2008-01-01

D-galactosamine is a well-established hepatotoxicant that induces a diffuse type of liver injury closely resembling human viral hepatitis. D-galactosamine by its property of generating free radicals causes severe damage to the membrane and affects almost all organs of the human body. The leaves of Piper betle L., a commonly used masticatory in Asian countries, possess several biological properties. Our aim is to investigate the in vivo antioxidant potential of P. betle leaf-extract against oxidative stress induced by D-galactosamine intoxication in male albino Wistar rats. Toxicity was induced by an intraperitoneal injection of D-galactosamine, 400 mg/kg body weight (BW) for 21 days. Rats were treated with P. betle extract (200 mg/kg BW) via intragastric intubations. We assessed the activities of liver marker enzymes (aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase) and levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione. The extract significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, and liver marker enzymes when compared with the D-galactosamine treated group, demonstrating its hepatoprotective and antioxidant properties.

Effect of 3-keto-1,5-bisphosphonates on obese-liver's rats.

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Lahbib, Karima; Touil, Soufiane

2016-10-01

Obesity is associated with an oxidative stress status, which is defined by an excess of reactive oxygen species (ROS) vs. the antioxidant defense system. We report in this present work, the link between fat deposition and oxidative stress markers using a High Fat Diet-(HFD) induced rat obesity and liver-oxidative stress. We further determined the impact of chronic administration of 3-keto-1, 5-BPs 1 (a & b) (40μg/kg/8 weeks/i.p.) on liver's level. In fact, exposure of rats to HFD during 16 weeks induced body and liver weight gain and metabolic disruption with an increase on liver Alanine amino transférase (ALAT) and Aspartate aminotransférase (ASAT) concentration. HFD increased liver calcium level as well as free iron, whereas, it provoked a decrease on liver lipase activity. HFD also induced liver-oxidative stress status vocalized by an increase in reactive oxygen species (ROS) as superoxide radical (O 2 ), hydroxyl radical (OH) and Hydrogen peroxide (H 2 O 2 ). Consequently, different deleterious damages as an increase on Malon Dialdehyde MDA, Carbonyl protein PC levels with a decrease in non-protein sulfhydryls NPSH concentrations, have been detected. Interestingly, our results demonstrate a decrease in antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx) and peroxidases (POD). Importantly, 3-keto-1,5-bisphosphonates treatment corrected the majority of the deleterious effects caused by HFD, but it failed to correct some liver's disruptions as mineral profile, oxidative damages (PC and NPSH levels) as well as SOD and lipase activities. Our investigation point that 3-keto-1,5-bisphosphonates could be considered as safe antioxidant agents on the hepatic level that should also find other potential biological applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

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Weng-Yew Wong

2012-10-01

Full Text Available Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver

NARCIS (Netherlands)

Ballé, C.; Beuers, U.; ENGELHARDT, R.; JUNGERMANN, K.

1987-01-01

In rat liver perfused in situ stimulation of the nerve plexus around the hepatic artery and the portal vein caused an increase in glucose output and a shift from lactate uptake to output. The effects of nerve stimulation on some key enzymes, metabolites and effectors of carbohydrate metabolism were

Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats

OpenAIRE

Menon, B. Rajalakshmy; Rathi, M. A.; Thirumoorthi, L.; Gopalakrishnan, V. K.

2010-01-01

The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observ...

Prevalence of abnormal plasma liver enzymes in older people with Type 2 diabetes.

Science.gov (United States)

Morling, J R; Strachan, M W J; Hayes, P C; Butcher, I; Frier, B M; Reynolds, R M; Price, J F

2012-04-01

To determine the prevalence and distribution of abnormal plasma liver enzymes in a representative sample of older adults with Type 2 diabetes. Plasma concentrations of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were measured in a randomly selected, population-based cohort of 1066 men and women aged 60-75 years with Type 2 diabetes (the Edinburgh Type 2 Diabetes Study). Overall, 29.1% (95% CI 26.1-31.8) of patients had one or more plasma liver enzymes above the upper limit of the normal reference range. Only 10.1% of these patients had a prior history of liver disease and a further 12.4% reported alcohol intake above recommended limits. Alanine aminotransferase was the most commonly raised liver enzyme (23.1% of patients). The prevalence of abnormal liver enzymes was significantly higher in men (odds ratio 1.40, 95% CI 1.07-1.83), in the youngest 5-year age band (odds ratio 2.02, 95% CI 1.44-2.84), in patients with diabetes duration enzyme abnormality. The prevalence of elevated liver enzymes in people with Type 2 diabetes is high, with only modest variation between clinically defined patient groups. Further research is required to determine the prognostic value of raised, routinely measured liver enzymes to inform decisions on appropriate follow-up investigations. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Fibronectin binding to gangliosides and rat liver plasma membranes

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Matyas, G R; Evers, D C; Radinsky, R; Morre, D J

1986-02-01

Binding of fibronectins to gangliosides was tested directly using several different in vitro models. Using an enzyme-linked immunoabsorbent assay (ELISA), gangliosides were immobilized on polystyrene tubes and relative binding of fibronectin was estimated by alkaline phosphatase activity of conjugated second antibody. Above a critical ganglioside concentration, the gangliosides bound the fibronectin (G/sub T1b/ approx. = G/sub D1b/ approx. = G/sub D1a/ > G/sub M1/ >> G/sub M2/ approx. = G/sub D3/ approx. = G/sub M3/) in approximately the same order of efficiency as they competed for the cellular sites of fibronectin binding in cell attachment assays. Alternatively, these same gangliosides bound to immobilized fibronectin. Rat erythrocytes coated with gangliosides G/sub M1/, G/sub D1a/ or G/sub T1b/ bound more fibronectin than erythrocytes not supplemented with gangliosides. Using fibronectin in which lysine residues were radioiodinated, an apparent K/sub d/ for binding to mixed rat liver gangliosides of 7.8 x 10/sup -9/ M was determined. This value compared favorably with the apparent K/sub d/ for attachment of fibronectin to isolated plasma membranes from rat liver of 3.7 x 10/sup -9/ M for fibronectin modified on the tyrosine residue, or 6.4 x 10/sup -9/ M for fibronectin modified on lysine residues. As shown previously by Grinnell and Minter, fibronectin modified on tyrosine residues did not promote spreading and attachment of CHO cells. It did, however, bind to cells. In contrast, lysine-modified fibronectin both bound to cells and promoted cell attachment. Plasma membranes isolated from hepatic tumors in which the higher gangliosides that bind fibronectin were depleted bound 43-75% less (/sup 125/I)fibronectin than did plasma membranes from control livers. The findings were consistent with binding of fibronectins to gangliosides, including the same gangliosides depleted from cell surfaces during tumorigenesis in the rat.

Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats.

Science.gov (United States)

Nwozo, Sarah Onyenibe; Osunmadewa, Damilola Adeola; Oyinloye, Babatunji Emmanuel

2014-01-01

The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

Induction by X-irradiation of adenosine triphosphatase-deficient islands in the rat liver and their characterization

International Nuclear Information System (INIS)

Kitagawa, T.; Nomura, K.; Sasaki, S.

1985-01-01

The potential of X-rays to induce preneoplastic lesions in the rat liver was studied in order to clarify the reason why X-rays are ineffective in inducing hepatocellular carcinoma in this animal. Male newborn rats at 8 or 22 days of age received whole body X-ray irradiation of 100 to 400 rads. After weaning they were fed either basal diet or a diet containing 0.05% phenobarbital as a promoter. X-rays induced numerous adenosine triphosphatase-deficient islands appearing in the liver by wk 22 of age. However, they were generally small, gamma-glutamyl transpeptidase-negative, and did not clearly respond to the promoting stimulus of phenobarbital. No hepatic tumors were observed by 22 mo after radiation, even in phenobarbital-treated animals. Thus, the X-ray-induced enzyme-altered islands differ somewhat qualitatively from those induced by potent hepatic carcinogens and their preneoplastic potential if at all present may be very low. Similarities between these X-ray-induced lesions and some types of spontaneous enzyme-altered islands are pointed out

The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

Science.gov (United States)

Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

2016-01-01

We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the effects of hydroalcoholic extract of Berberis vulgaris root on the activity of liver enzymes in male hypercholesterolemic rats

Directory of Open Access Journals (Sweden)

Soheila Taheri

2012-06-01

Conclusion: Noticing the antioxidant properties of B. vulgaris root extract  and its effects on reducing the activity of liver enzymes, the extract of this plant can be a good choice for improving the function of liver.

Mutagenicity of comfrey (Symphytum Officinale) in rat liver

OpenAIRE

Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

2005-01-01

Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

Mutagenicity of comfrey (Symphytum Officinale) in rat liver.

Science.gov (United States)

Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

2005-03-14

Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat

DEFF Research Database (Denmark)

Breinholt, V.; Lauridsen, S. T.; Daneshvar, B.

2000-01-01

to be affected by prior. lycopene exposure. The level of PhIP-DNA adducts in the liver or colon was likewise not affected by lycopene at any dose. Overall, the present study provides evidence that lycopene administered in the diet of young female rats exerts minor modifying effects toward antioxidant and drug......-metabolizing enzymes involved in the protection against oxidative stress and cancer. The fact that these enzymatic activities are induced at all of these very low plasma levels, could be taken to suggest that modulation of antioxidant and drug-metabolizing enzymes map indeed be relevant to humans, which in general...

Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes in female rat

DEFF Research Database (Denmark)

Breinholt, V.; Lauridsen, S.T.; Dragsted, L.O.

1999-01-01

1. Gavage administration of the natural flavonoids tangeretin, chrysin, apigenin, naringenin, genistein and quercetin for 2 consecutive weeks to the female rat resulted in differential effects on selected phase 1 and 2 enzymes in liver, colon and heart as well as antioxidant enzymes in red brood......) significantly protected against, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP)-induced oxidative stress. Hepatic PhIP-DNA adduct formation was not affected by any of the administered flavonoids, whereas PhIP-DNA adduct formation in colon was slightly, but significantly, inhibited by quercetin......, genistein, tangeretin and BNF. 5. The observed effects of chrysin, quercetin and genistein on antioxidant enzymes, concurrently with a protection against oxidative stress, suggest a feedback mechanism on the antioxidant enzymes triggered by the flavonoid antioxidants. 6. Despite the use of high flavonoid...

Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease

DEFF Research Database (Denmark)

Christensen, Claus Uhrenholt; Glavind, Emilie; Thomsen, Karen Louise

2018-01-01

the last two weeks or the entire four weeks. End-points were liver/body- and spleen/body weight ratios, histopathological NASH scores, fibrosis, serum liver enzymes, cholesterol, lipoproteins, cytokines, and quantitative polymerase chain reaction derived hepatic gene expression related to cholesterol...... metabolism, inflammation, and fibrosis. RESULTS: HFHC rats developed hepatomegaly, non-fibrotic NASH histopathology, elevated liver enzymes, serum cholesterol, and pro-inflammatory cytokines. Their sterol regulatory element binding factor 2 (SREBF2) and low-density lipoprotein receptor (LDL-R) mRNAs were...... down-regulated compared with rats on standard chow. NPC2 did not improve liver weight, histopathology, levels of serum liver enzymes or pro-inflammatory tumor necrosis factor-α (TNFα), Interleukin (IL)-6, or IL-1β in HFHC rats. Two weeks of NPC2 treatment lowered hepatic TNFα and COL1A1 mRNA expression...

Daconate Herbicide Toxicity on Lipid Peroxidation And Antioxidant Enzymes in Blood of Rats

International Nuclear Information System (INIS)

Tawfik, S.M.F.

2005-01-01

The effect of daconate herbicide on lipid peroxidation and antioxidant enzyme systems was investigated in rats after one and two weeks post-treatment. Animals were treated daily with an oral dose of 18 mg/kg body weight or 90 mg/kg body weight daconate for one and two consecutive weeks. Lipid peroxide content, as thiobarbituric acid reactive substances (TBARS), was determined in blood of rats as indication for cytotoxicity. Blood glutathion (GSH), gamma glutamyl transpeptidase (γ GT) and superoxide dismutase (SOD) were estimated as indication of antioxidant status. Also, daconate effect on peroxidase action of catalase in rats was studied using 14 C -formate. The results revealed significant elevation in TBARS level and γ GT activity accompanied by reduced level of GSH content and SOD activity after treatment of rats with a daily oral dose of 90 mg/kg for one and two weeks and also in rats treated with 18 mg/kg daconate for two weeks. Rats treated with daconate at the dose level of 18 mg/kg for one week revealed non-appreciable changes in the tested parameters of blood as compared to the control ones. Radioactivities eliminated in both the expired air and in urine were reduced at the dose level of 90 mg/kg after one and two weeks, while it were reduced only after two weeks at the dose level of 18 mg/kg daconate. The data revealed that daconate had a marked effect on the activities of catalase enzyme in blood and liver of treated rats

Intralipid minimizes hepatocytes injury after anoxia-reoxygenation in an ex vivo rat liver model.

Science.gov (United States)

Stadler, Michaela; Nuyens, Vincent; Boogaerts, Jean G

2007-01-01

Ischemia-reperfusion injury is a determinant in liver injury occurring during surgical procedures, ischemic states, and multiple organ failure. The pre-existing nutritional status of the liver, i.e., fasting, might contribute to the extent of tissue injury. This study investigated whether Intralipid, a solution containing soybean oil, egg phospholipids, and glycerol, could protect ex vivo perfused livers of fasting rats from anoxia-reoxygenation injury. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Isolated livers were perfused with glucose 5.5 and 15 mM, and two different concentrations of Intralipid, i.e., 0.5:100 and 1:100 (v/v) Intralipid 10%:medium (n = 5 in each group). The experiment consisted of perfusion for 15 min, warm anoxia for 60 min, and reoxygenation during 60 min. Hepatic enzymes, potassium, glucose, lactate, bilirubin, dienes, trienes, and cytochrome-c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in biopsies. Intralipid attenuated transaminases, lactate dehydrogenase, potassium, diene, and triene release in the perfusate (dose-dependant) during the reoxygenation phase when compared with glucose-treated groups. The concentration of cytochrome-c in the medium was the highest in the 5.5-mM glucose group. The glycogen content was low in all livers at the start of the experiment. Intralipid presents, under the present experimental conditions, a better protective effect than glucose in anoxia-reoxygenation injury of the rat liver.

Black tea (camellia sinensis ) role in modulating antioxidant enzymes and biochemical changes in γ -irradiated rats

International Nuclear Information System (INIS)

Osman, N.N.; Hussien, E.M.; Farag, M.F.S.

2009-01-01

In the present work, we investigated the efficacy of camellia sinensis beverage in reducing gamma-irradiation - induced oxidative damage to the liver, lipid profile and antioxidant enzymes in adult male rats. Animals were received the black tea beverage (BTB) as a sole source of potable liquid for seven consecutive days before exposing them to single dose of 6 Gy whole-body gamma irradiation . The irradiated rats continued to receive BTB for 21 days before sacrifice. The effect of BTB was assessed by monitoring the plasma aspartate transaminase (AST), alanine transaminase (ALT), acid phosphatase (AcP), total cholesterol (TC), triglycerides (TG), high, low and very low density lipoproteins cholesterol (HDL-C,LDL-C and VLDL-C) as well as protein carbonyl content (PCC). In addition, the concentration of thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH) and catalase activity (CAT) in blood and liver of experimental rats. It was observed that tea administration lowers significantly (p< 0.05), the plasma AST, ALT, AcP activities and TC, TG, LDL-C, VLDL-C and PCC concentration as well as blood and liver TBARS. The level of GSH and activity of CAT in the blood and liver tissue were however shown to be significantly elevated (p< 0.05).The results provide useful information for future investigations and strongly implicate the beneficial application of BTB

Effect of broccoli extract enriched diet on liver cholesterol oxidation in rats subjected to exhaustive exercise.

Science.gov (United States)

Cardenia, Vladimiro; Rodriguez-Estrada, Maria Teresa; Lorenzini, Antonello; Bandini, Erika; Angeloni, Cristina; Hrelia, Silvana; Malaguti, Marco

2017-05-01

The effect of broccoli extract (BE)-enriched diet was studied in order to evaluate its ability to counteract liver cholesterol oxidation products (COPs) induced by acute strenuous exercise in rats. Thirty-two female Wistar rats were randomly divided into four groups: control diet without exercise (C), BE-enriched diet without exercise (B), control diet with acute exhaustive exercise (S) and BE-enriched diet with acute exhaustive exercise (BS). The study lasted 45days and on the last day, rats of S and BS groups were forced to run until exhaustion on a treadmill. Glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT) and cholesterol oxidation products (COPs) were determined in liver. Exhaustive exercise was clearly responsible for tissue damage, as evidenced by the increase of lactate dehydrogenase (LDH) plasma activity in the S group. Moreover, the exercise protocol reduced CAT activity in liver, while it did not affect GST, GR and GPx. BE-enriched diet raised GST, GR and CAT activities in rats of BS group. The main COPs found were 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, cholestanetriol, 24-hydroxycholesterol and 27-hydroxycholesterol. The BE-enriched diet led to reduced cholesterol oxidation following exhaustive exercise; the highest level of COPs was found in the S group, whereas the BS rats showed the lowest amount. This study indicates that the BE-enriched diet increases antioxidant enzyme activities and exerts an antioxidant effect towards cholesterol oxidation in rat liver, suggesting the use of phytochemicals in the prevention of oxidative damage and in the modulation of the redox environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of tin-protoporphyrin administration on hepatic xenobiotic metabolizing enzymes in the juvenile rat

International Nuclear Information System (INIS)

Stout, D.L.; Becker, F.F.

1988-01-01

The heme analogue tin-protoporphyrin IX (SnP) is a potent inhibitor of microsomal heme oxygenase. Administration of SnP to neonatal rats can prevent hyperbilirubinemia by blocking the postnatal increase of heme oxygenase activity. Apparently innocuous at therapeutic doses, it is of potential clinical value for chemoprevention of neonatal jaundice. We found that when 50-g male Sprague-Dawley rats were treated daily with 50 mumol of SnP/kg sc for 6 days, hepatic microsomal cytochromes b5 and P-450 were significantly diminished. Cytochrome P-450 reductase, two P-450-dependent monooxygenases, aminopyrine demethylase and benzo(a)pyrene hydroxylase, and catalase, a peroxisomal hemoprotein, were also significantly diminished. These results suggested that SnP might significantly affect the metabolism of other xenobiotics. This possibility was confirmed by the finding that hexobarbital-induced sleep lasted 4 times longer in SnP-treated rats than in controls. Inhibition of protein synthesis by SnP was ruled out as the cause of hemoprotein loss when administration of [ 3 H]leucine to SnP-treated and control rats demonstrated that proteins of the microsomal, cytosolic, and plasma membrane fractions of the livers from both groups incorporated similar levels of leucine. When 55 FeCl 3 and [2- 14 C]glycine were administered to measure heme synthesis, heme extract from the livers of SnP-treated rats contained 4 times more label from iron and glycine than did heme from control livers. Despite the apparent increased rate of heme synthesis in SnP-treated rats, each of the three cell fractions demonstrated a significant loss of heme but contained sizable amounts of SnP. These findings suggest that SnP causes a decrease of functional hemoprotein and partial loss of enzymic activity by displacing intracellular heme

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

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Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

2012-06-15

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

Sex Hormone-Related Functions in Regenerating Male Rat Liver

Science.gov (United States)

FRANCAVILLA, ANTONIO; EAGON, PATRICIA K.; DiLEO, ALFREDO; POLIMENO, LORENZO; PANELLA, CARMINE; AQUILINO, A. MARIA; INGROSSO, MARCELLO; Van THIEL, DAVID H.; STARZL, THOMAS E.

2011-01-01

Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration. PMID:3758617

In vitro metabolism of [14C]-toluene by human and rat liver microsomes and liver slices

International Nuclear Information System (INIS)

Chapman, D.E.; Moore, T.J.; Michener, S.R.; Powis, G.

1990-01-01

Toluene metabolites produced by liver microsomes from six human donors included benzylalcohol (Balc), benzaldehyde (Bald) and benzoic acid (Bacid). Microsomes from only one human donor metabolized toluene to p-cresol and o-cresol. Human liver microsomes also metabolized Balc to Bald. Balc metabolism required NADPH, was inhibited by carbon monoxide, and was decreased at a buffer pH of 10. Balc metabolism was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P450 is responsible for the in vitro metabolism of Balc by human liver microsomes. Toluene metabolites formed by human liver slices and released into the incubation media included hippuric acid, and Bacid. Cresols or cresol-conjugates were not detected in liver slice incubation media from any human donor. Toluene metabolism by human liver was compared to metabolism by comparable liver preparations from male Fischer F344 rats. Rates of toluene metabolism by human liver microsomes and liver slices were 9-fold and 1.3-fold greater than for rat liver, respectively. Covalent binding of toluene to human liver microsomes and liver slices was 21-fold and 4-fold greater than for comparable rat liver preparations. Covalent binding of toluene to human microsomes required NADPH, was significantly decreased by coincubation with 4 mM cysteine or 4 mM glutathione, and radioactivity associated with microsomes was decreased by subsequent digestion of microsomes with protease. These results suggest that toluene metabolism and covalent binding of toluene are underestimated if the male Fischer 344 rat is used as a model for human toluene metabolism

Effects of dexamethasone on liver enzymes and some serum ...

African Journals Online (AJOL)

Concomitant usage of dexamethasone and other medications may alter electrolyte metabolism and increase the formation of potentially hepatotoxic reactive metabolites which can contribute to elevated liver enzymes. The role of dexamethasone in liver functions and electrolyte metabolism during pregnancy in Yankasa ...

Hydrolysis of pyrethroids by human and rat tissues: Examination of intestinal, liver and serum carboxylesterases

International Nuclear Information System (INIS)

Crow, J. Allen; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K.

2007-01-01

Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major catabolic pathways that clear these compounds from the body. Rodent models are often used to determine the disposition and clearance rates of these esterified compounds. In this study the distribution and activities of esterases that catalyze pyrethroid metabolism have been investigated in vitro using several human and rat tissues, including small intestine, liver and serum. The major esterase in human intestine is carboxylesterase 2 (hCE2). We found that the pyrethroid trans-permethrin is effectively hydrolyzed by a sample of pooled human intestinal microsomes (5 individuals), while deltamethrin and bioresmethrin are not. This result correlates well with the substrate specificity of recombinant hCE2 enzyme. In contrast, a sample of pooled rat intestinal microsomes (5 animals) hydrolyze trans-permethrin 4.5-fold slower than the sample of human intestinal microsomes. Furthermore, it is demonstrated that pooled samples of cytosol from human or rat liver are ∼ 2-fold less hydrolytically active (normalized per mg protein) than the corresponding microsomal fraction toward pyrethroid substrates; however, the cytosolic fractions do have significant amounts (∼ 40%) of the total esteratic activity. Moreover, a 6-fold interindividual variation in carboxylesterase 1 protein expression in human hepatic cytosols was observed. Human serum was shown to lack pyrethroid hydrolytic activity, but rat serum has hydrolytic activity that is attributed to a single CE isozyme. We purified the serum CE enzyme to homogeneity to determine its contribution to pyrethroid metabolism in the rat. Both trans-permethrin and bioresmethrin were effectively cleaved by this serum CE, but deltamethrin, esfenvalerate, alpha-cypermethrin and cis-permethrin were slowly hydrolyzed. Lastly, two model lipase enzymes were examined for their ability to hydrolyze pyrethroids. However, no hydrolysis products could be detected

Follistatin allows efficient retroviral-mediated gene transfer into rat liver

International Nuclear Information System (INIS)

Borgnon, Josephine; Djamouri, Fatima; Lorand, Isabelle; Rico, Virginie Di; Loux, Nathalie; Pages, Jean-Christophe; Franco, Dominique; Capron, Frederique; Weber, Anne

2005-01-01

Retroviral vectors are widely used tools for gene therapy. However, in vivo gene transfer is only effective in dividing cells, which, in liver, requires a regenerative stimulus. Follistatin is effective in promoting liver regeneration after 90% and 70% hepatectomy in rats. We studied its efficacy on liver regeneration and retroviral-mediated gene delivery in 50% hepatectomized rats. When human recombinant follistatin was infused into the portal vein immediately after 50% hepatectomy, hepatocyte proliferation was significantly higher than in control 50% hepatectomized rats. A single injection of virus particles administered 23 h after follistatin infusion resulted in more than 20% gene transduction efficiency in hepatocytes compared to 3% in control rats. It is concluded that a single injection of follistatin induces onset of proliferation in 50% hepatectomized rats and allows efficient retroviral-mediated gene transfer to the liver

Chronic stress does not impair liver regeneration in rats

DEFF Research Database (Denmark)

Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove

2015-01-01

a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

Phospholipase activity in rat liver mitochondria studied by the use of endogenous substrates.

Science.gov (United States)

Bjornstad, P

1966-09-01

The hydrolysis of endogenous phosphatidyl ethanolamine and lecithin in rat liver mitochondria has been studied by using mitochondria from rats injected with ethanolamine-1,2-(14)C or choline-1,2-(14)C. A phospholipase A-like enzyme has been demonstrated, which catalyzes the hydrolysis of one fatty acid ester linkage in phosphatidyl ethanolamine and lecithin. Phosphatidyl ethanolamine is hydrolyzed in preference to lecithin and the main reaction products are free fatty acids and lysophosphatidyl ethanolamine. The further breakdown of lysophospholipids appears to be limited in mitochondria, which indicates that lysophospholipase activity is mainly located extramitochondrially. The enzymic system is greatly stimulated by calcium ions, and also slightly by magnesium ions, while EDTA inhibits it almost completely. These findings are discussed in relation to previous observations on the effect of calcium and of EDTA on the functions of mitochondria. The possible function of the mitochondrial phospholipase for the formation of phospholipids with special fatty acids at the alpha- and -position is discussed.

Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

Science.gov (United States)

Marcos, Ricardo; Correia-Gomes, Carla

2016-12-01

Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS.

Science.gov (United States)

Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; Khattab, Alshaimaa

2017-01-01

Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.

Efficacy of Boesenbergia rotunda Treatment against Thioacetamide-Induced Liver Cirrhosis in a Rat Model

Directory of Open Access Journals (Sweden)

Suzy M. Salama

2012-01-01

Full Text Available Background. Experimental research in hepatology has focused on developing traditional medicines into potential pharmacological solutions aimed at protecting liver from cirrhosis. Along the same line, this study investigated the effects of ethanol-based extract from a traditional medicine plant Boesenbergia rotunda (BR on liver cirrhosis. Methodology/Results. The BR extract was tested for toxicity on 3 groups of rats subjected to vehicle (10% Tween 20, 5 mL/kg and 2g/kg and 5g/kg doses of the extract, respectively. Next, experiments were conducted on a rat model of cirrhosis induced by thioacetamide injection. The rats were divided into five groups and, respectively, administered orally with 10% Tween-20 (5 mL/kg (normal control group, 10% Tween-20 (5 mL/kg (cirrhosis control group, 50 mg/kg of silymarin (reference control group, and 250 mg/kg and 500 mg/kg of BR extract (experimental groups daily for 8 weeks. The rats in normal group were intraperitoneally injected with sterile distilled water (1 mL/kg 3 times/week, and those in the remaining groups were injected intraperitoneally with thioacetamide (200 mg/kg thrice weekly. At the end of the 8 weeks, the animals were sacrificed and samples were collected for comprehensive histopathological, coagulation profile and biochemical evaluations. Also, the antioxidant activity of the BR extract was determined and compared with that of silymarin. Data from the acute toxicity tests showed that the extract was safe to use. Histological analysis of the livers of the rats in cirrhosis control group revealed uniform coarse granules on their surfaces, hepatocytic necrosis, and lymphocytes infiltration. But, the surfaces morphologically looked much smoother and the cell damage was much lesser in those livers from the normal control, silymarin and BR-treated groups. In the high-dose BR treatment group, the livers of the rats exhibited nearly normal looking lobular architecture, minimal inflammation

Changes in Liver Function Enzymes of HIV/AIDS Patients Treated ...

African Journals Online (AJOL)

user

on liver enzyme markers (Aspartate aminotransferase, Alanine aminotransferase ... the diagnosis and advanced infection of the liver cells by HIV. ... recommended guideline for the treatment of HIV ... HIV-positive patients not on treatment and.

Elevated liver enzymes in women with a family history of diabetes.

Science.gov (United States)

Inoue, Kazuo; Matsumoto, Masatoshi; Miyoshi, Yuji; Kobayashi, Yasuki

2008-03-01

Both elevated liver enzymes and a family history of diabetes mellitus (FHDM) are independent risk factors for type 2 diabetes. This study evaluates the epidemiological association between elevated liver enzymes and FHDM. Subjects included 3512 women workers without diabetes, hepatitis, a smoking habit, or a history of alcohol intake. Blood samples and personal data were collected from all subjects. Subjects with FHDM had a higher mean body mass index (BMI: 23.9kg/m(2) vs. 23.4kg/m(2); p=0.003). Laboratory testing also revealed higher mean fasting plasma glucose (FPG: 5.67mmol/L vs. 5.22mmol/L; penzymes were associated with FHDM. In particular, elevated GGT was related to FHDM, independent of the other variables. Elevated liver enzymes, probably due to fat deposition in the liver, may play a role in increasing the risk of diabetes in individuals with FHDM.

The effects of the continuous administration of N,N-dimethyl-4-phenylazoaniline (DAB) on the activities and the inducibilities of some drug-metabolizing enzymes in rat liver

DEFF Research Database (Denmark)

Autrup, Herman; Thurlow, Brenda J.; Warwick, Gerald P.

1975-01-01

of dye feeding on some of the enzyme activities in the two major liver lobes and differences were found. (3) The effect of phenobarbital (PB) pretreatment on the DAB-fed rats was studied at 4-week intervals. The activities of DAB-azoreductase and of nitroreductase increased throughout the whole period......-252-azoreductase was not induced by PB or MC, and CO did not inhibit its reduction. Its reduction depended only slightly on NADH. CO caused a greater relative decrease in the activity of DAB-azoreductase in dye-fed animals and also in animals following PB and MC pretreatment, implying a greater role of cytochrome...

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

OpenAIRE

Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

2013-01-01

This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125?mg/kg, 250?mg/kg, and 500?mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500?mg/kg body weight of free and bound polyphenols from Z. officin...

Insulin Modulates Liver Function in a Type I Diabetes Rat Model

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Eduardo L. Nolasco

2015-07-01

Full Text Available Background/Aims: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP in rats. Methods: Diabetic (alloxan, 42 mg/kg i.v., 10 days and non-diabetic (control male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a total and differential cell counts in peritoneal lavage (PeL and bronchoalveolar lavage (BAL fluids; (b quantification of tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA; (c total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d biochemical parameters (urea, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP by colorimetric analyses; and (e lung, kidney, and liver morphological analyses (hematoxylin and eosin staining. Results: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1β, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c., 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. Conclusion: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

Science.gov (United States)

Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

2017-07-01

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

Growth hormone increases and maturation decreases glutamine synthetase turnover rate in rat liver

International Nuclear Information System (INIS)

Lin, C.K.

1985-01-01

An investigation was made of the effect of hypophysectomy and growth hormone (GH) replacement regimen (1 mg/100 g twice daily for 30 days); and maturation (from 25 up to 90 days) on the liver and brain glutamine synthetase (GS) mass and turnover rates in rats. The first order decay rate of enzyme 14 C radioactivity was determined between 1 and 4 days to obtain the half-life (T/sub 1/2/) of GS. The hepatic GS mass was determined by immunoassay. GS turnover (GS/sub s/) was calculated from T/sub 1/2/ and the GS mass (i.e., K = 0.693/T/sub 1/2/; GS/sub s/ = K x GS mass). It was concluded that: (1) GS specific activity is not decreased by hypophysectomy or increased by GH. These results suggested that observed endocrine induced changes in GS are due to changes in GS mass. (2) The liver GS turnover rate is significantly reduced by hypophysectomy and increased by GH replacement. It was proposed that GH specifically enhances synthesis of GS in the liver. (3) Maturation (25, 40, 60, and 90 days) decreases GS turnover rate in both liver and brain of normal rats. This similar effect of maturation suggests that the observed age induced decline in GS turnover rate is not related to GH in all tissues

Consumption of Black Tea Infusion to Maintain the Functions of the Liver in Rats Exposed to γ-Rays

International Nuclear Information System (INIS)

Tawfik, S.S.

2015-01-01

Black tea, a phyto-compound of the fully oxidized form of Camellia sinensis has been attributed with a plethora of health-promoting actions. The role of aqueous black tea infusion (BTI) in the liver cytoprotective properties was studied using liver biochemical lesions produced by γ-rays in rat model prior oral administration of black tea infusion at 3 % (w/v) as the sole source of drinking for 10 days. Liver antioxidant properties were evaluated as, total antioxidant status (TAS), glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). In addition, Thiobarbituric reactive substances (TBARS), glutathione (GSH), triacylglycerols (TG) and total cholesterol (TC) levels were estimated. The marker enzymes of liver damage (aspartate and alanine transaminases; ALT and AST) in serum were also evaluated. Moreover, the level of plasma F2-isoprostanes (F2-IsoPs); bioactive products of lipid peroxidation was determined. Exposure of rats to γ-rays was found to cause a decrease in the liver's antioxidant abilities and provoke an increase in the level of TBARS, TG and TC. It also significantly exasperated enzymes of liver damage (ALT and AST) and the plasma F2-isoprostanes level. Supplementation of BTI prevents the changes in the liver's antioxidant abilities and in TBARS and GSH. In addition, prevents increase of oxidative stress visible as plasma F2-IsoP and decreased leak of ALT and AST into the blood. Conclusion: These results indicate that regular intake of BTI may protect γ-rays-induced oxidative damage and the consequent degenerative liver changes. The BTI consumed throughout the world is believed to be not only a popular beverage but also an anti oxidative agent available in everyday life

Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

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Adeghate, E; Hasan, M Y; Ponery, A S; Nurulain, S M; Petroianu, G A

2005-12-01

The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p catalase positive cells in the clofibrate group is higher than in the moexipril group (p inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

Effect of the aqueous extract of Psidium guajava on erythromycin-induced liver damage in rats.

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Sambo, N; Garba, S H; Timothy, H

2009-12-01

The effect of Psidium guajava extract on erythromycin-induced liver damage in albino rats was investigated using 30 normal rats grouped into six. Group I and II served as the normal and treatment controls that were administered with normal saline and 100 mg/kg body weight of erythromycin stearate daily for 14 days respectively. Rats in group III were administered 450 mg/kg body weight of Psidium guajava only for 7 days while rats in groups IV, V and VI were administered Psidium guajava extract for 7 days and 100mg/kg body weight of erythromycin for 14 days. Histopathological investigation of the liver tissues revealed striking oedema and mild periportal mononuclear cell infiltration of hepatic cords in the liver of rats administered 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract. Pretreatment with 150 mg/kg of Psidium guajava extract showed a slight degree of protection against the induced hepatic injury caused by 100 mg/kg of erythromycin stearate. Biochemical analysis of the serum obtained revealed a significant increase in serum levels of hepatic enzymes measured in the groups administered with 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract compared to the control groups and those pretreated with 150 mg/kg of Psidium guajava extract. This study has shown that the aqueous extract of psidium guajava leaf possesses hepatoprotective property at lower dose and a hepatotoxic property at higher dose but further studies with prolonged duration is recommended.

Method of preparing highly active and thermostable preparations of liver uridin-kinase usable for enzymic synthesis of radioactive nucleoside-5'-phosphates

International Nuclear Information System (INIS)

Cihak, A.; Vesely, J.

1975-01-01

A method is described of preparing a high-activity uridine kinase for the enzymic synthesis of radioactive nucleoside-5m-phosphates of the pyrimidine series. The preparation is separated from male rat liver after intraperitoneal application of 5'-azacytidine. Examples are given showing detailed procedures for the conversion of uridine and 6-azauridine to the corresponding 5'-phosphates. (L.K.)

Effects of Arctium lappa aqueous extract on lipid profile and hepatic enzyme levels of sucrose-induced metabolic syndrome in female rats

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Akram Ahangarpour

Full Text Available ABSTRACT Arctium lappa is known to have antioxidant and antidiabetic effects in traditional medicine. Objectives: The aim of this paper was to study the effects of A. lappa root extract (AE on lipid profile and hepatic enzyme levels in sucrose-induced metabolic syndrome (MS in female rats. The study used 40 adult female Wistar rats weighing 150 g-250 g randomly divided into five groups: control, metabolic syndrome (MS, metabolic syndrome+AE at 50,100, 200 mg/kg. MS was induced by administering 50% sucrose in drinking water for 6 weeks. AE was intra-peritoneally administered daily at doses of 50,100, and 200 mg/kg for two sequential weeks at the end of the fourth week in metabolic syndrome rats. Twenty-four hours after the last administration of AE, blood was collected and centrifuged, and then the serum was used for the measurement of lipid profile and hepatic enzyme. Serum glucose, insulin, fasting insulin resistance index, body weight, water intake, lipid profile, and hepatic enzymes were significantly increased although food intake was decreased in MS rats compared to the control rats. The lipids and liver enzymes were reduced by AE extracts in the MS group. This study showed that the A. lappa root aqueous extract exhibits a hypolipidemic activity of hyperlipidemic rats. This activity is practically that of a triple-impact antioxidant, hypolipidemic, and hepatoprotective.

[The effects of renin-angiotensin system blockade on the liver steatosis in rats on long-term high-fat diet].

Science.gov (United States)

Chen, Ying-Hua; Yuan, Li; Chen, Yuan-Yuan; Qi, Cui-Juan

2008-03-01

To observe the relationship between liver steatosis in rats with long-term high-caloric and high-fat diet and the expression of angiotensinogen (AGT), uncoupling protein 2 (UCP-2) and transforming growth factor beta1 (TGFbeta1). Then angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) drugs were given to investigate whether rennin-angiotensin system (RAS) blockade can mitigate the liver steatosis and to probe its mechanisms. Forty male Wistar rats were divided into normal control group (NC group, n = 10), high-calorie and high-fat fed group (HF group, n = 10), ARB treated group (AR group, n = 10) and ACEI treated group (AE group, n = 10). Rats were fed with high-calorie and high-fat diet and given RAS inhibitor drugs (valsartan 40 mg/kg to the AR group and perindopril 4 mg/kg to the AE group) for eight weeks. Serum TG, free fatty acids (FFAs) lever and the fat content in liver were then measured with biochemical tests; insulin resistance was evaluated with euglycemic hyperinsulinemia clamp technique, the expression of UCP-2 and TGFbeta1 in liver tissue were examined with immunohistochemical staining and AGT mRNA, UCP-2 mRNA and TGFbeta1 mRNA were tested with RT-PCR. With the administration of RAS inhibitor drugs, following changes were observed. The levels of TG and FFAs and the fat content in liver decreased (P liver steatosis, inflammation and fibrosis were mitigated. The levels of UCP-2 decreased by 36.5% (P liver injury of long term high-fat fed rats and have a protective effect on liver. The mechanism may be associated with the effects of improved insulin resistance, the interaction within RAS and the down-regulation of UCP-2 and TGFbeta1 in liver tissue.

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

Science.gov (United States)

Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

2015-12-01

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

EFFECT OF THIOPROPANOL ON AMINO ACID TURNOVER AND REDOX STATUS IN ALLOXAN DIABETIC RAT LIVER

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Vickram

2016-07-01

Full Text Available BACKGROUND Decreased cellular thiol levels seen in diabetes mellitus (DM may be in part attributed to increased free radical generation. The free radical mediated oxidative stress has been implicated in the pathogenesis of DM and its complications. The relative deficiency or non-availability of insulin in DM affects the metabolism of biomolecules, specifically the carbohydrate metabolism. The insulin-mimicking actions of various thiols have been studied. In our previous study, we have documented that 3-mercapto- 1-propanol (Thiopropanol, a low molecular weight thiol, at the dosage employed has increased glucose utilisation in alloxandiabetic rat liver tissue probably by favouring utilisation of glucose through glycolysis and HMP pathway. It is known that insulin inhibits gluconeogenesis by inhibiting the key enzymes of the same and by controlling the channelling of amino acids for the glucose biosynthesis through gluconeogenic pathway. A study was undertaken to assess the effects of thiopropanol (TP on amino acid turnover and the redox status in alloxan diabetic rat liver. METHODS Male albino rats weighing 150-250 g were used. Diabetes was induced using alloxan monohydrate. Rats were divided into normal and diabetic groups. Levels of amino acid nitrogen (AAN, alanine, total thiol (-SH groups, TBARS (Thiobarbituric acid reactive substances, and activities of alanine transaminase (ALT and aspartate transaminase (AST were estimated in liver specimens of normal, control-alloxan diabetic and TP-exposed-alloxan-diabetic rats. RESULTS The results showed a significant increase (p<0.001 in AAN levels, alanine levels, and total -SH groups concentration; and a significant decrease (p<0.001 in TBARS levels, ALT and AST activities in TP-exposed-alloxan diabetic liver slices as compared to control-alloxan diabetic liver slices. CONCLUSIONS Hence, it may be concluded that TP, at the concentration employed, inhibits gluconeogenesis from amino acids probably by

Biochemical assessement of liver enzymes in immunocompromised ...

African Journals Online (AJOL)

Aim: This study aims at the estimation of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and glutmyltransferase GGT (Liver enzymes) in Human immunodeficiency virus(HIV) and/or Acquired immune deficiency syndrome(AIDS) patients in parts of Edo State, Nigeria.

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

Science.gov (United States)

Alkafafy, Mohamed El-Sayed; Ibrahim, Zein Shaban; Ahmed, Mohamed Mohamed; El-Shazly, Samir Ahmed

2015-06-01

The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure. © The Author(s) 2015.

Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

International Nuclear Information System (INIS)

Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-Mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

2011-01-01

β-Naphthoflavone (BNF) is a strong inducer of cytochrome P450 1A enzymes, and exerts liver tumor-promoting activity through enhancement of oxidative stress responses in rats. This study investigated the role of the tissue environment surrounding hepatocellular preneoplastic lesions in the early tumor-promotion stage by BNF, using enzymatically modified isoquercitrin (EMIQ) as an anti-oxidative chemopreventive agent. Male F344 rats were fed a diet containing BNF (0.5%) for 6 weeks, with or without EMIQ (0.2%) in the drinking water, 2 weeks after initiation with N-diethylnitrosamine, and were subjected to two-thirds partial hepatectomy 1 week after starting BNF-promotion. BNF-treatment increased concentrations of liver thiobarbituric acid-reactive substances, single liver cells expressing glutathione S-transferase placental form or heme oxygenase (HO)-1, and concomitant apoptosis and proliferation of liver cells. Transcript upregulation of anti-oxidative enzymes (Aldh1a1 and Nqo1), cell cycle-related molecules (Cdc20 and Cdkn2b) and inflammation-related molecules including proinflammatory cytokines (Ccl2, Col1a1, Il6, Nos2 and Serpine1) was also evident. Furthermore, BNF increased HO-1-expressing Kupffer cells and liver cells expressing tumor necrosis factor receptor 1 (TNFR1) and the TNFR1-associated death domain. Most of these BNF-induced fluctuations disappeared or were suppressed by EMIQ in conjunction with suppression of tumor-promotion. Tnf transcript levels with BNF were also suppressed by EMIQ. These results suggest that BNF-induced oxidative stress causes single liver cell toxicity, allowing subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFα-signaling, contributing to tumor promotion. Kupffer cells may act to protect against inflammatory stimuli induced as a result of oxidative cellular stress by BNF, causing proinflammatory cytokine level fluctuations.

Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

International Nuclear Information System (INIS)

Lanza-Jacoby, S.; Tabares, A.

1990-01-01

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats

Changing Interdigestive Migrating Motor Complex in Rats under Acute Liver Injury

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Mei Liu

2014-01-01

Full Text Available Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by D-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

Chronotherapeutic effect of fisetin on expression of urea cycle enzymes and inflammatory markers in hyperammonaemic rats.

Science.gov (United States)

Subramanian, Perumal; Jayakumar, Murugesan; Jayapalan, Jaime Jacqueline; Hashim, Onn Haji

2014-12-01

Elevated blood ammonia leads to hyperammonaemia that affects vital central nervous system (CNS) functions. Fisetin, a naturally occurring flavonoid, exhibits therapeutic benefits, such as anti-cancer, anti-diabetic, anti-oxidant, anti-angiogenic, neuroprotective and neurotrophic effects. In this study, the chronotherapeutic effect of fisetin on ammonium chloride (AC)-induced hyperammonaemic rats was investigated, to ascertain the time point at which the maximum drug effect is achieved. The anti-hyperammonaemic potential of fisetin (50mg/kg b.w. oral) was analysed when administered to AC treated (100mg/kg b.w. i.p.) rats at 06:00, 12:00, 18:00 and 00:00h. Amelioration of pathophysiological conditions by fisetin at different time points was measured by analysing the levels of expression of liver urea cycle enzymes (carbamoyl phosphate synthetase-I (CPS-I), ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS)), nuclear transcription factor kappaB (NF-κB p65), brain glutamine synthetase (GS) and inducible nitric oxide synthase (iNOS) by Western blot analysis. Fisetin increased the expression of CPS-I, OTC, ASS and GS and decreased iNOS and NF-κB p65 in hyperammonaemic rats. Fisetin administration at 00:00h showed more significant effects on the expression of liver and brain markers, compared with other time points. Fisetin could exhibit anti-hyperammonaemic effect owing to its anti-oxidant and cytoprotective influences. The temporal variation in the effect of fisetin could be due to the (i) chronopharmacological, chronopharmacokinetic properties of fisetin and (ii) modulations in the endogenous circadian rhythms of urea cycle enzymes, brain markers, redox enzymes and renal clearance during hyperammonaemia by fisetin. However, future studies in these lines are necessitated. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. Pt. 2

International Nuclear Information System (INIS)

Kido, Hiroshi; Higashi, Takao; Katanuma, Nobuhiko

1977-01-01

1) An amplifier of the action of glucocorticoid was purified from Proteus mirabilis as described previously. It was found that it amplified the induction of liver tyrosine aminotransferase by dexamethasone markedly with doses of dexamethasone that caused minimal enzyme induction, but had little effect with doses that caused maximal induction. Thus the amplification may represent a saving of glucocorticoid. The amplification of enzyme activity was brought about by increase in amount of enzyme. 2) The amplification was observed when the amplifier was administered before or with dexamethasone, but not when it was given 2 h after dexamethasone. These results and the finding that actinomycin D inhibited the amplification indicate that the amplifier does not act on the translational level of enzyme induction. 3) It was found that the amplifier increased both incorporation of [ 3 H]dexamethasone into the cytosol and binding of [ 3 H]dexamethasone to cytosol protein and that it decreased decay of the [ 3 H]dexamethasone protein complex. (orig.) [de

Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats.

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Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Rosângela Fernandes; Cecchini, Alessandra Lourenço; Natali, Maria Raquel Marçal; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2015-01-01

Vitex agnus-castus (VAC) is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD), frequently associated with menopause. Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period.

Vitex agnus-castus L. (Verbenaceae Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

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Franciele Neves Moreno

2015-01-01

Full Text Available Vitex agnus-castus (VAC is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD, frequently associated with menopause. Ovariectomized (OVX rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE and a butanolic fraction of VAC (ButF and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period.

Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

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Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Rosângela Fernandes; Cecchini, Alessandra Lourenço; Natali, Maria Raquel Marçal; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2015-01-01

Vitex agnus-castus (VAC) is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD), frequently associated with menopause. Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period. PMID:25954315

Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes.

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Latha, M; Pari, L

2004-04-01

The effects of an aqueous extract of the plant Scoparia dulcis (200 mg/kg) on the polyol pathway and lipid peroxidation were examined in the liver of streptozotocin adult diabetic male albino Wistar rats. The diabetic control rats (N = 6) presented a significant increase in blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides, and a significant decrease in plasma insulin and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) compared to normal rats (N = 6). Scoparia dulcis plant extract (SPEt, 200 mg kg-1 day-1) and glibenclamide (600 microg kg-1 day-1), a reference drug, were administered by gavage for 6 weeks to diabetic rats (N = 6 for each group) and significantly reduced blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin, TBARS, and hydroperoxides, and significantly increased plasma insulin, GPx, GST and GSH activities in liver. The effect of the SPEt was compared with that of glibenclamide. The effect of the extract may have been due to the decreased influx of glucose into the polyol pathway leading to increased activities of antioxidant enzymes and plasma insulin and decreased activity of sorbitol dehydrogenase. These results indicate that the SPEt was effective in attenuating hyperglycemia in rats and their susceptibility to oxygen free radicals.

Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes

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M. Latha

2004-04-01

Full Text Available The effects of an aqueous extract of the plant Scoparia dulcis (200 mg/kg on the polyol pathway and lipid peroxidation were examined in the liver of streptozotocin adult diabetic male albino Wistar rats. The diabetic control rats (N = 6 presented a significant increase in blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS and hydroperoxides, and a significant decrease in plasma insulin and antioxidant enzymes such as glutathione peroxidase (GPx, glutathione-S-transferase (GST and reduced glutathione (GSH compared to normal rats (N = 6. Scoparia dulcis plant extract (SPEt, 200 mg kg-1 day-1 and glibenclamide (600 µg kg-1 day-1, a reference drug, were administered by gavage for 6 weeks to diabetic rats (N = 6 for each group and significantly reduced blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin, TBARS, and hydroperoxides, and significantly increased plasma insulin, GPx, GST and GSH activities in liver. The effect of the SPEt was compared with that of glibenclamide. The effect of the extract may have been due to the decreased influx of glucose into the polyol pathway leading to increased activities of antioxidant enzymes and plasma insulin and decreased activity of sorbitol dehydrogenase. These results indicate that the SPEt was effective in attenuating hyperglycemia in rats and their susceptibility to oxygen free radicals.

Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats.

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Asgharzadeh, Fereshteh; Bargi, Rahimeh; Beheshti, Farimah; Hosseini, Mahmoud; Farzadnia, Mehdi; Khazaei, Majid

2017-01-01

Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. LPS group showed higher levels of fibrosis and collagen content stained by Masson's trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (pliver fibrosis, improved liver function tests and increased the levels of anti-oxidative enzymes (SOD and catalase), while reduced MDA concentration (pliver fibrosis possibly through affecting oxidative stress status. It seems that administration of TQ can be considered as a part of liver fibrosis management.

EFFECTS OF PARTIAL HEPATECTOMY, PHENOBARBITAL AND 3-METHYLCHOLANTHRENE ON KINETIC-PARAMETERS OF GLUCOSE-6-PHOSPHATE AND PHOSPHOGLUCONATE DEHYDROGENASE IN-SITU IN PERIPORTAL, INTERMEDIATE AND PERICENTRAL ZONES OF RAT-LIVER LOBULES

NARCIS (Netherlands)

Jonges, G. N.; Vogels, I. M. C.; van Noorden, C. J. F.

1995-01-01

Glucose-6-phosphate dehydrogenase (G6PDH) and phosphogluconate dehydrogenase (PGDH) are heterogeneously distributed in liver lobules of female rats. The maximum activity of both enzymes is approximately twice higher in intermediate and pericentral zones than in periportal zones. Enzyme activities

Effects of 1 alpha,25-Dihydroxyvitamin D-3 on Transporters and Enzymes of the Rat Intestine and Kidney In Vivo

NARCIS (Netherlands)

Chow, Edwin C. Y.; Sun, Huadong; Khan, Ansar A.; Groothuis, Geny M. M.; Pang, K. Sandy

1 alpha,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3), the natural ligand of the vitamin D receptor (VDR), was found to regulate bile acid related transporters and enzymes directly and indirectly in the rat intestine and liver in vivo. The kidney is another VDR-rich target organ in which VDR regulation

Properties of the ATPase activity associated with peroxisome-enriched fractions from rat liver: comparison with mitochondrial F1F0-ATPase

NARCIS (Netherlands)

Wolvetang, E. J.; Wanders, R. J.; Schutgens, R. B.; Berden, J. A.; Tager, J. M.

1990-01-01

Highly purified peroxisomal fractions from rat liver contain ATPase activity (18.8 +/- 0.1 nmol/min per mg, n = 6). This activity is about 2% of that found in purified mitochondrial fractions. Measurement of marker enzyme activities and immunoblotting of the peroxisomal fraction with an antiserum

Effect of the Combination of Ezetimibe and Simvastatin on Gluconeogenesis and Oxygen Consumption in the Rat Liver.

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Bracht, Lívia; Caparroz-Assef, Silvana Martins; Bracht, Adelar; Bersani-Amado, Ciomar Aparecida

2016-06-01

The aim of this work was to investigate the effects of chronic treatment with the combination of ezetimibe and simvastatin on gluconeogenesis in rat liver. Rats were treated daily for 28 days with the combination of ezetimibe and simvastatin (10/40 mg/kg) by oral gavage. To measure gluconeogenesis and the associated pathways, isolated perfused rat liver was used. In addition, subcellular fractions, such as microsomes and mitochondria, were used for complementary measures of enzymatic activities. Treatment with the combination of simvastatin and ezetimibe resulted in a decrease in gluconeogenesis from pyruvate (-62%). Basal oxygen consumption of the treated animals was higher (+22%) than that of the control rats, but the resulting oxygen consumption that occurred after pyruvate infusion was 43% lower in animals treated with the combination of simvastatin and ezetimibe. Oxygen consumption in the livers from treated animals was completely inhibited by cyanide (electron transport chain inhibitor), but not by proadifen (cytochrome P450 inhibitor). Chronic treatment with ezetimibe/simvastatin decreased the activity of the key enzymes glucose-6-phosphatase and fructose-1,6-bisphosphatase by 59% and 45%, respectively, which is probably the major reason for the decreased gluconeogenesis seen in ezetimibe-/simvastatin-treated rats. It is also possible that part of the effect of this combination on gluconeogenesis and on the oxygen consumption is related to the impairment of mitochondrial energy transduction. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Possible role of Arthrospira platensis in reversing oxidative stress-mediated liver damage in rats exposed to lead.

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Khalil, Samah R; Elhady, Walaa M; Elewa, Yaser H A; Abd El-Hameed, Noura E; Ali, Sozan A

2018-01-01

Environmental pollutants, particularly metallic elements, mobilized and released into the environment, eventually accumulate in the food chain and thus pose a serious threat to human and animal health. In the present study, the role of Arthrospira (Spirulina platensis; SP) as a protector against oxidative stress-mediated liver damage induced by an exposure to lead acetate (LA; as a metallic pollutant) was assessed. To achieve this aim, rats were orally administered with 300 mg/kg bw SP for 15 days, before and concurrently with an intraperitoneal injection of 50 mg/kg bw LA (6 injections throughout 15 days). As a result, co-administration of SP with LA reduced the amount of lead that accumulated in both blood and liver tissue of the exposed rats and minimized the increased levels of lipid peroxidation, protein oxidation, DNA oxidative damage, and liver enzyme endpoints. In addition, because of SP administration, the levels of depleted biomarkers of antioxidant status and total antioxidant capacity in LA-exposed rats improved. Moreover, SP protected the liver tissue against the changes caused by LA exposure and also decreased the reactivity of HSP70 in the cytoplasm of hepatocytes. Collectively, our data suggest that SP has a potential use as a food supplement in the regions highly polluted with heavy metals such as lead. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Virtual determination of liver and muscle glycogen obtained from fed rats and from 24-hour fasted rats

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V.M.T.T. Trindidade et al

2014-08-01

Full Text Available Introduction: Glycogen is the storage polysaccharide of animals, composed by glucoseresidues forming a branched polymer. The liver glycogen metabolism and hepaticgluconeogenesis are important buffer systems of blood glucose in different physiological orpathological situations, such as, during a fast period. Fasting muscle glycogenolysis alsooccurs, however, the release of glucose into the bloodstream is negligible because themuscle doesn’t have the enzyme glucose-6-P phosphatase, which is present in the liver.Objectives: This panel presents a learning object, mediated by computer, which simulatesthe determination of liver and muscle glycogen obtained from fed rats and from 24-hourfasted rats Materials and Methods: At first, cartoons were planned in order to show themethodology procedures and biochemical fundamentals. The most representative imageswere selected, edited, organized in a scene menu and inserted into an animationdeveloped with the aid of the Adobe ® Flash 8 software. The validation of this object wasperformed by the students of Biochemistry I (Pharmacy-UFRGS from the secondsemester of 2009 until the second semester of 2013. Results and Discussion: Theanalysis of students' answers revealed that 83% of them attributed the excellence rate tothe navigation program, to the display format and to the learning help. Conclusion:Therefore, this learning object can be considered an adequate teaching resource as wellas an innovative support in the construction of theoretical and practical knowledge ofBiochemistry. Support: SEAD-UFRGSAvailable at: http://www.ufrgs.br/gcoeb/obtencaodosagemglicogenio/

A case of moderate liver enzyme elevation after acute acetaminophen overdose despite undetectable acetaminophen level and normal initial liver enzymes.

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Bebarta, Vikhyat S; Shiner, Drew C; Varney, Shawn M

2014-01-01

Liver function test (LFT) increase is an early sign of acetaminophen (APAP) toxicity. Typically, when an acute overdose patient is evaluated and has an initial undetectable APAP level and normal liver enzymes, the patient is not treated with N-acetylcysteine, and liver enzymes are not expected to increase later. We report a case of moderate LFT increase despite normal LFTs and an undetectable APAP level after delayed presentation of an APAP ingestion. A 22-year-old male with no medical history ingested 15-25 hydrocodone/APAP tablets (5 mg/500 mg). His suicide note and his bunkmate corroborated the overdose time. He arrived at the emergency department 16 hours after ingestion. At that time, his APAP level was enzymes were normal [aspartate transaminase (AST) 31 U/L and alanine transaminase (ALT) 34 U/L]. Twenty-nine hours after ingestion, the psychiatry team obtained LFTs (AST 45, ALT 61). He had persistent nausea and diffuse abdominal pain. On repeat analysis, the APAP level at 36 hours was found to be <10 μg/mL, AST 150, and ALT 204. After 2 more days of increasing LFTs and persistent abdominal pain and nausea, the toxicology department was consulted, the patient was transferred to the medicine department, and intravenous N-acetylcysteine was started 66 hours after ingestion. He was treated for 16 hours and had a significant decline in LFTs and symptom resolution. His prothrombin time, bilirubin, lactate, creatinine, and mental status were normal throughout the admission. Other cases of LFT increase were excluded. Our case report illustrates that a moderate increase in liver transaminase may occur despite an initial undetectable APAP level and normal transaminases after a delayed presentation. In our case, no serious clinical effects were reported.

Molecular cloning and nucleotide sequence of cDNA for human liver arginase

International Nuclear Information System (INIS)

Haraguchi, Y.; Takiguchi, M.; Amaya, Y.; Kawamoto, S.; Matsuda, I.; Mori, M.

1987-01-01

Arginase (EC3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, the authors isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in λ gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated λ hARG6 and λ hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted M/sub r/, 34,732), a 5'-untranslated sequence of 56 base pairs, a 3'-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying λ hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat, and yeast enzymes

Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver

International Nuclear Information System (INIS)

Katz, M.S.; Boland, S.R.; Schmidt, S.J.

1985-01-01

beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[ 125 I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase

Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats.

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Aktas, Cevat; Kanter, Mehmet; Erboga, Mustafa; Mete, Rafet; Oran, Mustafa

2014-10-01

The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress. © The Author(s) 2012.

Borax counteracts genotoxicity of aluminum in rat liver.

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Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

2013-10-01

This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.

Alloxan-Induced Diabetes Causes Morphological and Ultrastructural Changes in Rat Liver that Resemble the Natural History of Chronic Fatty Liver Disease in Humans

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Amanda Natália Lucchesi

2015-01-01

Full Text Available Purpose. This study evaluated the long-term effects of alloxan-induced diabetes in rat liver. Methods. Thirty nondiabetic control rats (NC and 30 untreated diabetic (UD rats were divided into three subgroups sacrificed after 6, 14, or 26 weeks. Clinical and laboratory parameters were assessed. Fresh liver weight and its relationship with body weight were obtained, and liver tissue was analyzed. Results. UD rats showed sustained hyperglycemia, high glycosylated hemoglobin, and low plasma insulin. High serum levels of AST and ALT were observed in UD rats after 2 weeks, but only ALT remained elevated throughout the experiment. Fresh liver weight was equal between NC and UD rats, but the fresh liver weight/body weight ratio was significantly higher in UD rats after 14 and 26 weeks. UD rats showed liver morphological changes characterized by hepatic sinusoidal enlargement and micro- and macrovesicular hepatocyte fatty degeneration with progressive liver structure loss, steatohepatitis, and periportal fibrosis. Ultrastructural changes of hepatocytes, such as a decrease in the number of intracytoplasmic organelles and degeneration of mitochondria, rough endoplasmic reticulum, and nuclei, were also observed. Conclusion. Alloxan-induced diabetes triggered liver morphological and ultrastructural changes that closely resembled human disease, ranging from steatosis to steatohepatitis and liver fibrosis.

Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

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Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

2009-07-01

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

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Qin, Lu-shan; Zhao, Hai-ping; Zhao, Yan-ling; Ma, Zhi-jiel; Zeng, Ling-na; Zhang, Ya-ming; Zhang, Ping; Yan, Dan; Bai, Zhao-fang; Li, Yue; Hao, Qing-xiu; Zhao, Kui-jun; Wang, Jia-bo; Xiao, Xiao-he

2014-06-01

To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. Compared with the blank control group, all biochemical indices increased in the blank group (P analysis. TA showed stronger improvement of the two common factors than TT. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

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Fatemeh Sarhadi Kholari

2016-11-01

Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

High affinity binding of [3H]cocaine to rat liver microsomes

International Nuclear Information System (INIS)

El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

1988-01-01

] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

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Michiel Sala

Full Text Available OBJECTIVE: Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT. RESEARCH DESIGN AND METHODS: We measured nonfasting alanine transaminase (ALT, aspartate aminotransferase (AST, and Υ-glutamyl transferase (GGT in 1625 subjects (736 men, mean age 59.1 years from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230 were evaluated and CT was performed (n = 268 for assessment of liver-spleen (L/S ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD. Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. RESULTS: Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03, while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively. CONCLUSIONS: Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver

Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

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Sala, Michiel; Kroft, Lucia J M; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P Eline; Mooijaart, Simon P; de Roos, Albert; van Heemst, Diana

2014-01-01

Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and

Metabolism of 1-[14C]nitropyrene in isolated perfused rat livers

International Nuclear Information System (INIS)

Bond, J.A.; Medinsky, M.A.; Dutcher, J.S.

1984-01-01

1-Nitropyrene (1-NP), a constituent of diesel exhaust, is carcinogenic to rats and is a bacterial and mammalian mutagen. Biliary and fecal excretion of 1-NP metabolites are the major routes of excretion in rats, suggesting that hepatic metabolism plays a dominant role in determining the biological fate of 1-NP. The purpose of this investigation was to quantitate 1-[14C]NP metabolites formed in isolated perfused rat livers and excreted in bile from rats. Perfused rat livers displayed a capacity for oxidation, reduction, acetylation, and conjugation of 1-NP (or its metabolites). Reduction of 1-NP followed by N-acetylation was the major metabolic pathway observed in the perfused livers. Acetylaminopyrene (AAP) was the major metabolite detected, with total quantities (150 nmol) accounting for about 60% of the total 1-[14C]NP dose (258 nmol) added to the perfusate. Considerably smaller quantities of aminopyrene and hydroxynitropyrenes were also detected. Livers perfused with 1-[14C]NP excreted about 36 nmol equivalents of 1-[14C]NP (12% of the total 1-NP dose) in bile after 60 min. Some of the biliary metabolites were tentatively identified as metabolites of the mercapturic acid pathway. The spectrum of biliary metabolites was qualitatively identical to that seen in bile from intact rats. Quantities of 14C covalently bound to hepatic macromolecules from perfused livers were 0.4 nmol 1-NP eq/g liver. The data from this study indicate that the liver may be an important site for metabolism of 1-NP

Effect of aqueous extract of Capparis spinosa on biochemical and histological changes in paracetamol–induced liver damage in rats

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R. J. M. Alnuaimy

2012-01-01

Full Text Available This study showed that paracetamol administration to male rats at 1 g /kg of body weight for 21 days resulted in significant increase in activities of serum alanine amino transferase and aspartate amino transferase. There was an increase in the total bilirubin and creatinine levels. Paracetamol caused hepatic damage in appearance characterized with degeneration, necrosis and fatty changes in liver, as well as central vein congestion. Treatment of the damaged liver rats with 25, 50, 100, 200 mg/kg of body weight with aqueous extract of Capparis spinosa for 7, 14, 21 days led to a decrease in alanine amino transferase, aspartate amino transferase activity, total bilirubin and creatinine levels, as well as an improve in the damaged liver tissues with increasing extract concentration. The results showed that treatment of the damaged liver rats with 100, 200 mg/kg of body weight of aqueous extract of Capparis spinosa for 14, 21 days gave protection against harmful effects of paracetamol.The protective effects of this extract determined by the rebound of the enzymes and biochemical variable levels to the pretreatment levels. High doses of this extract gave a decrease in harmful effects which resulted from the paracetamol in hepatic tissues.

Vitamin K1 attenuates bile duct ligation-induced liver fibrosis in rats.

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Jiao, Kun; Sun, Quan; Chen, Baian; Li, Shengli; Lu, Jing

2014-06-01

Vitamin K1 is used as a liver protection drug for cholestasis-induced liver fibrosis in China, but the mechanism of vitamin K1's action in liver fibrosis is unclear. In this study, a model of liver fibrosis was achieved via bile duct ligation in rats. The rats were then injected with vitamin K1, and the levels of serum aspartate aminotransferase, alanine transaminase, total bilirubin and the fibrotic grade score, collagen content, the expressions of α-smooth muscle actin (SMA) and cytokeratin 19 (CK19) were measured on day 28 after ligation. The levels of the biochemical parameters, fibrotic score and collagen content were significantly reduced by treatment with vitamin K1 in bile duct-ligated rats. In addition, α-SMA and CK19 expression was significantly reduced by vitamin K1 treatment in bile duct-ligated rats. These results suggested that vitamin K1 may attenuate liver fibrosis by inhibiting hepatic stellate cell activation in bile duct-ligated rats.

Hepatoprotective activity of Rhus oxyacantha root cortex extract against DDT-induced liver injury in rats.

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Ben Miled, Hanène; Barka, Zaineb Ben; Hallègue, Dorsaf; Lahbib, Karima; Ladjimi, Mohamed; Tlili, Mounira; Sakly, Mohsen; Rhouma, Khémais Ben; Ksouri, Riadh; Tebourbi, Olfa

2017-06-01

The present investigation aimed to study the antioxidant activity and hepatoprotective effects of ethyl acetate extract of R. oxyacantha root cortex (RE) against DDT-induced liver injury in male rats. The RE exhibited high total phenolic, flavonoid and condensed tannins contents. The antioxidant activity in vitro systems showed a significant potent free radical scavenging activity of the extract. The HPLC finger print of R. oxyacantha active extract showed the presence of five phenolic compounds with higher amounts of catechol and gallic acid. The in vivo results showed that a single intraperitoneal administration of DDT enhanced levels of hepatic markers (ALT, AST and LDH) in serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a significant induction of SOD and GPx, metallothioneins (MTs) and a concomitant decrease of non protein thiols (NPSH) in liver. However, pretreatment of rats with RE at a dose of 150 and 300mg/kg body weight significantly lowered serum transaminases and LDH in treated rats. A significant reduction in hepatic thiobarbituric reactive substances and a decrease in antioxidant enzymes activities and hepatic MTs levels by treatment with plant extract against DDT, were observed. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of RE with the two doses used. These results strongly suggest that treatment with ethyl acetate extract normalizes various biochemical parameters and protects the liver against DDT-induced oxidative damage in rats and thus help in evaluation of traditional claim on this plant. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mitochondria As the Target for the Modulatory Effect of Curcumin in Oxaliplatin-induced Toxicity in Isolated Rat Liver Mitochondria.

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Waseem, Mohammad; Parvez, Suhel; Tabassum, Heena

2017-01-01

To explore hepatoprotective action of curcumin (CMN, a bioflavonoid) on oxaliplatin (Oxa)-triggered mitochondrial oxidative stress and respiratory chain complexes in liver of rats. Oxa is a ubiquitously utilized platinum-based chemotherapeutic agent commonly used for the treatment of colorectal cancer. Mitochondria have recently emerged as targets for anticancer drugs in several kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. There is a dearth of evidence involving the role of mitochondria in mediating Oxa-evoked hepatotoxicity and its underlying mechanism is still debatable. The study was performed in mitochondria isolated from liver of Wistar rats. Oxa (200 μg/mL) and CMN (5 μmol) were incubated under in vitro conditions. Oxa evoked a significant increase in the membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, decrease in reduced glutathione (GSH) and nonprotein thiol (NP-SH) levels. Oxa also caused a marked decline in the activities of enzymatic antioxidants and respiratory chain enzymes (I, II, III and V) in liver mitochondria. CMN pre-treatment significantly prevented the activities of enzymatic antioxidants and mitochondrial respiratory chain enzymes. CMN also restored the LPO and PC contents, GSH and NP-SH levels in liver mitochondria. CMN intake might be effective in regulation of Oxa-evoked mitotoxicity during chemotherapy. Moreover, it is included in the armamentarium for anticancer agent-induced oxidative stress. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Immunohistochemical Analysis of Platelet Extract Effects on Liver Injury Induced by CCl4 in Male Rats

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Zahra Hesami

2016-01-01

Full Text Available Backgrounds & objectives: Liver damage results in a large accumulation of external cellular matrix that affects the function of this important body organ in a long term and finally stops its function completely. The growth factors existing in platelet extract are more cost-effective, available, and stable than recombinant ones. To determine whether the platelet extract effects on histological changes in liver injury induced by carbon tetrachloride (CCl4, we used immunohistochemical analysis in male rats. Methods: In this project the 28 male Wistar rats (250-300 g were randomly divided into 4 groups, each consisting of 7 animals. The rats were divided into four experimental groups as follows: the first group (sham intraperitoneally received only olive oil as the solvent of carbon tetrachloride; second group (CCl4 intraperitoneally received carbon tetrachloride dissolved in olive oil (ratio of about 1: 1 at a concentration of 1 ml/kg and a twice a week for eight weeks; third group subcutaneously received only platelet extract at a concentration of 0.5 ml/kg twice a week for three weeks; and fourth group received both CCl4 intraperitoneally for eight weeks and platelet extract subcutaneously for last three weeks. After 8 weeks of trial blood and liver sampling were done. Blood samples sent for enzymatic (AST, ALT tests and liver samples tested for histological and immunohistochemical studies. The data were analyzed using  one-way ANOVA followed by Tukey test by Graph pad Prism 5 software and data were considered significant at p≤ 0.05. Results: The results show that platelet extract causes a significant (p≤ 0.001 decrease in liver enzymes and albumin improves the function of liver. The level of alfa smooth muscle actin (α-SMA as an index of hepatic stellate cell activation was decreased by platelet extract administration which eventually reduced the necrosis and fibrosis induced by carbon tetrachloride in studied rats

A Novel Wistar Rat Model of Obesity-Related Nonalcoholic Fatty Liver Disease Induced by Sucrose-Rich Diet

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Maria Luíza R. P. Lima

2016-01-01

Full Text Available The pathogenesis of nonalcoholic fatty liver disease (NAFLD is not fully understood, and experimental models are an alternative to study this issue. We investigated the effects of a simple carbohydrate-rich diet on the development of obesity-related NAFLD and the impact of physical training on the metabolic abnormalities associated with this disorder. Sixty Wistar rats were randomly separated into experimental and control groups, which were fed with sucrose-enriched (18% simple carbohydrates and standard diet, respectively. At the end of each experimental period (5, 10, 20, and 30 weeks, 6 animals from each group were sacrificed for blood tests and liver histology and immunohistochemistry. From weeks 25 to 30, 6 animals from each group underwent physical training. The experimental group animals developed obesity and NAFLD, characterized histopathologically by steatosis and hepatocellular ballooning, clinically by increased thoracic circumference and body mass index associated with hyperleptinemia, and metabolically by hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased levels of very low-density lipoprotein- (VLDL- cholesterol, depletion of the antioxidants liver enzymes superoxide dismutase and catalase, and increased hepatic levels of malondialdehyde, an oxidative stress marker. Rats that underwent physical training showed increased high-density lipoprotein- (HDL- cholesterol levels. In conclusion, a sucrose-rich diet induced obesity, insulin resistance, oxidative stress, and NAFLD in rats.

Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

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Ellouz Meriem

2010-10-01

Full Text Available Abstract Background Olive oil's beneficial effects are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. In this study, we assess the effects of virgin olive oil and its fractions on 2,4-D- induced oxidative damage in the liver of rats. Methods Male Wistar rats were randomly divided into eight groups of ten each: (C a control group, (D group that received 2,4-D (5 mg/kg b.w., (D/EVOO group treated with 2,4-D plus extra virgin olive oil, (D/OOHF group that received 2,4-D plus hydrophilic fraction, (D/OOLF group treated with 2,4-D plus lipophilic fraction, (EVOO group that received only extra virgin olive oil, (OOHF group given hydrophilic fraction and (OOLF group treated with lipophilic fraction. These components were daily administered by gavage for 4 weeks. Results A significant liver damage was observed in rats treated with 2,4-D via increased serum levels of transaminases and alkaline phosphatase, hepatic lipid peroxidation and decreased hepatic antioxidant enzyme activities, namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The liver's fatty acid composition was also significantly modified with 2,4-D exposure. However, extra virgin olive oil and hydrophilic fraction intake during 2,4-D treatment induced a significant increase in the antioxidant enzyme activities and a decrease in the conjugated dienes (CD and thiobarbituric acid-reactive substances (TBARs levels in the liver. The lipophilic fraction supplemented to 2,4-D- treated rats did not show any improvement in the liver oxidative status while a marked improvement was detected in the hepatic fatty acid composition of rats supplemented with olive oil and the two fractions. Conclusion We concluded that the protective effect of olive oil against oxidative damage induced by 2,4-D is mainly related to the antioxidant potential of its hydrophilic fraction.

Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

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Kojima, Misaki; Masui, Toshimitsu; Nemoto, Kiyomitsu; Degawa, Masakuni

2004-12-01

Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

Uptake and clearance of plutonium-238 from intact liver and liver cells transplanted into fat pads of F344/N rats

International Nuclear Information System (INIS)

Brooks, A.L.; Guilmette, R.A.; Hahn, F.F.; Jirtle, R.L.

1985-01-01

An understanding of the role of liver cells and the intact liver in plutonium biokinetics is needed. Liver cells were isolated from rats, injected into fat pads of recipient rats, and allowed 21 days to form cell colonies. Rats then received a single intraperitoneal injection of 1 μCi 238 Pu-citrate and were serially sacrificed. Uptake, retention, and distribution of Pu in intact liver and in liver cells growing in fat pads were determined. Intact liver cells took up about twice as much 238 Pu as liver cells transplanted into fat pads. However, the retention kinetics of Pu were similar for both the liver cells in the fat pads and the intact liver cells when the retention was expressed as activity per cell. 4 references, 1 figure, 1 table

Inhibitory Activities of Zygophyllum album: A Natural Weight-Lowering Plant on Key Enzymes in High-Fat Diet-Fed Rats

Science.gov (United States)

Mnafgui, Kais; Hamden, Khaled; Ben Salah, Hichem; Kchaou, Mouna; Nasri, Mbarek; Slama, Sadok; Derbali, Fatma; Allouche, Noureddine; Elfeki, Abdelfattah

2012-01-01

Obesity is a serious health problem that increased risk for many complications, including diabetes and cardiovascular disease. The results showed EZA, which found rich in flavonoids and phenolic compounds, exhibited an inhibitory activity on pancreatic lipase in vitro with IC50 of 91.07 μg/mL. In vivo administration of this extract to HFD-rats lowered body weight and serum leptin level; and inhibited lipase activity of obese rats by 37% leading to notable decrease of T-Ch, TGs and LDL-c levels accompanied with an increase in HDL-c concentration in serum and liver of EZA treated HFD-rats. Moreover, the findings revealed that EZA helped to protect liver tissue from the appearance of fatty cysts. Interestingly, supplementation of EZA modulated key enzyme related to hypertension such as ACE by 36% in serum of HFD animals and improve some of serum electrolytes such as Na+, K+, Cl−, Ca2+ and Mg2+. Moreover, EZA significantly protected the liver-kidney function by reverted back near to normal the values of the liver-kidney dysfunction indices AST&ALT, ALP, CPK and GGT activities, decreased T-Bili, creat, urea and uric acid rates. In conclusion, these results showed a strong antihypelipidemic effect of EZA which can delay the occurrence of dislipidemia and hypertension. PMID:23258993

Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

DEFF Research Database (Denmark)

Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

2013-01-01

-specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats.

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Sheen, Jiunn-Ming; Chen, Yu-Chieh; Hsu, Mei-Hsin; Tain, You-Lin; Huang, Ying-Hsien; Tiao, Mao-Meng; Li, Shih-Wen; Huang, Li-Tung

2016-08-20

Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.

High regenerative capacity of the liver and irreversible injury of male reproductive system in carbon tetrachloride-induced liver fibrosis rat model.

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Bubnov, Rostyslav V; Drahulian, Maria V; Buchek, Polina V; Gulko, Tamara P

2018-03-01

Liver fibrosis (LF) is a chronic disease, associated with many collateral diseases including reproductive dysfunction. Although the normal liver has a large regenerative capacity the complications of LF could be severe and irreversible. Hormone and sex-related issues of LF development and interactions with male reproductive have not been finally studied. The aim was to study the reproductive function of male rats in experimental CCl 4 -induced liver fibrosis rat model, and the capability for restoration of both the liver and male reproduction system. Studies were conducted on 20 3-month old Wistar male rats. The experimental animals were injected with freshly prepared 50% olive oil solution of carbohydrate tetrachloride (CCl 4 ). On the 8th week after injection we noted the manifestations of liver fibrosis. The rats were left to self-healing of the liver for 8 weeks. All male rats underwent ultrasound and biopsy of the liver and testes on the 8th and 16th weeks. The male rats were mated with healthy females before CCl 4 injection, after modeling LF on the 8th week, and after self-healing of the liver. Pregnancy was monitored on ultrasound. On the 8th week of experiment we observed ultrasound manifestation of advanced liver fibrosis, including hepatosplenomegaly, portal hypertension. Ultrasound exam of the rat testes showed testicular degeneration, hydrocele, fibrosis, scarring, petrifications, size reduction, and restriction of testicular descent; testes size decreased from 1.24 ± 0.62 ml to 0.61 ± 0.13, p  reproductive system and altering of fertility: the offspring of male rats with advanced LF was 4.71 ± 0.53 born alive vs 9.55 ± 0.47 born from mating with healthy males, p  reproductive system.

TRANSPLANTATION OF CRYOPRESERVED FETAL LIVER CELLS SEEDED INTO MACROPOROUS ALGINATE-GELATIN SCAFFOLDS IN RATS WITH LIVER FAILURE

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D. V. Grizay

2015-01-01

Full Text Available Aim. To study the therapeutic potential of cryopreserved fetal liver cells seeded into macroporous alginategelatin scaffolds after implantation to omentum of rats with hepatic failure.Materials and methods.Hepatic failure was simulated by administration of 2-acetyl aminofl uorene followed partial hepatectomy. Macroporous alginate-gelatin scaffolds, seeded with allogenic cryopreserved fetal liver cells (FLCs were implanted into rat omentum. To prevent from colonization of host cells scaffolds were coated with alginate gel shell. Serum transaminase activity, levels of albumin and bilirubin as markers of hepatic function were determined during 4 weeks after failure model formation and scaffold implantation. Morphology of liver and scaffolds after implantation were examined histologically. Results. Macroporous alginate-gelatin scaffolds after implantation to healthy rats were colonized by host cells. Additional formation of alginate gel shell around scaffolds prevented the colonization. Implantation of macroporous scaffolds seeded with cryopreserved rat FLCs and additionally coated with alginate gel shell into omentum of rats with hepatic failure resulted in signifi cant improvement of hepatospecifi c parameters of the blood serum and positive changes of liver morphology. The presence of cells with their extracellular matrix within the scaffolds was confi rmed after 4 weeks post implantation.Conclusion. The data above indicate that macroporous alginate-gelatin scaffolds coated with alginate gel shell are promising cell carriers for the development of bioengineered liver equivalents.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

Science.gov (United States)

Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

2017-09-21

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

Science.gov (United States)

Kandasamy, Neelamegam; Ashokkumar, Natarajan

2014-09-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats. Copyright © 2014 Elsevier Inc. All rights reserved.

MATERNAL HEMOLYSIS, ELEVATED LIVER-ENZYMES AND LOW PLATELETS SYNDROME - SPECIFIC PROBLEMS IN THE NEWBORN

NARCIS (Netherlands)

EELTINK, CM; VANLINGEN, RA; AARNOUDSE, JG; DERKS, JB; OKKEN, A

To evaluate the effects of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome on the fetus and neonate we retrospectively investigated the outcome of 87 pregnancies. All women showed thrombocytopenia, elevated liver enzymes and haemolysis. None of them died. Nine infants

Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

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Douglas Carvalho Caixeta

Full Text Available Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.

Incubation of 14C-trichloroethylene vapor with rat liver microsomes: uptake of radioactivity and covalent protein binding of metabolites

International Nuclear Information System (INIS)

Bolt, H.M.; Wolowski, L.; Buchter, A.; Bolt, W.; Gil, D.L.

1977-01-01

Microsomal uptake irreversible protein binding of labelled trichloroehtylene was measured following incubation with rat liver microsomes in an all-glass vacuum system. If the cofactor for oxidative metabolism, NADPH, is not added, the gaseous trichloroethylene rapidly equilibrates with the microsomal suspension. Addition of NADPH results in a further uptake of 14 C-trichloroethylene from the gas phase, linearly with time, which is due to enzymic metabolism. This part of uptake is inhibited by some arylimidazoles and 1.2.3-benzothiadiazoles. The compounds of greatest inhibitory potency were 6-chloro-1.2.3-benzothiadiazole and 5.6-dimethyl-1.2.3-benzothiadiazole. Part of the metabolites of 14 C-trichloroethylene formed by rat liver microsomes were irreversibly bound to microsomal protein, amounting up to 1 nmol per mg microsomal protein per hour. Model experiments on uptake of 14 C-trichloroethylene from the gas phase by albumin solutions and liposomal suspensions (from lecithin) showed a rapid equilibration of trichloroethylene also with these systems. Comparison with previous analogous data on vinyl chloride revealed an about 10 times higher affinity of trichloroethylene to albumin and lipid, consistent with the behaviour of both compounds in the rat liver microsomal system. (orig.) [de

Changes in the acinar distribution of some enzymes involved in carbohydrate metabolism in rat liver parenchyma after experimentally induced cholestasis

NARCIS (Netherlands)

van Noorden, C. J.; Frederiks, W. M.; Aronson, D. C.; Marx, F.; Bosch, K.; Jonges, G. N.; Vogels, I. M.; James, J.

1987-01-01

Extrahepatic cholestasis induced by ligation and transsection of the common bile duct caused a change in the parenchyma/stroma relationship in rat liver. Two weeks after ligation, the periportal zones of the parenchyma were progressively invaded by expanding bile ductules with surrounding connective

Gene expression for peroxisome-associated enzymes in hepatocellular carcinomas induced by ciprofibrate, a hypolipidemic compound

International Nuclear Information System (INIS)

Rao, M.S.; Nemali, M.R.; Reddy, J.K.

1986-01-01

Administration of hypolipidemic compounds leads to marked proliferation of peroxisomes and peroxisome-associated enzymes (PAE) in the livers of rodents and non-rodent species. The increase peroxisome-associated enzymes such as fatty acid β-oxidation system and catalase is shown to be due to an increase in the levels of mRNA. In this experiment they have examined hepatocellular carcinomas (HCC), induced in male F-344 rats by ciprofibrate (0.025%, w/w for 60 weeks), for gene expression of PAE. Total RNA was purified from HCC as well as from control and ciprofibrate (0.025% for 2 weeks) fed rat livers. Northern blot analysis was performed using [32/sub p/]cDNA probes for albumin, fatty acetyl-CoA oxidase, enoyl-CoA hydratase 3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and catalase. mRNA levels in HCC for albumin, fatty acid β-oxidation enzymes and catalase were comparable with those levels observed in the livers of rats given ciprofibrate for 2 weeks. In control livers the mRNAs for β-oxidation enzymes were low. Albumin mRNA levels in all the 3 groups were comparable. Additional studies are necessary to determine whether the increased level of mRNAs for the β-oxidation enzymes in HCC is due to the effect of ciprofibrate or to the gene amplification

Regulation by carbohydrate and clofibric acid of palmitoyl-CoA chain elongation in the liver of rats.

Science.gov (United States)

Kudo, Naomi; Toyama, Tomoaki; Mitsumoto, Atsushi; Kawashima, Yoichi

2003-05-01

Regulation of palmitoyl-CoA chain elongation (PCE) and its contribution to oleic acid formation were investigated in rat liver in comparison with stearoyl-CoA desaturase (SCD). Hepatic PCE activity was induced by the administration of 20% wt/vol glucose or fructose in the drinking water of normal rats. In streptozotocin-induced diabetic rats, the activities of both PCE and SCD were suppressed, and fructose, but not glucose, feeding caused an increase in the activities of both enzymes. Treatment of normal rats with clofibric acid in combination with carbohydrate further increased PCE, but not SCD, activity. FA analysis of hepatic lipids revealed that the proportion of oleic acid (18:1 n-9) increased upon administration of carbohydrate or clofibric acid. The treatment of rats with clofibric acid in combination with carbohydrate greatly increased the proportion of 18:1 n-9. A significant correlation was observed between PCE activity and the hepatic proportion of 18:1 n-9 (r2 = 0.874, P 0.05). Taken together, these results suggest that carbohydrate induces PCE as well as SCD activity to increase the hepatic 18:1 content in rat liver, and the increased PCE activity seems to be responsible for the further increase in 18:1 n-9 when carbohydrate is administered in combination with clofibric acid.

Influence of Thyroxine on Blood Parameters and Liver Enzymes

African Journals Online (AJOL)

Dr Olaleye

control group of twelve adult rats (six females and six males) received feed and water ... energy expenditure through actions on protein, carbohydrate and lipid metabolism. With specific regard to liver lipid metabolism, thyroid hormones.

A comparative study on the hepatoprotective action of bear bile and Coptidis Rhizoma aqueous extract on experimental liver fibrosis in rats.

Science.gov (United States)

Wang, Ning; Feng, Yibin; Cheung, Fan; Chow, Oi-Yee; Wang, Xuanbin; Su, Weiwei; Tong, Yao

2012-11-29

Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Coptidis Rhizoma Aqueous Extract (CRAE), berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.

Duodenal-jejunal bypass surgery up-regulates the expression of the hepatic insulin signaling proteins and the key regulatory enzymes of intestinal gluconeogenesis in diabetic Goto-Kakizaki rats.

Science.gov (United States)

Sun, Dong; Wang, Kexin; Yan, Zhibo; Zhang, Guangyong; Liu, Shaozhuang; Liu, Fengjun; Hu, Chunxiao; Hu, Sanyuan

2013-11-01

Duodenal-jejunal bypass (DJB), which is not routinely applied in metabolic surgery, is an effective surgical procedure in terms of type 2 diabetes mellitus resolution. However, the underlying mechanisms are still undefined. Our aim was to investigate the diabetic improvement by DJB and to explore the changes in hepatic insulin signaling proteins and regulatory enzymes of gluconeogenesis after DJB in a non-obese diabetic rat model. Sixteen adult male Goto-Kakizaki rats were randomly divided into DJB and sham-operated groups. The body weight, food intake, hormone levels, and glucose metabolism were measured. The levels of protein expression and phosphorylation of insulin receptor-beta (IR-β) and insulin receptor substrate 2 (IRS-2) were evaluated in the liver. We also detected the expression of key regulatory enzymes of gluconeogenesis [phosphoenoylpyruvate carboxykinase-1 (PCK1), glucose-6-phosphatase-alpha (G6Pase-α)] in small intestine and liver. DJB induced significant diabetic improvement with higher postprandial glucagons-like peptide 1, peptide YY, and insulin levels, but without weight loss. The DJB group exhibited increased expression and phosphorylation of IR-β and IRS-2 in liver, up-regulated the expression of PCK1 and G6Pase-α in small intestine, and down-regulated the expression of these enzymes in liver. DJB is effective in up-regulating the expression of the key proteins in the hepatic insulin signaling pathway and the key regulatory enzymes of intestinal gluconeogenesis and down-regulating the expression of the key regulatory enzymes of hepatic gluconeogenesis without weight loss. Our study helps to reveal the potential role of hepatic insulin signaling pathway and intestinal gluconeogenesis in ameliorating insulin resistance after metabolic surgery.

Measurement of peroxisomal enzyme activities in the liver of brown trout (Salmo trutta, using spectrophotometric methods

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Resende Albina D

2003-03-01

Full Text Available Abstract Background This study was aimed primarily at testing in the liver of brown trout (Salmo trutta spectrophotometric methods previously used to measure the activities of catalase and hydrogen peroxide producing oxidases in mammals. To evaluate the influence of temperature on the activities of those peroxisomal enzymes was the second objective. A third goal of this work was the study of enzyme distribution in crude cell fractions of brown trout liver. Results The assays revealed a linear increase in the activity of all peroxisomal enzymes as the temperature rose from 10° to 37°C. However, while the activities of hydrogen peroxide producing oxidases were strongly influenced by temperature, catalase activity was only slightly affected. A crude fraction enriched with peroxisomes was obtained by differential centrifugation of liver homogenates, and the contamination by other organelles was evaluated by the activities of marker enzymes for mitochondria (succinate dehydrogenase, lysosomes (aryl sulphatase and microsomes (NADPH cytochrome c reductase. For peroxisomal enzymes, the activities per mg of protein (specific activity in liver homogenates were strongly correlated with the activities per g of liver and with the total activities per liver. These correlations were not obtained with crude peroxisomal fractions. Conclusions The spectrophotometric protocols originally used to quantify the activity of mammalian peroxisomal enzymes can be successfully applied to the study of those enzymes in brown trout. Because the activity of all studied peroxisomal enzymes rose in a linear mode with temperature, their activities can be correctly measured between 10° and 37°C. Probably due to contamination by other organelles and losses of soluble matrix enzymes during homogenisation, enzyme activities in crude peroxisomal fractions do not correlate with the activities in liver homogenates. Thus, total homogenates will be used in future seasonal and

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

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Kandasamy, Neelamegam; Ashokkumar, Natarajan, E-mail: npashokkumar1@gmail.com

2014-09-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

International Nuclear Information System (INIS)

Kandasamy, Neelamegam; Ashokkumar, Natarajan

2014-01-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

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Haider Raza

2015-02-01

Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

The effects of storage on the retention of enzyme activity in cryostat sections. A quantitative histochemical study on rat liver

NARCIS (Netherlands)

Frederiks, W. M.; Ouwerkerk, I. J.; Bosch, K. S.; Marx, F.; Kooij, A.; van Noorden, C. J.

1993-01-01

The effect of storage of unfixed cryostat sections from rat liver for 4 h, 24 h, 3 days and 7 days at -25 degrees C was studied on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, xanthine oxidoreductase, glutamate dehydrogenase, succinate dehydrogenase (all demonstrated

Effect of D-tagatose on liver weight and glycogen content of rats.

Science.gov (United States)

Bär, A; Lina, B A; de Groot, D M; de Bie, B; Appel, M J

1999-04-01

D-tagatose is an incompletely absorbed ketohexose (stereoisomer of D-fructose) which has potential as an energy-reduced alternative sweetener. In an earlier 90-day toxicity study, rats fed diets with 10, 15 and 20% D-tagatose exhibited increased liver weights, but no histopathological alterations. To determine whether there might be any toxicological relevance to this effect, three studies were conducted in male, adult Sprague-Dawley rats. In the first study, four groups received Purina diet (group A), Purina diet with 20% D-tagatose (group B), SDS diet (group C), or SDS diet with 20% D-tagatose (group D). For groups A and B, the 28-day treatment period was followed by a 14-day recovery period (Purina diet). Food remained available to all animals until the time of sacrifice. Groups of 10 rats were killed on days 14 (groups A and B), 28 (groups A-D), and 42 (groups A and B). Body weights, as well as weights of wet and lyophilized livers, were determined. The lyophilized livers collected on day 28 from groups A and B were analyzed for protein, total lipid, glycogen, DNA, and residual moisture. By day 14, relative wet liver weights had increased by 23% in group B. On day 28, the increase was 38% in group B and 44% in group D. At the end of the recovery period, the increase had diminished to 14% in group B. On day 28, liver glycogen content (in %) was significantly increased, and liver protein, lipid, and DNA contents were significantly decreased in group B compared to group A. Total amounts per liver of protein, total lipid, glycogen, and DNA were significantly increased. In the second study, four groups of 20 rats each received SDS diet with 0, 5, 10, and 20% D-tagatose for 29-31 days. The food was available until the time of sacrifice. At termination, plasma was obtained from 10 rats/group for clinicochemical analyses. Five rats/group were subjected to whole-body perfusion, followed by processing of livers for qualitative and quantitative electron microscopic

Mangosteen peel extract reduces formalin-induced liver cell death in rats

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Afiana Rohmani

2014-08-01

Full Text Available Background Formalin is a xenobiotic that is now commonly used as a preservative in the food industry. The liver is an organ that has the highest metabolic capacity as compared to other organs. Mangosteen or Garcinia mangostana Linn (GML peel contains xanthones, which are a source of natural antioxidants. The purpose of this study was to evaluate the effect of mangosteen peel extract on formalin-induced liver cell mortality rate and p53 protein expression in Wistar rats. Methods Eighteen rats received formalin orally for 2 weeks, and were subsequently divided into 3 groups, consisting of the formalin-control group receiving a placebo and treatment groups 1 and 2, which were treated with mangosteen peel extract at doses of 200 and 400 mg/kgBW/day, respectively. The treatment was carried out for 1 week, and finally the rats were terminated. The differences in liver cell mortality rate and p53 protein expression were analyzed. Results One-way ANOVA analysis showed significant differences in liver cell mortality rate among the three groups (p=0.004. The liver cell mortality rate in the treatment group receiving 400 mg/kgBW/day extract was lower than that in the formalin-control group. There was no p53 expression in all groups. Conclusions Garcinia mangostana Linn peel extract reduced the mortality rate of liver cells in rats receiving oral formalin. Involvement of p53 expression in liver cell mortality in rats exposed to oral formalin is presumably negligible.

Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

Science.gov (United States)

Fairchild, C R; Ivy, S P; Rushmore, T; Lee, G; Koo, P; Goldsmith, M E; Myers, C E; Farber, E; Cowan, K H

1987-11-01

We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.

The Effects of Gardeniae Fructus Aqua-Acupuncture on Liver Injury of Rats Induced by CCI4 (

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Park, Hee-Soo

2000-12-01

Full Text Available This is the study of the effects of Aqua-acupuncture with Gardeniae Fructus on thc recovery of rat's liver which was damaged by 0.3ml/ea of CCI4. Rats were divided into 4 groups; Normal-group(None treated group, Control-group(Not treated after CCI4-intoxicated, Exp. I(Treated with Saline Aqua-acupuncture after CCI4-intoxicated and Exp. ll(Treated with Gardeniae Fructus Aqua-acupuncture after CCI4-intoxicated. Biochemical assays for each serum enzyme activities of AST, ALT, Albumin, LDH, γ-GT, TG and Total cholesterol were performed. The results were summarized as follows: 1. AST activities in serum significantly decreased in the Gardeniae Fructus Aqua-acupuncture treated group after CCI4-intoxicated. In companson with Saline-treated group after CCI4-intoxicated, the Gardeniae Fructus Aqua-acupuncture treated group *The professor of Dept. of Acupuncture & Moxibustion, 2. At T activities in serum significantly decreased in the Gardeniae Fructus Aqua-acupuncture treated group after CCI4-intoxicated. In com pan son with Saline-treated group after CCI4-intoxicated, the Gardeniae Fructus Aqua-acupuncture treated group after CCI4-intoxicated worked effectively to rat's damaged liver. 3. Albumin in serum increased in the Gardeniae Fructus Aqua-acupurkture treated group after CCI4-intoxicated. 4. LDH in serum significantly decreased in the Gardeniae Fructus Aqua-acupuncture treated group after CCI4-intoxicated. In comparison with Saline-treated group after CClcintox icated, the Gardeniae Fructus Aqua acupuncture treated group after CCI4-intoxicated worked highly effectively to rat's damaged liver. 5. γ-GT In serum significantly decreased In the Gardeniae Fructus Aqua-acupuncture trea ted group after CCI4-intoxicated. In compan son with Saline-treated group after CCI4-intoxicated, the Crardeniae Fructus Aqua-acupuncture treated group after CCI4-intoxicated was not recognized significantly. 6. TG in serum significantly decreased in the Gardeniae Fructus

A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)

DEFF Research Database (Denmark)

Leeming, Diana Julie; He, Y.; Veidal, S. S.

2011-01-01

A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) an...

Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

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Matthew J Robertson

Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

Yinchenhao Decoction Ameliorates Alpha-Naphthylisothiocyanate Induced Intrahepatic Cholestasis in Rats by Regulating Phase II Metabolic Enzymes and Transporters

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Ya-Xiong Yi

2018-05-01

Full Text Available Yinchenhao Decoction (YCHD, a famous traditional Chinese formula, has been used for treating cholestasis for 1000s of years. The cholagogic effect of YCHD has been widely reported, but its pharmacodynamic material and underlying therapeutic mechanism remain unclear. By using ultra-high-performance liquid chromatography (UHPLC-quadrupole time-of-flight mass spectrometry, 11 original active components and eight phase II metabolites were detected in rats after oral administration of YCHD, including three new phase II metabolites. And it indicated that phase II metabolism was one of the major metabolic pathway for most active components in YCHD, which was similar to the metabolism process of bilirubin. It arouses our curiosity that whether the metabolism process of YCHD has any relationship with its cholagogic effects. So, a new method for simultaneous quantitation of eight active components and four phase II metabolites of rhein, emodin, genipin, and capillarisin has been developed and applied for their pharmacokinetic study in both normal and alpha-naphthylisothiocyanate (ANIT-induced intrahepatic cholestasis rats. The results indicated the pharmacokinetic behaviors of most components of YCHD were inhibited, which was hypothesized to be related to different levels of metabolic enzymes and transporters in rat liver. So dynamic changes of intrahepatic enzyme expression in cholestasis and YCHD treated rats have been monitored by an UHPLC-tandem mass spectrometry method. The results showed expression levels of UDP-glucuronosyltransferase 1-1 (UGT1A1, organic anion-transporting polypeptide 1A4 (OATP1A4, multidrug resistance-associated protein 2 (MRP2, multidrug resistance protein 1, sodium-dependent taurocholate cotransporter, and organic anion-transporting polypeptide 1A2 were significantly inhibited in cholestasis rats, which would account for reducing the drug absorption and the metabolic process of YCHD in cholestatic rats. A high dose (12 g/kg of

Effect of irradiation on gene expression of rat liver adhesion molecules. In vivo and in vitro studies

International Nuclear Information System (INIS)

Moriconi, Federico; Malik, Ihtzaz; Ahmad, Ghayyor; Dudas, Joszef; Ramadori, Giuliano; Rave-Fraenk, Margret; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

2009-01-01

Background and purpose: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro. Material and methods: Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology. Results: Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), β 1 -integrin, β 2 -integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, β 1 -integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), β 2 -integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-)α, interleukin-(IL-)1β, or IL-6 plus TNF-α led to an upregulation of P-selectin, ICAM-1 and VCAM-1. Conclusion: The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of inflammation in the irradiated rat liver. (orig.)

Hepatic injury after whole-liver irradiation in the rat

International Nuclear Information System (INIS)

Geraci, J.P.; Jackson, K.L.; Mariano, M.S.; Leitch, J.M.

1985-01-01

Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD/sub 50/30/ day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [ 131 I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

Science.gov (United States)

2012-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. Methods Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. Results Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. Conclusions These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver. PMID:22569330

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

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Zhang Bei

2012-05-01

Full Text Available Abstract Background Nonalcoholic fatty liver disease (NAFLD is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC extracted from Acaudina molpadioides in fatty liver rats. Methods Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT and aspartate aminotransferase (AST activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. Results Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS, malic enzyme (ME and glucose-6-phosphatedehydrogenase (G6PDH were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP activity was observed in SCC-feeding rats. Conclusions These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.

Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

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Sayed M. Mizar

2015-03-01

Full Text Available Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg and/or chrysin (25 mg/kg by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT and aspartate transaminase (AST, as well as hepatic Myeloperoxidase (MPO, total nitrate (NOx, glutathione (GSH and liver malondialdehyde (MDA were measured at the end of the experiment. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS subtypes, endothelial (eNOS and inducible (iNOS in liver samples were assessed by Western blotting and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

Evaluation of antioxidant activity of grapevine leaves extracts (Vitis labrusca in liver of Wistar rats

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THAYS K. SCHAFFER

2016-03-01

Full Text Available The aim of this study was to evaluate the hepatoprotection of organic and conventional grapevine leaves extract (Vitis labrusca. The total polyphenol content and the isolate polyphenols by HPLC were evaluate. The animals received intraperitoneal injections of saline or extracts (conventional or organic - 30 mg/kg for 14 days. On day 15, the rats received carbon tetrachloride (CCl4 or mineral oil (i.p.. After 4h, the animals were euthanized. The analysis of the liver enzymes activity (AST, ALT, GGT was performed using serum, obtained by blood and the levels of lipid peroxidation (TBARS, protein oxidation (carbonyl, and the activity of antioxidant enzymes superoxide dismutase and catalase were analyzed in the liver. The results showed that the organic extract is richer in polyphenol and resveratrol than the conventional one. Both extracts prevent lipid peroxidation and protein oxidation generated by CCl4. Moreover, the extracts demonstrated ability to modulate the activity of SOD and CAT, as well as to establish a balance in the ratio of SOD/CAT. We also found that the CCl4 increased the levels of AST and GGT, and that both extracts prevent this. These results indicate that grapevine leaves extracts, both, organic and conventional, can prevent liver disorders.

Action of ionizing radiation on catalase synthesis in the rat liver

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Komov, V.P.; Strelkova, M.A.

1975-01-01

3-amino-1,2,4-triazole was used to study the effect of total-body X-ray irradiation on the rates of catalase synthesis and breakdown in rat liver. It was found that in the interval between hour 22 and hour 144 of radiation sickness, the average rate of catalase synthesis in the liver was 2.6 times lower in rats that received a dose of 800 rads than in control rats

Metallothionein expression during liver regeneration after partial hepatectomy in cadmium-pretreated rats

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Margeli, A.P. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Theocharis, S.E. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Yannacou, N.N. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Spiliopoulou, C. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Koutselinis, A. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece))

1994-10-01

Metallothionein is a low molecular mass protein inducible mainly by heavy metals, having high affinity for binding cadmium, zinc and copper. In the present study we investigated the expression of metallothionein in regenerating liver, at different time intervals, in cadmium pretreated partially hepatectomized rats. Liver metallothionein is highly expressed during regeneration induced by partial hepatectomy in rats, providing zinc within the rapidly growing tissue. Cadmium pretreatment caused inhibition of the first peak of liver regeneration, while metallothionein expression was markedly more prominent in the liver residues of cadmium-pretreated rats. These results demonstrate that although metallothionein able to bind temporarily metal ions as zinc and cadmium has been highly expressed, the liver regenerative process was inhibited possibly due to the effects of cadmium on other pivotal events necessary to the DNA replication. (orig.)

Isolating Lysosomes from Rat Liver.

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Pryor, Paul R

2016-04-01

This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays. © 2016 Cold Spring Harbor Laboratory Press.

Structural and ultrastructural study of rat liver influenced by electromagnetic radiation.

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Holovská, K; Almášiová, V; Cigánková, V; Beňová, K; Račeková, E; Martončíková, M

2015-01-01

Mobile communication systems are undoubtedly an environmental source of electromagnetic radiation (EMR). There is an increasing concern regarding the interactions of EMR with the humans. The aim of this study was to examine the effects of EMR on Wistar rat liver. Mature rats were exposed to electromagnetic field of frequency 2.45 GHz and mean power density of 2.8 mW/cm2 for 3 h/d for 3 wk. Samples of the liver were obtained 3 h after the last irradiation and processed histologically for light and transmission electron microscopy. Data demonstrated the presence of moderate hyperemia, dilatation of liver sinusoids, and small inflammatory foci in the center of liver lobules. Structure of hepatocytes was not altered and all described changes were classified as moderate. Electron microscopy of hepatocytes revealed vesicles of different sizes and shapes, lipid droplets, and proliferation of smooth endoplasmic reticulum. Occasionally necrotizing hepatocytes were observed. Our observations demonstrate that EMR exposure produced adverse effects on rat liver.

Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

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D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

2013-05-01

Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

Protective function of complement against alcohol-induced rat liver damage.

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Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

2004-11-01

The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

Contribution of liver alcohol dehydrogenase to metabolism of alcohols in rats.

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Plapp, Bryce V; Leidal, Kevin G; Murch, Bruce P; Green, David W

2015-06-05

The kinetics of oxidation of various alcohols by purified rat liver alcohol dehydrogenase (ADH) were compared with the kinetics of elimination of the alcohols in rats in order to investigate the roles of ADH and other factors that contribute to the rates of metabolism of alcohols. Primary alcohols (ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol) and diols (1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol) were eliminated in rats with zero-order kinetics at doses of 5-20 mmol/kg. Ethanol was eliminated most rapidly, at 7.9 mmol/kgh. Secondary alcohols (2-propanol-d7, 2-propanol, 2-butanol, 3-pentanol, cyclopentanol, cyclohexanol) were eliminated with first order kinetics at doses of 5-10 mmol/kg, and the corresponding ketones were formed and slowly eliminated with zero or first order kinetics. The rates of elimination of various alcohols were inhibited on average 73% (55% for 2-propanol to 90% for ethanol) by 1 mmol/kg of 4-methylpyrazole, a good inhibitor of ADH, indicating a major role for ADH in the metabolism of the alcohols. The Michaelis kinetic constants from in vitro studies (pH 7.3, 37 °C) with isolated rat liver enzyme were used to calculate the expected relative rates of metabolism in rats. The rates of elimination generally increased with increased activity of ADH, but a maximum rate of 6±1 mmol/kg h was observed for the best substrates, suggesting that ADH activity is not solely rate-limiting. Because secondary alcohols only require one NAD(+) for the conversion to ketones whereas primary alcohols require two equivalents of NAD(+) for oxidation to the carboxylic acids, it appears that the rate of oxidation of NADH to NAD(+) is not a major limiting factor for metabolism of these alcohols, but the rate-limiting factors are yet to be identified. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of the effects of nafenopin, methyl clofenapate, WY-14,643 and clofibric acid on peroxisome proliferation and replicative DNA synthesis in rat liver

International Nuclear Information System (INIS)

Price, R.J.; Evans, J.G.; Lake, B.G.; Gangolli, S.D.

1991-01-01

A wide variety of chemicals have been shown to produce hepatic peroxisome proliferation (PP) in the rat and certain of these compounds are also hepatocarcinogens. In this study the authors have investigated the relationship between PP and cell replication in the rat liver. Male Sprague-Dawley rats were fed control diet or diet containing either 0.0125 and 0.05% nafenopin (NAF), 0.05% methyl clofenapate (MC), 0.025% Wy-14,643 (WY) or 0.5% clofibric acid (CA) for 1 and 15 wk. All four compounds produced marked liver enlargement and a sustained induction of peroxisomal (palmitoyl-CoA oxidation) and microsomal (lauric acid 12-hydroxylase) fatty acid oxidizing enzyme activities. Enzyme induction was less marked with 0.0125% NAF than with 0.05% NAF which was similar to that produced by the other three compounds. Replicative DNA synthesis was studied by implanting 7 day Alzet osmotic pumps containing [ 3 H]thymidine during wk 0-1 and 14-15. After 1 wk replicative DNA synthesis (assessed as radioactivity incorporated into homogenate DNA by scintillation counting) was increased in all treatment groups to 170-325% of control levels. Hepatocyte Labelling Index (determined by autoradiography of liver sections) was increased in all treated groups. After 15 wk hepatic DNA radioactivity levels were 155 and 200% of control in MC and WY treated rats, respectively, whereas NAF and CA had no effect. These results demonstrate that the relationship between the magnitude of PP and induction of cell replication depends on the compound being studied and that some peroxisome proliferators produce sustained stimulation of replicative DNA synthesis in the rat

Mechanism of liver lipid accumulation in X-irradiated rat

International Nuclear Information System (INIS)

Aiyar, A.S.; De, A.K.

1978-01-01

The incorporation, both in vivo and in vitro, of 14 C-acetate into hepatic lipids, notably the triglyceride and free fatty acid fractions, is greatly reduced following whole-body irradiation and is indicative of significantly reduced lipogenesis. Irradiation results in a several-fold increase in fatty acid oxidation, by the liver in vitro as well as in the whole animal, during the phase of active hepatic lipid accumulation. Small increases in lipoprotein lipase activity of adipose, immediately following irradiation and up to 24 hours, and the attendant marked fall in adipose lipids are suggestive of increased mobilization of peripheral lipids during the early period. However, in view of the fact that maximum lipid accumulations occurs very much later, inflow of extra-hepatic lipid into liver does not appear to be of major etiological significance. There is three-fold experimental evidence in support of an impairment of trigylceride transport from liver being primarily responsible for the build-up of liver lipids: (I) Triton WR-1339 induced hypertriglyceridemia is totally absent in the irradiated rat during the period when liver lipids increase significantly; (II) the rate of disappearance of radioactivity from pre-labeled hepatic lipids is considerably lower in the irradiated rats; and (III) the irradiated rats show decrease in lipoproteins of liver cell-sap and of serum, the latter being more marked and a lowered synthesis of the lipoproteins, as assessed by labeling of the protein moiety. (orig.) [de

Mechanism of liver lipid accumulation in X-irradiated rat

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Aiyar, A S; De, A K [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

1978-03-01

The incorporation, both in vivo and in vitro, of /sup 14/C-acetate into hepatic lipids, notably the triglyceride and free fatty acid fractions, is greatly reduced following whole-body irradiation and is indicative of significantly reduced lipogenesis. Irradiation results in a several-fold increase in fatty acid oxidation, by the liver in vitro as well as in the whole animal, during the phase of active hepatic lipid accumulation. Small increases in lipoprotein lipase activity of adipose, immediately following irradiation and up to 24 hours, and the attendant marked fall in adipose lipids are suggestive of increased mobilization of peripheral lipids during the early period. However, in view of the fact that maximum lipid accumulations occurs very much later, inflow of extra-hepatic lipid into liver does not appear to be of major etiological significance. There is three-fold experimental evidence in support of an impairment of trigylceride transport from liver being primarily responsible for the build-up of liver lipids: (I) Triton WR-1339 induced hypertriglyceridemia is totally absent in the irradiated rat during the period when liver lipids increase significantly; (II) the rate of disappearance of radioactivity from pre-labeled hepatic lipids is considerably lower in the irradiated rats; and (III) the irradiated rats show decrease in lipoproteins of liver cell-sap and of serum, the latter being more marked and a lowered synthesis of the lipoproteins, as assessed by labeling of the protein moiety.

Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism.

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Briley-Saebo, Karen C; Johansson, Lars O; Hustvedt, Svein Olaf; Haldorsen, Anita G; Bjørnerud, Atle; Fayad, Zahi A; Ahlstrom, Haakan K

2006-07-01

We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.

Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

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Wei Zhang

2014-01-01

Full Text Available Background and Aim. Thiazolidinediones (TZDs can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH. Angiotensin (Ang II, the primary effector of renin-angiotensin system (RAS, plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD, pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

Hepatocyte transplants improve liver function and encephalopathy in portacaval shunted rats.

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Fogel, Wieslawa Agnieszka; Stasiak, Anna; Maksymowicz, Michał; Kobos, Jozef; Unzeta, Mercedes; Mussur, Miroslaw

2014-07-01

Rats with portacaval shunt (PCS) are useful experimental models of human hepatic encephalopathy in chronic liver dysfunction. We have previously shown that PCS modifies amine neurotransmitter systems in the CNS and increases voluntary alcohol intake by rats. Hepatocyte transplantation, used in acute liver failure, has recently also been applied to chronic liver diseases, which prompted us to investigate whether the altered brain amine system and the drinking behavior in long-term shunted rats could be normalized by hepatocyte transplants. Hepatocytes, isolated from syngeneic donors by collagenase digestion, were injected (3 × 10(6) cells/rat) into the pancreatic tail region, 6 months after PCS. Hepatic function was evaluated by measuring urine urea and plasma L-histidine concentrations. A free choice test with two bottles (tap water and 10% ethyl alcohol) was performed for 3 days to assess the rats' preference for alcohol. The rats were euthanized 2 months posttransplantation. Brain histamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured by radioenzymatic assay and by HPLC-EC, respectively, N-tele-methylhistamine by GC/MS while MAOA and MAOB activities by isotopic procedures. Portacaval shunt rats with hepatocyte transplants gave more urea than before transplantation, with lower plasma L-His levels and higher body weight versus the PCS counterparts. Also, those rats consumed less alcohol. The CNS amines and 5-HIAA concentrations, as well as MAO-B activity, being abnormally high in untreated PCS rats, significantly reduced after PCS hepatocyte treatment. The results support the therapeutic values of hepatocyte transplants in chronic liver diseases and the temporary character of PCS-exerted CNS dysfunctions. © 2014 John Wiley & Sons Ltd.

Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease.

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Ganji, Shobha H; Kukes, Gary D; Lambrecht, Nils; Kashyap, Moti L; Kamanna, Vaijinath S

2014-02-15

Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage, comprises a spectrum of liver abnormalities including the early fat deposition in the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin decreases plasma triglycerides, but its effect on hepatic steatosis is elusive. To examine the effect of niacin on steatosis, rats were fed either a rodent normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin in the diet for 4 wk. For regression studies, rats were first fed the HF diet for 6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the diet) while on the HF diet for 6 wk. The findings indicated that inclusion of niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat content, liver weight, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA expression of fatty acid synthesis or oxidation genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a key enzyme in triglyceride synthesis. These novel findings suggest that niacin effectively prevents and causes the regression of experimental hepatic steatosis. Approved niacin formulation(s) for other indications or niacin analogs may offer a very cost-effective opportunity for the clinical development of niacin for treating NAFLD and fatty liver disease.

Sirolimus influence on hepatectomy-induced liver regeneration in rats

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Edimar Leandro Toderke

Full Text Available OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered by resection of 70% of the liver of adult rats. METHODS: we used 40 Wistar rats randomly divided into two groups (study and control, each group was divided into two equal subgroups according to the day of death (24 hours and seven days. Sirolimus was administered at a dose of 1mg/kg in the study group and the control group was given 1 ml of saline. The solutions were administered daily since three days before hepatectomy till the rats death to removal of the regenerated liver, conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was measured by the KWON formula, by thenumber of mitotic figures (hematoxylin-eosin staining and by the immunohistochemical markers PCNA and Ki-67. RESULTS: there was a statistically significant difference between the 24h and the 7d groups. When comparing the study and control groups in the same period, there was a statistically significant variation only for Ki-67, in which there were increased numbers of hepatocytes in cell multiplication in the 7d study group compared with the 7d control group (p = 0.04. CONCLUSION: there was no negative influence of sirolimus in liver regeneration and there was a positive partial effect at immunohistochemistry with Ki-67.

Study in radiation tolerance of damaged liver induced by dimethylaminoazobenzene. Histological study using Wistar rats

International Nuclear Information System (INIS)

Izumiyama, Kazutaka; Kodama, Akihisa; Kono, Michio

1997-01-01

We studied to determine the tolerable dose of radiation in damaged liver using Wistar male rats aged 4 weeks. A damaged liver group fed on low-protein animal chow containing 0.07% dimethylaminoazobenzene (DAB) ad libitum. Rats feeding on the chow without DAB served as the normal liver group. In both groups, two rats each underwent irradiation of the right half of the liver with doses of 5 Gy, 10 Gy, 15 Gy, or 20 Gy using a 15 MeV electron beam. The animals were sacrificed 2 or 4 weeks after irradiation, and the irradiated and non-irradiated parts of the liver were compared histologically with respect to hepatocellular necrosis, the extent of degeneration, and the degree of inflammatory cell infiltration, as well as the degree of inflammatory cell infiltration and fibrosis in Glisson's capsule. Secondly, in the normal liver group, 6 rats were irradiated with dose of 20 Gy, and in the damaged liver group, 6 rats each were irradiated with doses of 10 Gy, 12 Gy, 15 Gy or 20 Gy, and the same study was performed. In the normal liver group, no histological differences were seen between the irradiated and non-irradiated parts of the liver even when irradiated with 20 Gy dose. In the damaged liver group, there were no differences between the irradiated and non-irradiated parts of the liver in animals given 15 Gy or 10 Gy. In the 12 Gy group, however, one out of three rats each showed more severe changes in the irradiated part at 2 and 4 weeks after irradiation. One out of six rats in the 15 Gy group and four out of six rats in the 20 Gy group died in the first week after irradiation. In the damaged liver group, a single irradiation of up to 10 Gy delivered to one half of the liver was tolerable. At doses of 12 Gy or higher, however, irreversible changes occurred in some animals, and deaths occurred at 15 Gy or 20 Gy. Since even 20 Gy was tolerated in the normal liver group, damaged liver showed a lower tolerance than normal liver. (author)

Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

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Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

2006-03-01

Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

Energy Technology Data Exchange (ETDEWEB)

Perocco, Paolo [Department of Experimental Pathology, Cancerology Section, viale Filopanti 22, I-40126, University of Bologna, Bologna (Italy); Bronzetti, Giorgio [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy); Canistro, Donatella; Sapone, Andrea; Affatato, Alessandra; Pozzetti, Laura; Broccoli, Massimiliano [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Valgimigli, Luca [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Pedulli, Gian Franco [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Iori, Renato [C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Barillari, Jessica [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy)]|[C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Sblendorio, Valeriana [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Legator, Marvin S. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States); Paolini, Moreno [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Abdel-Rahman, Sherif Z. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States)]. E-mail: sabdelra@utmb.edu

2006-03-20

Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard.

Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

International Nuclear Information System (INIS)

Perocco, Paolo; Bronzetti, Giorgio; Canistro, Donatella; Valgimigli, Luca; Sapone, Andrea; Affatato, Alessandra; Pedulli, Gian Franco; Pozzetti, Laura; Broccoli, Massimiliano; Iori, Renato; Barillari, Jessica; Sblendorio, Valeriana; Legator, Marvin S.; Paolini, Moreno; Abdel-Rahman, Sherif Z.

2006-01-01

Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard

Establishment of animal model of dual liver transplantation in rat.

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Ying Zhang

Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

Cistanche tubulosa ethanol extract mediates rat sex hormone levels by induction of testicular steroidgenic enzymes.

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Wang, Tian; Chen, Chen; Yang, Man; Deng, Baiwan; Kirby, Gordon Michael; Zhang, Xiaoying

2016-01-01

Plants of the genus Cistanche Hoffmg. et Link (Orobanchaceae) are usually used as ethno-medicine in Eastern Asia. Pharmacology studies have shown that Cistanche possesses an androgen-like effect; however, the exact mechanism is unclear. The present study determines the effect of ethanol extract of Cistanche tubulosa (Schenk) R. Wight stem (CTE) on hormone levels and testicular steroidogenic enzymes in rats. Phenylethanoid glycoside content of CTE was detected by UV spectrophotometry. Rats were fed with different doses of CTE (0.2, 0.4, and 0.8 g/kg) by intragastric administration for 20 d. Sperm parameters were measured by staining and counting method. The level of progesterone and testosterone in serum was quantified by radioimmunoassay. The expression levels of cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase/17, 20-lyase (CYP17A1), and a liver metabolic enzyme (CYP3A4) in the microsome were assessed by immunohistochemical staining or/and western blot analysis. The study illustrates that the administration of CTE (0.4 and 0.8 g/kg) increased sperm count (2.3- and 2.7-folds) and sperm motility (1.3- and 1.4-folds) and decreased the abnormal sperm (0.76- and 0.6-folds). The serum level of progesterone and testosterone in rats was also increased by CTE administration (p blot analysis confirmed that the expression of CYP11A1, CYP17A1, and CYP3A4 was enhanced by CTE (p < 0.05). It was also found that high-dose of CTE can cause mild hepatic edema. Our results suggest that the increase in sex hormone levels could be mediated by the induction of testicular steroidogenic enzymes.

Free methionine supplementation limits alcohol-induced liver damage in rats

DEFF Research Database (Denmark)

Parlesak, Alexandr; Bode, C.; Bode, J.C.

1998-01-01

Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accu...

Role of liver nerves and adrenal medulla in glucose turnover of running rats

DEFF Research Database (Denmark)

Sonne, B; Mikines, K J; Richter, Erik

1985-01-01

Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had...... identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control...... rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats...

Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

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Noeman Saad A

2011-08-01

Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats.

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Hirose, Akihiko; Yamazaki, Tohru; Sakamoto, Takeshi; Sunaga, Katsuyoshi; Tsuda, Tadashi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [¹⁴C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [¹⁴C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [¹⁴C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.

Hypoglycemic and Hypolipidemic Effects of the Cracked-Cap Medicinal Mushroom Phellinus rimosus (Higher Basidiomycetes) in Streptozotocin-Induced Diabetic Rats.

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Rony, Kuttikkadan A; Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Phellinus rimosus is a parasitic host specific polypore mushroom with profound antioxidant, antihepatotoxic, anti-inflammatory, antitumor, and antimutagenic activities. This study investigated the hypoglycemic and hypolipidemic activities of the wood-inhabiting polypore mushroom Ph. Rimosus in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (45 mg/kg) to Wistar rats. The effects of 30 days treatment with Ph. Rimosus (50 and 250 mg/ kg) and glibenclamide (0.65 mg/kg) on blood glucose level, serum insulin, serum lipid profile, liver glycogen, liver function enzymes, and non-enzymic and enzymic antioxidants activities in pancreas, liver, and kidney were evaluated in STZ-induced diabetic rats. Oral administration of Ph. Rimosus extract exhibited a significant reduction in blood glucose, triacylglycerol, total cholesterol, LDL-cholesterol, and liver function enzymes, and increased serum insulin, liver glycogen, and HDL-cholesterol levels in STZ-induced diabetic rats. Furthermore, Ph. Rimosus treatment increased antioxidant status in pancreas, liver, and kidney tissues with concomitant decreases in levels of thiobarbituric acid- reactive substances. Results of this study indicated that Ph. Rimosus possessed significant hypoglycemic and hypolipidemic activities and this effect may be related to its insulinogenic and antioxidant effect.

Short-term hepatic effects of depleted uranium on xenobiotic and bile acid metabolizing cytochrome P450 enzymes in the rat

International Nuclear Information System (INIS)

Gueguen, Y.; Souidi, M.; Baudelin, C.; Dudoignon, N.; Grison, S.; Dublineau, I.; Marquette, C.; Voisin, P.; Gourmelon, P.; Aigueperse, J.

2006-01-01

The toxicity of uranium has been demonstrated in different organs, including the kidneys, skeleton, central nervous system, and liver. However, few works have investigated the biological effects of uranium contamination on important metabolic function in the liver. In vivo studies were conducted to evaluate its effects on cytochrome P450 (CYP) enzymes involved in the metabolism of cholesterol and xenobiotics in the rat liver. The effects of depleted uranium (DU) contamination on Sprague-Dawley were measured at 1 and 3 days after exposure. Biochemical indicators characterizing liver and kidney functions were measured in the plasma. The DU affected bile acid CYP activity: 7α-hydroxycholesterol plasma level decreased by 52% at day 3 whereas microsomal CYP7A1 activity in the liver did not change significantly and mitochondrial CYP27A1 activity quintupled at day 1. Gene expression of the nuclear receptors related to lipid metabolism (FXR and LXR) also changed, while PPARα mRNA levels did not. The increased mRNA levels of the xenobiotic-metabolizing CYP3A enzyme at day 3 may be caused by feedback up-regulation due to the decreased CYP3A activity at day 1. CAR mRNA levels, which tripled on day 1, may be involved in this up-regulation, while mRNA levels of PXR did not change. These results indicate that high levels of depleted uranium, acting through modulation of the CYP enzymes and some of their nuclear receptors, affect the hepatic metabolism of bile acids and xenobiotics. (orig.)

Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

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Jiamin Zhang

Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

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Osmers, R G; Schütz, E; Diedrich, F; Wehry, B; Krauss, T; Oellerich, M; Kuhn, W

1998-02-01

Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.

[Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].

Science.gov (United States)

Liu, Xu-hua; Chen, Yu; Wang, Tai-ling; Lu, Jun; Zhang, Li-jie; Song, Chen-zhao; Zhang, Jing; Duan, Zhong-ping

2007-10-01

To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure. We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

Effect of Salvia miltiorrhiza Bge extract on liver cirrhosis in rats | Li ...

African Journals Online (AJOL)

Purpose: To explore the effects of Salvia miltiorrhiza Bge.extract(SMBE) on diethylnitrosamine(DEN)- induced liver cirrhosis in rats. Methods: SMBE was obtained by extracting dried Salvia miltiorrhiza Bge. in water. Liver cirrhosis was induced in Wistar rats by injecting diethylnitrosamine in abdominal cavity once a week for ...

Subcellular distribution of styrene oxide in rat liver

International Nuclear Information System (INIS)

Pacifici, G.M.; Cuoci, L.; Rane, A.

1984-01-01

The subcellular distribution of ( 3 H)-styrene-7,8-oxide was studied in the rat liver. The compound was added to liver homogenate to give a final concentration of 2 X 10(-5); 2 X 10(-4) and 2 X 10(-3) M. Subcellular fractions were obtained by differential centrifugation. Most of styrene oxide (59-88%) was associated with the cytosolic fraction. Less than 15 percent of the compound was retrieved in each of the nuclear, mitochondrial and microsomal fractions. A considerable percentage of radioactivity was found unextractable with the organic solvents, suggesting that styrene oxide reacted with the endogenous compounds. The intracellular distribution of this epoxide was also studied in the perfused rat liver. Comparable results with those previously described were obtained. The binding of styrene oxide to the cytosolic protein was investigated by equilibrium dialysis and ultrafiltration. Only a small percentage of the compound was bound to protein

Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome

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Udenze Ifeoma Christiana

2015-01-01

Full Text Available Aims and objectives: The aim of this study is to determine the plasma levels of the liver enzymes alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT, and lactate dehydrogenase (LDH in people with metabolic syndrome and to determine the association between the liver enzymes and obesity, insulin resistance, interleukin 6 (IL-6, and C-reactive protein (CRP in adult Nigerians with metabolic syndrome. Materials and Methods: This was a case control study of 50 adult men and women with metabolic syndrome, and 50 age- and sex-matched males and females without metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Program (NCEP-Adult Treatment Panel III (ATPIII criteria. Written informed consent was obtained from the participants. Sociodemographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an overnight fast. The ethics committee of the Lagos University Teaching Hospital in Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the student′s t-test. Regression and correlation analysis were used to determine the associations between variables. Statistical significance was set at P < 0.05. Results: There was a statistically significant increase in the liver enzymes ALP (P = 0.031, ALT (P = 0.019, and GGT (P = 0.037, as well as in the inflammatory markers CRP (P = 0.019 and the cytokine IL-6 (P = 0.040 between the two study groups. ALP and ALT showed significant correlation with waist circumference, BMI, fasting insulin, and waist/hip ratio (P < 0.05. Multivariate regression also identified ALT, AST, and ALP to be associated with IL-6 and CRP (P < 0.05. Conclusion: Liver enzyme levels were increased in metabolic syndrome and associated with obesity, fasting insulin, and CRP. Elevated liver enzymes may indicate dysmetabolism and increased

Aqueous calyxes extract of Roselle or Hibiscus sabdariffa Linn supplementation improves liver morphology in streptozotocin induced diabetic rats.

Science.gov (United States)

Nazratun Nafizah, Akhtar Husin; Budin, Siti Balkis; Zaryantey, Abd Hamid; Mariati, Abd Rahman; Santhana, Raj Louis; Osman, Mohamad; Muhd Hanis, Md Idris; Jamaludin, Mohamed

2017-03-01

The complex series of deleterious events among diabetes patients leads to multiple organ failure. Therefore, a holistic approach of treatment is urgently required to prevent worsening of complications. The present investigation was carried out to study the possible protective effects of Roselle or Hibiscus sabdariffa Linn (HSL) calyxes aqueous extract, as an antidiabetic and antioxidant agent against oxidative liver injury in streptozotocin-induced diabetic rats. A single dose of streptozotocin (45mg/kg body weight, iv) was used to induced diabetes in male Sprague Dawley rats which were then divided into two groups: Diabetic control (DC) and HSL-treated diabetic (DR) group. Normal rats were divided into normal control (NC), HSL-treated control (NR). Aqueous calyxes extract of HSL (100mg/kg/day, orally) was given for 28 consecutive days in the treated group. Weight, biochemical and histopathological (light and electron microscopic) parameters were compared in all groups. Supplementation of HSL significantly lowered the level of fasting blood glucose and increased plasma insulin level in DR group compared to DC group (p<0.05). Alanine aminotransaminases and aspartate aminotransferase enzymes level were found to be significantly reduced in DR compared to DC. Microscopic examination demonstrated destruction of the liver architecture, cytoplasmic vacuolation of the hepatocytes and signs of necrosis in diabetic rats. Moreover, dilatation and congestion of blood vessels with leucocytes adherence were detected. Ultrastructural study using electron microscope showed homogeneous substance accumulation in nuclear chromatin, a decrease of organelles and mitochondrial degeneration in the diabetic rats. Administration of HSL in diabetic rats causes significant decrease in hepatocyte destruction and prevented the changes associated with the diabetic condition. Thus, our findings provide a scientific rationale for the use of HSL as promising agent in preventing liver injury in

Time-course of cadmium-induced acute hepatotoxicity in the rat liver: the role of apoptosis

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Tzirogiannis, Konstantinos N.; Panoutsopoulos, Georgios I.; Hereti, Rosa I.; Alexandropoulou, Katerina N.; Basayannis, Aristidis C.; Mykoniatis, Michael G. [Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., 115 27, Athens (Greece); Demonakou, Maria D. [Histopathology Laboratory, Sismanoglion G.D. Hospital, Sismanogliou 1, Marousi, Attiki 151 27 (Greece)

2003-12-01

Exposure to toxic metals and pollutants is a major environmental problem. Cadmium is a metal causing acute hepatic injury but the mechanism of this phenomenon is poorly understood. In the present study, we investigated the mechanism and time-course of cadmium-induced liver injury in rats, with emphasis being placed on apoptosis in parenchymal and nonparenchymal liver cells. Cadmium (3.5 mg/kg body weight) was injected intraperitoneally and the rats were killed 0, 9, 12, 16, 24, 48 and 60 h later. The extent of liver injury was evaluated for necrosis, apoptosis, peliosis, mitoses and inflammatory infiltration in hematoxylin-eosin-stained liver sections, and by assaying serum enzyme activities. The number of cells that died via apoptosis was quantified by TUNEL assay. The identification of nonparenchymal liver cells and activated Kupffer cells was performed histochemically. Liver regeneration was evaluated by assaying the activity of liver thymidine kinase and by the rate of {sup 3}H-thymidine incorporation into DNA. Both cadmium-induced necrotic cell death and parenchymal cell apoptosis showed a biphasic elevation at 12 and 48 h and peaked at 48 and 12 h, respectively. Nonparenchymal cell apoptosis peaked at 48 h. Peliosis hepatis, another characteristic form of liver injury, was first observed at 16 h and, at all time points, closely correlated with the apoptotic index of nonparenchymal liver cells, where the lesion was also maximial at 48 h. Kupffer cell activation and neutrophil infiltration were minimal for all time points examined. Based on thymidine kinase activity, liver regeneration was found to discern a classic biphasic peak pattern at 12 and 48 h. It was very interesting to observe that cadmium-induced liver injury did not involve inflammation at any time point. Apoptosis seems to be a major mechanism for the removal of damaged cells, and constitutes the major type of cell death in nonparenchymal liver cells. Apoptosis of nonparenchymal cells is the basis

Liver polyribosome distribution in intact and adrenalectomized rats exposed to. gamma. radiation

Energy Technology Data Exchange (ETDEWEB)

Yatvin, M B; Abdel-Halim, M N [Wisconsin Univ., Madison (USA). Dept. of Radiology; Wisconsin Univ., Madison (USA). Dept. of Human Oncology)

1978-06-01

The mechanism(s) by which gamma radiation influences liver polyribosome distribution was studied in groups of intact and adrenalectomized male rats. A shift from light to heavy aggregates occurred in the polyribosomes of both intact and adrenalectomized rats after they were exposed to gamma rays. In irradiated adrenalectomized rats, however, the shift to heavier aggregates was not as great as that which occurred in irradiated adrenal-intact animals. Subcutaneous injection of cortisone acetate (10 mg/100 g body weight) also altered the liver polyribosome patterns of both intact and adrenalectomized rats within 8 hours of its administration. The shift which occurred following cortisone administration, however, was less striking than that seen after irradiation only. Thus, although adrenal glucocorticoids contribute to the radiation-indu ied shift in liver polyribosomes in adrenal-intact rats, other factors appear to be involved, since the shift is also obtained in adrenalectomized animals.

Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

International Nuclear Information System (INIS)

Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

2013-01-01

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA

Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

Energy Technology Data Exchange (ETDEWEB)

Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

2013-11-15

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

The effect of radiation on processing of nuclear RNA and chromatin ribonuclease activity in rat liver and thymus

International Nuclear Information System (INIS)

Tokarskaya, V.I.; Skotnikova, O.I.; Umansky, S.R.

1975-01-01

The effect of radiation on the kinetics of nuclear RNA degradation was studied during actinomycin chase. The intranuclear breakdown of RNA in thymus was inhibited for the first 30 to 120 min after 800 R irradiation of rats. In liver the degradation of nuclear RNA was unchanged for 60 min after irradiation. By the second hour, the breakdown of the rRNA precursor accelerated and the processing of D-RNA slowed down. Rat thymus and liver chromatin showed RNAase activity with two optimal pH values - in the acidic (pH 5.0 to 5.5) and weakly alkaline (pH 7.5) regions. The activity of the acidic RNAase of thymus (but not the liver) chromatin fell after 5 to 20 kR irradiation in vitro. The activity of the alkaline RNAase did not change under these conditions. The data indicate that a fall in activity of the acidic RNAase in irradiated thymus chromatin may be related to disturbance in the enzyme-inhibitor interaction. A possible contribution of the chromatin acidic RNAase to the processing of nuclear RNA in control and after irradiation is discussed. (author)

Alkaline comet assay in liver and stomach, and micronucleus assay in bone marrow, from rats treated with 2-acetylaminofluorene, azidothymidine, cisplatin, or isobutyraldehyde.

Science.gov (United States)

Kraynak, A R; Barnum, J E; Cunningham, C L; Ng, A; Ykoruk, B A; Bennet, B; Stoffregen, D; Merschman, M; Freeland, E; Galloway, S M

2015-07-01

As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM) initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined the ability of the assay to determine the genotoxicity of 2-acetylaminofluorene (AAF), azidothymidine (AZT), cisplatin (CPN), and isobutyraldehyde (IBA) in liver and glandular stomach of male Sprague-Dawley rats. Rats were given oral doses of test compound or control once daily for three days. High dose levels were approximately maximum tolerated doses and were based on preliminary range-finding studies. Tissues were harvested 3h after the final dose (48h after the initial dose). A bone marrow micronucleus assay (MN) was also conducted on the rats treated with AZT, CPN, and IBA. Acute toxic effects of treatment were determined primarily through histomorphologic analysis of liver and stomach but also by body weight and serum liver enzyme changes. The comet assay was conducted on fresh tissue preparations but frozen samples from two studies were also assayed. Statistically significant dose-related differences in comet % DNA in tail were found in liver and stomach for the genotoxin AZT and in liver for the genotoxin CPN, but not in liver or stomach for the non-genotoxin IBA. Statistically significant differences in % DNA in tail were measured in liver for the low and mid dose of the genotoxin AAF, but not the high dose. The comet assays of frozen liver suspensions from CPN- and AAF-treated rats yielded comparable results to the assays of fresh preparations. There were no indications of significant toxicity induced by any treatment. The micronucleus assay was positive for CPN and AZT and negative for IBA. In conclusion, the in vivo comet assay is capable of detecting genotoxic effects of a variety of chemicals and may fill an important role in the genotoxicity test battery. Copyright © 2015 Elsevier B.V. All rights reserved.

Superoxide Dismutase (SOD Enzyme Activity Assay in Fasciola spp. Para-sites and Liver Tissue Extract

Directory of Open Access Journals (Sweden)

M Assady

2011-09-01

Full Text Available Background: The purpose of this comparative study was to detect superoxide dismutase (SOD activities in Fasciola hepatica, F. gigantica parasites, infected and healthy liver tissues in order to determine of species effects and liver infection on SODs activity level.Methods: Fasciola spp. parasites and sheep liver tissues (healthy and infected liver tissues, 10 samples for each, were collected, homogenized and investigated for protein measurement, protein detection and SOD enzyme activity assay. Protein concentration was measured by Bradford method and SODs band protein was detected on SDS-PAGE. SODs activity was determined by iodonitrotetrazolium chloride, INT, and xanthine substrates. Independent samples t-test was conducted for analysis of SODs activities difference.Results: Protein concentration means were detected for F. hepatica 1.3 mg/ ml, F. gigantica 2.9 mg/ml, healthy liver tissue 5.5 mg/ml and infected liver tissue 1.6 mg/ml (with similar weight sample mass. Specific enzyme activities in the samples were obtained 0.58, 0.57, 0.51, 1.43 U/mg for F. hepatica, F. gigantica, healthy liver and infected liver respectively. Gel electrophoresis of Fasciola spp. and sheep liver tissue extracts revealed a band protein with MW of 60 kDa. The statistical analysis revealed significant difference between SOD activities of Fasciola species and also between SOD activity of liver tissues (P<.05.Conclusion: Fasciola species and liver infection are effective causes on SOD enzyme activity level.

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

Energy Technology Data Exchange (ETDEWEB)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); Alegret, Marta; Merlos, Manuel; Roglans, Nuria [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain; Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain); IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain); CIBERobn, [Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain

2011-02-15

: >Fructose administration as a liquid solution to Sprague-Dawley male rats induced hypertriglyceridemia, hyperleptinemia, hepatic steatosis and necroinflammation. >Atorvastatin administration: >Abolished histological sings of necroinflammation and reduced plasma and liver triglyceride concentrations. >Reduced the expression of phospho-I{kappa}B >Reduced the expression of fructokinase, a key enzyme controlling fructose metabolism

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

International Nuclear Information System (INIS)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.; Alegret, Marta; Merlos, Manuel; Roglans, Nuria; Laguna, Juan C.

2011-01-01

��Fructose administration as a liquid solution to Sprague-Dawley male rats induced hypertriglyceridemia, hyperleptinemia, hepatic steatosis and necroinflammation. →Atorvastatin administration: →Abolished histological sings of necroinflammation and reduced plasma and liver triglyceride concentrations. →Reduced the expression of phospho-IκB →Reduced the expression of fructokinase, a key enzyme controlling fructose metabolism

Sweet potato Ipomoea Batatas Modulates Radiation-induced Oxidative damage in Liver and kidney of Male Albino Rats

International Nuclear Information System (INIS)

Darwish, M. M.; Farag, M. F. S.; Osman, N. N.

2010-01-01

Sweet potato Ipomoea Batatas, one of the major vegetable crops consumed worldwide, is rich in phytochemicals, which displayed antioxidant activities. This work aims at assessing the radio-protective properties of sweet potato tubers on liver and kidney tissues. Male albino rats were whole body exposed to 0.5 Gy day after day for a period of 20 days. Animal received orally prepared aqueous extract of sweet potato tubers (100 mg kg/body weight), one week before irradiation and during the period of radiation exposure. The results demonstrated that irradiation of rats induced a significant increase in lipid peroxides level measured as thiobarbituric acid reactive substances (TBARS) concomitant with a significant decrease in superoxide dismutase (SOD), and catalase (CAT) activity and glutathione (GSH) content in liver and kidney tissues. Administration of a freshly prepared aqueous extract of sweet potato tubers to rats, one week pre-irradiation and during the period of radiation exposure has significantly of ameliorated the oxidative stress in both tissues. The significant amelioration in oxidative stress was substantiated by improvement of liver and kidney enzymes Treatment of rats with sweet potato has significantly reduced the increase in serum alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase (LDH) activity, serum creatinine and urea levels. Furthermore, hyperglycemia and alteration in lipid profile manifested by a significant increase in triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), and a significant decrease in high density lipoprotein cholesterol (HDL-C), were improved in sweet potato-treated irradiated rats compared to those only irradiated. According to the results obtained in the present study, it could be concluded that sweet potato through its antioxidant activities could protect cellular membrane from radiation induced oxidative damage in animals and preserve the

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

NARCIS (Netherlands)

Berg, van den G.J.; de Goeij, J.J.M.; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendriks, H.F.J.

1991-01-01

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (<1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

NARCIS (Netherlands)

Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

1991-01-01

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

Age dependence of rat liver function measurements

DEFF Research Database (Denmark)

Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

1989-01-01

Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

Metabolite kinetics: formation of acetaminophen from deuterated and nondeuterated phenacetin and acetanilide on acetaminophen sulfation kinetics in the perfused rat liver preparation

International Nuclear Information System (INIS)

Pang, K.S.; Waller, L.; Horning, M.G.; Chan, K.K.

1982-01-01

The role of hepatic intrinsic clearance for metabolite formation from various precursors on subsequent metabolite elimination was was investigated in the once-through perfused rat liver preparation. Two pairs of acetaminophen precursors: [ 14 C] phenacetin-d5 and [ 3 H] phenacetin-do, [ 14 C] acetanilide and [ 3 H] phenacetin were delivered by constant flow (10 ml/min/liver) either by normal or retrograde perfusion to the rat liver preparations. The extents of acetaminophen sulfation were compared within the same preparation. The data showed that the higher the hepatocellular activity (intrinsic clearance) for acetaminophen formation, the greater the extent of subsequent acetaminophen sulfation. The findings were explained on the basis of blood transit time and metabolite duration time. Because of blood having only a finite transit time in liver, the longer the drug requires for metabolite formation, the less time will remain for metabolite sulfation and the less will be the degree of subsequent sulfation. Conversely, when the drug forms the primary metabolite rapidly, a longer time will remain for the metabolite to be sulfated in liver to result in a greater degree of metabolite sulfation. Finally, the effects of hepatic intrinsic clearances for metabolite formation and zonal distribution of enzyme systems for metabolite formation and elimination in liver are discussed

Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

Directory of Open Access Journals (Sweden)

Yumin Xu

Full Text Available Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF.Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations.Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats.sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.

Science.gov (United States)

Ayyar, Vivaswath S; Almon, Richard R; DuBois, Debra C; Sukumaran, Siddharth; Qu, Jun; Jusko, William J

2017-05-08

Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL). Data mining identified 451 differentially regulated proteins. These proteins were analyzed on the basis of temporal regulation, cellular localization, and literature-mined functional information. Of the 451 proteins, 378 were clustered into six functional groups based on major clinically-relevant effects of CS in liver. MPL-responsive proteins were highly localized in the mitochondria (20%) and cytosol (24%). Interestingly, several proteins were related to hepatic stress and signaling processes, which appear to be involved in secondary signaling cascades and in protecting the liver from CS-induced oxidative damage. Consistent with known adverse metabolic effects of CS, several rate-controlling enzymes involved in amino acid metabolism, gluconeogenesis, and fatty-acid metabolism were altered by MPL. In addition, proteins involved in the metabolism of endogenous compounds, xenobiotics, and therapeutic drugs including cytochrome P450 and Phase-II enzymes were differentially regulated. Proteins related to the inflammatory acute-phase response were up-regulated in response to MPL. Functionally-similar proteins showed large diversity in their temporal profiles, indicating complex mechanisms of regulation by CS. Clinical use of corticosteroid (CS) therapy is frequent and chronic. However, current knowledge on the proteome-level effects of CS in liver and

Immunohistochemical analysis of cannabinoid receptor 1 expression in steatotic rat livers.

Science.gov (United States)

Zduniak, Krzysztof; Ziółkowski, Piotr; Regnell, Pontus; Tollet-Egnell, Petra; Åkesson, Lina; Cooper, Martin E

2016-04-01

The primary aim of the present study was to determine the expression levels of cannabinoid receptor type 1 (CB1) in steatotic rat livers. The secondary aim was to clarify whether steatosis and inflammation are more marked in areas with increased CB1 overexpression. For ethical and economic reasons, the present study investigated tissue from archived liver blocks, which were obtained from 38 rats that had been euthanized during the course of previous research at the Karolinska Institute of the Karolinska University Hospital (Stockholm, Sweden) and Lund University (Malmö, Sweden). Liver tissue fixed in formalin and embedded in paraffin was used that had been sourced from 36 male Sprague Dawley rats (age, 7 weeks) and 2 rats (age, 180 days) lacking normal leptin receptors. The rat liver tissue was stained with antibodies against CB1 and counterstained with hematoxylin. The expression of CB1 and the number of cells overexpressing CB1 were determined. Steatosis was scored according to the Dixon scoring system. CB1 overexpression and steatosis were detected in hepatocytes from all 38 livers sampled. The expression of CB1 was more marked in hepatocytes localized next to portal triads. Near the central veins, the expression was significantly weaker. Steatosis was more marked in areas of increased CB1 overexpression. Lymphocyte infiltration was more commonly observed in areas of increased CB1 overexpression. Therefore, the present results indicate that CB1 receptors are overexpressed in areas with steatosis, and indicate that CB1 in hepatocytes contributes to the formation of steatosis in rats, even prior to its progression to steatohepatitis. These results are consistent with publications reporting that CB1 in hepatocytes increases lipogenesis and contributes to inflammation.

Subcellular localization of pituitary enzymes

Science.gov (United States)

Smith, R. E.

1970-01-01

A cytochemical procedure is reported for identifying subcellular sites of enzymes hydrolyzing beta-naphthylamine substrates, and to study the sites of reaction product localization in cells of various tissues. Investigations using the substrate Leu 4-methoxy-8-naphthylamine, a capture with hexonium pararosaniline, and the final chelation of osmium have identified the hydrolyzing enzyme of rat liver cells; this enzyme localized on cell membranes with intense deposition in the areas of the parcanaliculi. The study of cells in the anterior pituitary of the rat showed the deposition of reaction product on cell membrane; and on the membranes of secretion granules contained within the cell. The deposition of reaction product on the cell membrane however showed no increase or decrease with changes in the physiological state of the gland and release of secretion granules from specific cells.

Study on Biochemical Indices of Liver Function Tests of Albino Rats ...

African Journals Online (AJOL)

bilirubin, ALT (in rats fed with palm and groundnut oil-based diet), AST (in rats fed with coconut ... These results therefore, indicate a compromise in liver of rats administered 10% oil - based diet. ..... medicinal plants II: Effects of Aplotaxis lappa.

Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

Science.gov (United States)

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

2016-04-01

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

Establishment of a rat model of early-stage liver failure and Th17/Treg imbalance

OpenAIRE

LI Dong; LU Zhonghua; GAN Jianhe

2016-01-01

ObjectiveTo investigate the methods for establishing a rat model of early-stage liver failure and the changes in Th17, Treg, and Th17/Treg after dexamethasone and thymosin interventions. MethodsA total of 64 rats were randomly divided into carbon tetrachloride (CCl4) group and endotoxin ［lipopolysaccharide (LPS)］/D-galactosamine (D-GalN) combination group to establish the rat model of early-stage liver failure. The activities of the rats and changes in liver function and whole blood Th17 and ...

Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine

International Nuclear Information System (INIS)

Ramanathan, R.; Misra, U.K.

1976-01-01

The effect of administration of cystamine (5 mg/100 g body weight) before 1,200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32 P-radioactivity (counts/min/μmole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH 2 32 PO 4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U- 14 C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U- 14 C)glucose into liver triglycerides and phosphoglycerides of control rats. (orig.) [de

Polyploidization delay in rat hepatocytes under liver growth inhibition by hypokinesia

Science.gov (United States)

Faktor, V. M.; Malyutin, V. F.; Li, S. Y.; Brodskiy, V. Y.

1981-01-01

A study of young rats, weighing 55 to 59 g, after being for 10 days in conditions of limited mobility, shows a retardation of body growth as well as that of liver growth. The decrease in the rate of growth is accompanied by a reduction of cell proliferation and by delay polyploidization of hepatocytes in the liver of experimental rats. The materials, methods, and results of research are discussed.

High expression of liver histone deacetylase 3 contributes to high-fat-diet-induced metabolic syndrome by suppressing the PPAR-γ and LXR-α-pathways in E3 rats.

Science.gov (United States)

Li, Dongmin; Wang, Xuan; Ren, Wuchao; Ren, Juan; Lan, Xi; Wang, Feimiao; Li, Hongmin; Zhang, Fujun; Han, Yan; Song, Tianbao; Holmdahl, Rikard; Lu, Shemin

2011-09-15

In the previous experiment, we found that there was a different response between E3 rats and DA.1U rats to high-fat-diet-induced metabolic syndrome (HFD-MetS). The aim of this study was to explore the cause and molecular mechanism of the genetic difference in susceptibility to metabolic syndrome in E3 rats as compared with DA.1U rats. Firstly, a 12-week HFD-MetS model in E3 and DA.1U rats was carried out and assessed. Then, the expression of key insulin signaling molecules, metabolic nuclear receptors, metabolic key enzymes and histone deacetylases (Hdacs) was determined by different methods. Finally, the effects of overexpression and disruption of Hdac3 on metabolic nuclear receptors were analyzed in CBRH-7919 cells and primarily-hepatic cells from DA.1U and E3 rats. We found that E3 rats were susceptible, while DA.1U rats were resisted to HFD-MetS. The expression of liver X receptor α,β (LXR-α,β), farnesoid X receptor (FXR), peroxisome proliferator activated receptor γ (PPAR-γ) and cholesterol 7α-hydroxylase (CYP7A1) increased markedly in DA.1U rat liver, whereas they decreased significantly in E3 rats. The expression of Hdac3 increased by HFD treatment in both E3 and DA.1U rat livers, but the constitutive Hdac3 expression was lower in DA.IU rat liver than in E3 rat liver. Importantly, overexpression of Hdac3 could downregulate the expression of LXR-α, PPAR-γ and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from DA.IU rats. On the contrary, disruption of Hdac3 by shRNA upregulated the expression of LXR-α, PPAR-γ and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from E3 rats. The results suggested that a high constitutive expression of Hdac3 inhibiting the expression of PPAR-γ, LXR-α and CYP7A1 in liver contributes to HFD-MetS in E3 rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

Science.gov (United States)

Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

2017-03-01

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

PPARα ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats

International Nuclear Information System (INIS)

Toyama, Tetsuya; Nakamura, Hideki; Harano, Yuichi; Yamauchi, Norihito; Morita, Atsuhiro; Kirishima, Toshihiko; Minami, Masahito; Itoh, Yoshito; Okanoue, Takeshi

2004-01-01

Oxidative stress is a major pathogenetic factor in hepatic fibrosis. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor which is known to affect oxidative stress and PPARα ligands may have rescue effects on hepatic fibrosis. We tested this hypothesis using rat thioacetamide (TAA) models of liver cirrhosis. Rats were given intraperitoneal injection of TAA and treated with a diet containing one of the two PPARα ligands, Wy-14,643 (WY) or fenofibrate. WY treatment dramatically reduced hepatic fibrosis and also prevented the inhibition catalase of mRNA expression caused by TAA. Correspondingly, catalase activity increased in the TAA + WY group but decreased in the control TAA group. The antifibrotic action of fenofibrate in the TAA model was comparable with that of WY. PPARα ligands have an antifibrotic action in the rat TAA model of liver cirrhosis, probably due to an antioxidant effect of enhanced catalase expression and activity in the liver

Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients.

Science.gov (United States)

Al-Jameil, Noura; Khan, Farah A; Arjumand, Sadia; Khan, Mohammad F; Tabassum, Hajera

2014-01-01

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is associated with dyslipidemia and disturbed liver function. Aim of the present work is to assess the liver enzymes and to find its association with hyperlipidemic profile in T2DM. Total of 157 subjects were studied and divided into two groups; diabetes (n=81) and non-diabetes (n=76). Various biochemical parameters like fasting glucose, post prandial glucose, HbA1c, total cholesterol (TC), triglycerides (Tg), high density lipoprotein cholesterol (HDL-C), alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transferase (GGT) were analyzed by ROCHE module Cobas 6000 (C501 & C601) analyzer, kits were procured by ROCHE diagnostics. Low density lipoprotein cholesterol (LDL-C) was estimated by Freidwald's formula. Statistical analysis was performed by applying student t test and Pearson's correlation coefficient, at 0.0001 and 0.05 level of significance, respectively. All the glycemic control parameters, lipid profile parameters except HDL-C and liver enzymes were found increased in diabetes group and significantly differ from non-diabetes group (p>0.0001). ALT showed significant positive correlation with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and GGT at p>0.05. AST showed very weak relation with all parameters while GGT was positively associated with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and ALT at p>0.05. In conclusion, T2DM incline to elevate liver enzymes, especially ALT and GGT were of significance. Routine screening of ALT and GGT in T2DM patients may assists early detection of liver abnormalities and to arrest the progress of disease.

Therapeutic effects of globular adiponectin in diabetic rats with nonalcoholic fatty liver disease.

Science.gov (United States)

Ma, Hong; Cui, Fan; Dong, Jing-Jing; You, Guo-Ping; Yang, Xiang-Jiu; Lu, Hua-Dong; Huang, Yan-Ling

2014-10-28

To explore the therapeutic role of globular adiponectin (gAd) in high-fat diet/streptozotocin (STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease (NAFLD). Seven rats were fed a basic diet (normal control group; NC) during the experiment. Experimental rats (14 rats) were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus (T2DM) and NAFLD. Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d (gAd-treated group), while the other 7 rats (T2DM/NAFLD group) received 0.9% saline. Plasma biochemical parameters and insulin concentrations were measured. Liver histopathology was examined by hematoxylin-eosin staining. Insulin receptor expression in the liver was analyzed by immunohistochemical staining, Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Compared to the control group, the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin. Plasma glucose and lipid levels were decreased in the gAd-treated group, while serum insulin levels increased. The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group, and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats. Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group (NAS 1.39 ± 0.51 vs 1.92 ± 0.51, P Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion, mediating glucolipid metabolism, regulating insulin receptor expression and alleviating hepatic steatosis.

Health behavior associated with liver enzymes among obese Korean adolescents, 2009-2014.

Science.gov (United States)

Lee, Eun-Young; Choi, Hwa Young; Cho, Hyunsoon; Kim, Bo Hyun; Ki, Moran

2018-01-01

Obesity is major risk factor for liver health. This study aimed to clarify whether specific health behaviors were associated with liver function in obese adolescents in Korea. Based on national school health examination data from 2009 to 2014, 25,142 obese or overweight students were examined for aspartate transaminase and alanine transaminase levels, and health behaviors. Multiple logistic regression was used to calculate the odds ratio for liver enzyme elevation. Subjects who thought of themselves as "very fat" had a 1.6 times higher odds ratio for liver enzyme elevations than those who thought of themselves as "normal." Those who consumed fast food 3 to 5 times weekly had 1.3 times higher odds ratio (OR = 1.27, 95% confidence interval = 1.05-1.54) for the elevation of ALT than those who did not consume fast food. Those who took sugar-sweetened beverage 3 to 5 times weekly had 1.2 times higher odds ratio (OR = 1.24, 95% confidence interval = 1.07-1.42) for the elevation of ALT than those who did not take it. Those who played computer game more than 2 hours a day showed 1.1 times higher odds ratio (OR = 1.10, 95% confidence interval = 1.01-1.21) for the elevation of ALT than those who did not. Specific food item and its frequency of consumption were identified for the positive and negative association with the elevation of liver enzymes. Self-image of body shape, sleeping time and need of help for alcohol or smoking problems also showed substantial association with the elevation.

Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

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Azadeh Nabizadeh Haghighi

2016-03-01

Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

Effect of strychnine hydrochloride on liver cytochrome P450 mRNA expression and monooxygenase activities in rat

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Qian Gao

2011-08-01

Full Text Available Strychnos nux-vomica L. has been frequently used in traditional Chinese medicine but has high acute toxicity. It is commonly taken with Glycyrrhizae radix to decrease its toxicity but the mechanism of this interaction is unknown. In this work, the mRNA expression and the activity of four cytochrome P450 (CYP enzymes representative of four subfamilies (CYP1A, CYP3A, CYP2C and CYP2E were determined ex vivo in rat livers from groups of Wistar rats orally administered strychnine hydrochloride (SH at three doses (0.1, 0.3 and 0.9 mg/kg/day alone and, at the highest dose, in combination with glycyrrhetinic acid (GA, 25 mg/kg/day or liquiritin (LQ, 20 mg/kg/day once a day for 7 consecutive days. Compared to control, the mRNA expressions of CYP3A1, 1A2 and 2E1 were higher in rats receiving the highest dose of SH but lower for CYP3A1 and CYP2E1 in rats receiving the SH+GA and SH+LQ combinations. CYP2E1 activity was higher and CYP2C, CYP3A and CYP1A2 activities were lower in rats receiving the highest dose of SH. In contrast CYP1A2 and CYP2C activities were higher and CYP2E1 and CYP3A activities lower in rats receiving the SH+GA combination. CYP2E1 and CYP3A activities were also lower in rats receiving the SH+LQ combination. The results show that treatment with SH for 7 days affects the expression and the activity of CYP enzymes and that coadministration of GA and LQ modulates these effects. This modulation may explain the role of Glycyrrhizae radix in reducing the acute toxicity of Strychnos nux-vomica L.CYPs enzymes.

Quantitative evaluation of 99mTc-GSA for fatty liver and ischemia-reperfusion injury in rats

International Nuclear Information System (INIS)

Kimoto, Mitsunori

1996-01-01

99m Tc-GSA (GSA) liver scintigraphy was performed in rats with fatty liver and ischemia-reperfusion injury to study the usefulness of GSA in evaluating these pathological processes. Fatty liver was produced by feeding rats a choline-deficient diet. The rats with fatty liver were divided into five groups according to the length of the diet (controls, two weeks, six weeks, 10 weeks, and 12 weeks). In the rats dieted for two weeks and six weeks, regional hepatic ischemia was also induced by clamping the left hepatic artery and the left portal vein for 10 minutes, then reperfusion was performed for 15 minutes. GSA was administered via the IVC. t 90 , or the time at which the liver time activity curve reached ninety percent of its peak value, was used as an index of GSA hepatic uptake, Ku and Kd, determined by two compartment analysis, were also used as indices. In rats of the fatty liver group, we confirmed microscopically that various degrees of fatty infiltration existed according to the diet period, and t 90 became significantly longer according to the severity of fatty infiltration. Ku and Kd also decreased according to the severity of fatty infiltration. In the rats with fatty infiltration and ischemia-reperfusion injury, t 90 also increased according to the severity of fatty infiltration, becoming longer than in the rats without ischemia-reperfusion injury. Quantitative analysis of GSA liver scintigraphy was useful for evaluating fatty liver and ischemia-reperfusion injury. (author)

Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

NARCIS (Netherlands)

Price, R.J.; Scott, M.P.; Walters, D.G.; Stierum, R.H.; Groten, J.P.; Meredith, C.; Lake, B.G.

2004-01-01

The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets

Evaluation of usefulness of 99mTc-GSA liver scintigraphy on fatty liver in the rat

International Nuclear Information System (INIS)

Kimoto, Mitsunori; Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo; Sakae, Katsuyoshi; Nagaya, Isao; Takeda, Yoshihiro; Hiraki, Yoshio

1994-01-01

99m Tc-GSA is a new liver-imaging radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes. We evaluated liver injury induced by fatty infiltration in the rats. Studies were performed in the Wistar rats under control conditions (6 cases), and with choline deficiency diet for 2, 4, 6, 10 and 12 weeks (6 cases respectively). 99m Tc-GSA was administered via the inferior vena cava. Immediately after injection, a dynamic imaging study was performed for 30 min. t 90 (the time at which the liver time-activity curve reached 90% of its peak), K u and K d (calculated by 2 compartment model) were used as parameters which reflect on asialoglycoprotein receptors on the hepatocytes. t 90 prolonged, and K u and K d decreased according to the severity of fatty infiltration. These results suggest that 99m Tc-GSA is useful for evaluating liver injury induced by fatty infiltration. (author)

Anti-inflammatory liposomes have no impact on liver regeneration in rats

DEFF Research Database (Denmark)

Jepsen, Betina Norman; Andersen, Kasper Jarlhelt; Knudsen, Anders Riegels

2015-01-01

Introduction: Surgical resection is the gold standard in treatment of hepatic malignancies, giving the patient the best chance to be cured. The liver has a unique capacity to regenerate. However, an inflammatory response occurs during resection, in part mediated by Kupffer cells, that influences...... the speed of regeneration. The aim of this study was to investigate the effect of a Kupffer cell targeted anti-inflammatory treatment on liver regeneration in rats. Methods: Two sets of animals, each including four groups of eight rats, were included. Paired groups from each set received treatment......-6. Conclusion: Low dose dexamethasone targeted to Kupffer cells does not affect histological liver cell regeneration after 70% hepatectomy in rats, but reduces the inflammatory response judged by circulating markers of inflammation. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of IJS...

Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.

Science.gov (United States)

Tahan, Veysel; Ozaras, Resat; Canbakan, Billur; Uzun, Hafize; Aydin, Seval; Yildirim, Beytullah; Aytekin, Huseyin; Ozbay, Gulsen; Mert, Ali; Senturk, Hakan

2004-09-01

Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

Effect of Withania Somnifera Root Powder on the Levels of Circulatory Lipid Peroxidation and Liver Marker Enzymes in Chronic Hyperammonemia

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B. Harikrishnan

2008-01-01

Full Text Available Withania somnifera (L Dunal (Solanaceae, commonly called Ashwagandha (Sanskrit is an Ayurvedic Indian medicinal plant, which has been widely used as a home remedy for several ailments. We have investigated the influence of W.somnifera root powder on the levels of circulatory ammonia, urea, lipid peroxidation products such as TBARS (thiobarbituric acid and reactive substances, HP (hydroperoxides and liver marker enzymes such as AST (aspartate transaminase, ALT (alanine transaminase and ALP (alkaline phosphatase, for its hepatoprotective effect in ammonium chloride induced hyperammonemia. Ammonium chloride treated rats showed a significant increase in the levels of circulatory ammonia, urea, AST, ALT, ALP, TBARS and HP. These changes were significantly decreased in rats treated with W.somnifera root powder and ammonium chloride. Our results indicate that W.somnifera offers hepatoprotection by influencing the levels of lipid peroxidation products and liver markers in experimental hyperammonemia and this could be due to (i the presence of alkaloids, withanolids and flavonoids, (ii normalizing the levels of urea and urea related compounds, (iii its free radical scavenging property and (iv its antioxidant property. The exact underlying mechanism is still unclear and further research needed.

Cypermethrin-induced histopathological, ultrastructural and biochemical changes in liver of albino rats: The protective role of propolis and curcumin

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Manal Abdul-Hamid

2017-06-01

Full Text Available Cypermethrin (CYP, an insecticide belongs to a synthetic pyrethroid, is used for agriculture and household applications. The present study aimed to examine the toxic effects of CYP on rat liver and to clarify the hepatoprotective effects of propolis (PRO and curcumin (CUR against CYP. This study was assessed in male albino rats, each weighting (120–150 g. The rats were equally divided into six groups as follow; the 1st control group, 2nd PRO group (100 mg/kg/day and 3rd CUR group (100 mg/kg/day. While 4th, 5th and 6th groups were orally treated with CYP (30 mg/kg/day, CYP plus PRO and CYP plus CUR, respectively for 28 days. The present study revealed that CYP-induced significant increase in hepatic markers enzymes (ALT, AST and ALP and elevation in MDA concomitant with significant decrease of SOD and GPx levels. Histological and histochemical results revealed extensive vacuolar degeneration of hepatocytes, fatty change, blood vessel congestion and fibrosis in the liver of CYP- treated group and depletion of glycogen, protein and DNA. Moreover, ultrastructural observations showed vacuolation, damage of mitochondria and nuclear changes. On the other hand, treatment with PRO and CUR led to an obvious improvement of the injured liver tissues and ameliorating the damaging effects of CYP. In conclusion, PRO is markedly effective than CUR in protecting rats against CYP-induced histopathological, ultrastructural and biochemical changes. This protection may be due to its antioxidant properties and scavenging abilities against active free radicals.

Presence of albumin mRNA precursors in nuclei of analbuminemic rat liver lacking cytoplasmic albumin mRNA.

OpenAIRE

Esumi, H; Takahashi, Y; Sekiya, T; Sato, S; Nagase, S; Sugimura, T

1982-01-01

Analbuminemic rats, which lack serum albumin, were previously found to have no albumin mRNA in the cytoplasm of the liver. In the present study, the existence of nuclear albumin mRNA precursors in the liver of analbuminemic rats was examined by RNA X cDNA hybridization kinetics. Albumin mRNA precursors were present in the nuclei of analbuminemic rat liver at almost normal levels, despite the absence of albumin mRNA from the cytoplasm. Nuclear RNA of analbuminemic rat liver was subjected to el...

Structure and function of the liver in conditions of chrome-isoniazid-rifampicin affection of rats after applying of sorbex

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N. I. Burmas

2014-09-01

Full Text Available The aim of this research was to assess the activity of marker enzymes of the liver and its biliary formation function in conditions of the affection of animals by hexavalent chromium compounds, isoniazid and rifampicin, after applying of sorbex. The experimental affection of rats of different age was carried in the conditions of combined injection of hexavalent chromium compounds (solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg during the 7th and 14th days, and sorbex enterosorbent was introduced in quantity of 150 mg/kg. The activity of marker enzymes of the liver was evaluated by the activity of alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP. The state of biliary formation function of the liver was evaluated by the content of total bilirubin (TB and bile acids (BA in blood. The most significant changes in ALT activity were observed in the liver of old animals by the combined effects of the abovementioned xenobiotics – the activity of ALT was decreased by the end of the experiment by 58% compared with the animals of intact control. Using of sorbex led to decreasing in blood serum and increasing in the liver of affected animals of the different age of ALT activity throughout the experiment. AST activity in blood serum increased, and it was the highest in old animals upon chrome-isoniazid-rifampicin affection on the 14th day of the research. With the use of sorbex, there was a tendency to normalization of this index in blood serum and liver of affected animals on the 7th day from the beginning of the experiment. It was found that the largest increase in ALP took place in blood serum of immature animals by the combined effects of toxicants. In the liver of affected animals the activity of ALP decreased throughout the experiment in all age groups of animals. Maximum corrective effect on the activity of ALP was shown by the enterosorbent in the liver of mature animals on

Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment.

Science.gov (United States)

Sil, Rajarshi; Chakraborti, Abhay Sankar

2016-09-01

Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome-induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Serum glucose and liver glycogen in gamma irradiated rats

International Nuclear Information System (INIS)

Ahlersova, E.; Ahlers, I.; Molcanova, A.

1988-01-01

Overnight fasted male rats of Wistar strain were irradiated with single whole-body doses of 4.78-7.17-9.57 and 14.35 Gy of gamma rays. After decapitation at intervals 1-28 d (4.78 and 7.17 Gy), 1-7 d (9.57 Gy) and 1-3 d (14.35 Gy) glucose concentration in serum and glycogen concentration in liver of irradiated and non-irradiated animals were determined. The higher was radiation dose the more expressive extent and depth of changes (hyperglycemia, accumulation of glycogen) occured. Blood glucose and liver glycogen may serve as a reliable and dose-dependent biological indicators of metabolic changes in irradiated rats. (author)

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver phosphoenolpyruvate carboxykinase (PEPCK) activity, glucose homeostasis and plasma amino acid concentrations in the most TCDD-susceptible and the most TCDD-resistant rat strains

Energy Technology Data Exchange (ETDEWEB)

Viluksela, M.; Pohjanvirta, R.; Tuomisto, J.T.; Tuomisto, J. (National Public Health Inst., Laboratory of Toxicology, Kuopio (Finland)); Unkila, M. (Department of Pharmacology and Toxicology, Univ. of Kuopio (Finland)); Stahl, B.U.; Rozman, K.K. (Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States) Section of Environmental Toxicology, GSF-Institut fuer Toxikologie, Neuherberg (Germany))

1999-08-01

Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of reduced gluconeogenesis by comparing dose-responses and time-courses of effects of TCDD on the activity of phosphoenolpyruvate carboxykinase (PEPCK) in liver, liver glycogen concentration as well as plasma concentrations of glucose and amino acids in both genders of TCDD-sensitive Long-Evans (L-E) rats and TCDD-resistant Han/Wistar (H/W) rats. A dose-dependent decrease in PEPCK activity was observed in H/W rats, but in L-E rats the activity was not decreased. However, TCDD impaired the strong increase in liver PEPCK activity observed in pair-fed controls of the L-E strain. Liver glycogen concentrations were severely decreased in L-E rats and moderately in H/W rats. This effect seems to be secondary to reduced feed intake, since a similar decrease was seen in pair-fed controls. Decreases in plasma glucose concentrations were also more profound in L-E rats than in H/W rats, but pair-fed controls were generally less affected. Circulating concentrations of amino acids were markedly increased in TCDD-treated L-E rats, which is likely to reflect increased mobilization of amino acids and their decreased metabolism in liver. Reduction of liver PEPCK activity cannot account for the sensitivity difference of these two strains of rats in terms of mortality. Nevertheless, the response of both strains of TCDD-treated rats regarding gluconeogenesis is different from that seen in pair-fed controls and suggesting that impairment of this pathway contributes to the development of the wasting syndrome. (orig.) With 7 figs., 2 tabs., 47 refs.

The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

Science.gov (United States)

Macan, Marija; Marija, Macan; Konjevoda, Paško; Paško, Konjevoda; Lovric, Jasna; Jasna, Lovrić; Koprivanac, Marijan; Marijan, Koprivanac; Kelava, Marta; Marta, Kelava; Vrkic, Nada; Nada, Vrkić; Bradamante, Vlasta; Vlasta, Bradamante

2011-06-01

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

International Nuclear Information System (INIS)

Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

2006-01-01

Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

Energy Technology Data Exchange (ETDEWEB)

Mei, Nan [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)]. E-mail: nan.mei@fda.hhs.gov; Arlt, Volker M. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Phillips, David H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Heflich, Robert H. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Chen, Tao [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)

2006-12-01

Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by {sup 32}P-postlabeling and mutant frequency (MF) was determined using the {lambda} Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N {sup 6}-yl]-aristolactam I, 7-[deoxyadenosin-N {sup 6}-yl]-aristolactam II and 7-[deoxyguanosin-N {sup 2}-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10{sup 8} nucleotides in liver and 95-4598 adducts/10{sup 8} nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10{sup -6} in liver compared with the MFs of 78-1319 x 10{sup -6} that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T {sup {yields}} T:A transversion was the predominant mutation in AA-treated rats; whereas G:C {sup {yields}} A:T transition was the main type of mutation in control

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

International Nuclear Information System (INIS)

Silva, R.N.; Bueno, P.G.; Avó, L.R.S.; Nonaka, K.O.; Selistre-Araújo, H.S.; Leal, A.M.O.

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

Energy Technology Data Exchange (ETDEWEB)

Silva, R.N. [Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Bueno, P.G. [Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Avó, L.R.S. [Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Nonaka, K.O.; Selistre-Araújo, H.S. [Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Leal, A.M.O. [Departamento de Medicina, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

2014-07-25

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.