Protective effect of N2-mercaptopropionylglycine on rats and dogs liver during ischemia/reperfusion process Efeito protetor do N2-mercaptopropionilglicina em ratos e cães submetidos a isquemia/reperfusão normotécnica do fígado
Emilio Elias Abdo
Full Text Available BACKGROUND: N2-mercaptopropionylglycine is a powerful super oxide synthesis inhibitor and has been tested as a preventive agent of metabolic and structural hepatic damage in the ischemia/reperfusion process. AIM: To analyze some effects of N2-mercaptopropionylglycine administration to animals of two species submitted to normothermic liver ischemia/reperfusion. MATERIAL AND METHODS: Twenty-two rats and 22 dogs were divided into four groups: group I: rats that received intravenous saline 0.9%; group II: rats that received 100 mg/kg of N2-mercaptopropionylglycine; group III: dogs that received saline intravenous 0.9% and group IV: dogs that received 100 mg/kg N2-mercaptopropionylglycine. RESULTS: Ten minutes after the saline or drug administration, each group was submitted to left lobe liver ischemia for 25 minutes followed by reperfusion. Biochemical studies 24 hours after reperfusion revealed a significantly lower elevation of transaminases in animals of groups II (AST = 271 ± 182; ALT = 261 ± 161 and IV (AST = 101 ± 45; ALT = 123 ± 89 when compared to the controls group: I (AST = 2144 ± 966; ALT = 1869 ± 1040 00 and III (AST = 182 ± 76.51; ALT = 277 ± 219, respectively. Histology study demonstrated a significantly minor aggression to animals of groups II and IV when compared to groups I and III, respectively. CONCLUSION: These results suggest a significant release of free radicals of oxygen in the process and that N2-mercaptopropionylglycine may have a significant protective effect on liver parenchyma when submitted to ischemia/reperfusion.RACIONAL: O medicamento N2-mercaptopropionilglicina é um potente inibidor da síntese de radicais superóxidos e foi testado como agente preventivo de lesão metabólica e estrutural do parênquima hepático, no processo de isquemia/reperfusão. OBJETIVOS: Analisar alguns efeitos da administração do N2-mercaptopropionilglicina a animais de duas espécies submetidas a isquemia/reperfusão normot
Kumar, S.; Devi, P.U. (Rajasthan Univ., Jaipur (India). Radiation Biology Lab.)
The protective effect of MPG on the peripheral blood leukocytes of Swiss albino mice was studied after a single whole-body exposure to 10 Gy of /sup 60/Co radiation with or without prior injection of MPG. The results indicated that the drug was not effective in modifying the radiation-induced changes in the total leukocyte, lymphocyte and neutrophil counts, whereas a significant drop in the number of degenerating cells was observed at the early postirradiation intervals in the drug-treated animals, indicating a protection against the direct cell killing effect of radiation.
Ghose, A.; Pant, R.D. (Institute of Nuclear Medicine and Allied Sciences, Delhi (India))
2-Mercaptopropionyl glycine (MPG) treatment has not improved leucocytopenia in laboratory mice after 760R or 1060R gamma exposure inspite of the fact that reduction in the total leucocyte count was slightly less in MPG treated group on the 10th day after 760R gamma exposure; leucocytopenia was more marked in MPG treated group on the 14th day and 21st day after 760R gamma exposure as compared to that in control animals. Two hundred mg/kg of 2-aminoethyl isothiuronium bromide hydrobromide (AET) treatment which is half the recommended dose for radioprotection has offered considerable protection to leucopenia after 760R and 1060R gamma exposure. It has also helped substantially in rapid recovery of lymphocytes after 760R exposure. MPG combined with two hundred mg/kg AET has not offered any extra radioprotection to peripheral blood leucocytes after 760R gamma exposure, on the contrary the combination has been less effective than the respective AET dose given singly. Similar result has been noted with combination treatment of MPG and 40 mg/kg AET in 1060R gamma exposure.
Bhagat, R.M.; Kumar, A. (Himachal Pradesh Univ., Simla (India). Dept. of Bio-sciences)
Modifying effects of MPG (2-Mercaptopropionylglycine) have been studied on bone marrow granuloid cells of Swiss albino mice after injecting radiocalcium (/sup 45/Ca) at the dose of 37 kBq/g body weight MPG was injected 30 minutes before radiocalcium injection at dose 20 mg/kg body weight intraperitoneally and also MPG was injected at various repeated doses. Present observations indicate that MPG in repeated doses is effective in reducing radiation injury in bone marrow granuloid cells of Swiss albino mice following radiocalcium (/sup 45/Ca) internal irradiation.
Bhagat, R.M.; Kumar, A. (Himachal Pradesh Univ., Simla (India). Dept. of Bio-sciences)
Adult male Swiss albino mice were given 20 mg/kg body weight of MGP (2-mercaptopropionylglycine) intraperitoneally 15-30 minutes before /sup 45/Ca injection at dose 37 kBq/g body weight. MPG was also administered at various repeated doses. Radioprotective effects of MPG were studied on total erythroid cells (pronormoblasts and normoblasts) at various autopsy intervals (1, 3, 7, 14 and 28 days) posttreatment. It has been observed that MPG in repeated doses is effective in reducing the radiation-induced changes in the erythroid cells of bone marrow in Swiss albino mice following /sup 45/Ca internal irradiation.
Capillary electrophoresis coupled with inductively coupled mass spectrometry as an alternative to cloud point extraction based methods for rapid quantification of silver ions and surface coated silver nanoparticles.
Qu, Haiou; Mudalige, Thilak K; Linder, Sean W
Speciation and accurate quantification of ionic silver and metallic silver nanoparticles are critical to investigate silver toxicity and to determine the shelf-life of products that contain nano silver under various storage conditions. We developed a rapid method for quantification of silver ions and silver nanoparticles using capillary electrophoresis (CE) interfaced with inductively-coupled plasma mass spectrometry (ICPMS). The addition of 2-mercaptopropionylglycine (tiopronin) to the background electrolyte was used to facilitate the chromatographic separation of ionic silver and maintain the oxidation state of silver. The obtained limits of detection were 0.05 μg kg(-1) of silver nanoparticles and 0.03 μg kg(-1) of ionic silver. Nanoparticles of varied sizes (10-110 nm) with different surface coating, including citrate acid, lipoic acid, polyvinylpyrrolidone and bovine serum albumin (BSA) were successfully analyzed. Particularly good recoveries (>93%) were obtained for both ionic silver and silver nanoparticle in the presence of excess amount of BSA. The method was further tested with six commercially available dietary supplements which varied in concentration and matrix components. The summed values of silver ions and silver nanoparticles correlated well with the total silver concentration determined by ICPMS after acid digestion. This method can serve as an alternative to cloud point extraction technique when the extraction efficiency for protein coated nanoparticles is low.
Full Text Available A simple spectrophotometric method for the determination of N-acetyl-L-cysteine (NAC and N-(2-mercaptopropionylglycine (MPG in pharmaceutical preparations was developed, validated, and used. The proposed equilibrium method is based on a coupled two-step redox and complexation reaction. In the first step, Fe(III is reduced to Fe(II by NAC or MPG. Subsequently, Fe(II is complexed with 2,4,6-tripyridyl-s-triazine (TPTZ. Several analytical parameters of the method were optimized for NAC and MPG analysis in the concentration range from 1.0 μM to 100.0 μM. Regression analysis of the calibration data showed a good correlation coefficient (0.9999. The detection limit of the method was 0.14 μM for NAC and 0.13 μM for MPG. The method was successfully applied to quantify NAC and MPG in pharmaceutical preparations. No interferences were observed from common pharmaceutical excipients.
Dukoff, David James; Hogg, David William; Hawrysh, Peter John; Buck, Leslie Thomas
Oxygen deprivation triggers excitotoxic cell death in mammal neurons through excessive calcium loading via over-activation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This does not occur in the western painted turtle, which overwinters for months without oxygen. Neurological damage is avoided through anoxia-mediated decreases in NMDA and AMPA receptor currents that are dependent upon a modest rise in intracellular Ca(2+) concentrations ([Ca(2+)]i) originating from mitochondria. Anoxia also blocks mitochondrial reactive oxygen species (ROS) generation, which is another potential signaling mechanism to regulate glutamate receptors. To assess the effects of decreased intracellular [ROS] on NMDA and AMPA receptor currents, we scavenged ROS with N-2-mercaptopropionylglycine (MPG) or N-acetylcysteine (NAC). Unlike anoxia, ROS scavengers increased NMDA receptor whole-cell currents by 100%, while hydrogen peroxide decreased currents. AMPA receptor currents and [Ca(2+)]i concentrations were unaffected by ROS manipulation. Because decreases in [ROS] increased NMDA receptor currents, we next asked whether mitochondrial Ca(2+) release prevents receptor potentiation during anoxia. Normoxic activation of mitochondrial ATP-sensitive potassium (mKATP) channels with diazoxide decreased NMDA receptor currents and was unaffected by subsequent ROS scavenging. Diazoxide application following ROS scavenging did not rescue scavenger-mediated increases in NMDA receptor currents. Fluorescent measurement of [Ca(2+)]i and ROS levels demonstrated that [Ca(2+)]i increases before ROS decreases. We conclude that decreases in ROS concentration are not linked to anoxia-mediated decreases in NMDA/AMPA receptor currents but are rather associated with an increase in NMDA receptor currents that is prevented during anoxia by mitochondrial Ca(2+) release.
Palomeque, Julieta; Rueda, Omar Velez; Sapia, Luciana; Valverde, Carlos A; Salas, Margarita; Petroff, Martin Vila; Mattiazzi, Alicia
Angiotensin (Ang) II-induced apoptosis was reported to be mediated by different signaling molecules. Whether these molecules are either interconnected in a single pathway or constitute different and alternative cascades by which Ang II exerts its apoptotic action, is not known. To investigate in cultured myocytes from adult cat and rat, 2 species in which Ang II has opposite inotropic effects, the signaling cascade involved in Ang II-induced apoptosis. Ang II (1 micromol/L) reduced cat/rat myocytes viability by approximately 40%, in part, because of apoptosis (TUNEL/caspase-3 activity). In both species, apoptosis was associated with reactive oxygen species (ROS) production, Ca(2+)/calmodulin-dependent protein kinase (CaMK)II, and p38 mitogen-activated protein kinase (p38MAPK) activation and was prevented by the ROS scavenger MPG (2-mercaptopropionylglycine) or the NADPH oxidase inhibitor DPI (diphenyleneiodonium) by CaMKII inhibitors (KN-93 and AIP [autocamtide 2-related inhibitory peptide]) or in transgenic mice expressing a CaMKII inhibitory peptide and by the p38MAPK inhibitor, SB202190. Furthermore, p38MAPK overexpression exacerbated Ang II-induced cell mortality. Moreover, although KN-93 did not affect Ang II-induced ROS production, it prevented p38MAPK activation. Results further show that CaMKII can be activated by Ang II or H(2)O(2), even in the presence of the Ca(2+) chelator BAPTA-AM, in myocytes and in EGTA-Ca(2+)-free solutions in the presence of the calmodulin inhibitor W-7 in in vitro experiments. (1) The Ang II-induced apoptotic cascade converges in both species, in a common pathway mediated by ROS-dependent CaMKII activation which results in p38MAPK activation and apoptosis. (2) In the presence of Ang II or ROS, CaMKII may be activated at subdiastolic Ca(2+) concentrations, suggesting a new mechanism by which ROS reset the Ca(2+) dependence of CaMKII to extremely low Ca(2+) levels.
Zhi Ye; Qulian Guo; E Wang; Yundan Pan; Qing Li; Honghao Zhou
BACKGROUND: Brief exposure to the anesthetic sevoflurane results in delayed neuroprotection.However, few studies have addressed delayed neuroprotection after preconditioning with a single administration of sevoflurane.OBJECTIVE: To explore the relationship between a single preconditioning administration of sevoflurane and reactive oxygen species production and protein kinase C-epsilon (PKC- ε ) translocation.DESIGN, TIME, AND SETTING: The randomized, controlled, animal experiment was conducted at the Central Laboratory, Xiangya Hospital, Central South University, China from November 2007 to April 2008.MATERIALS: A total of 120 healthy, male, Sprague Dawley rats were equally and randomly assigned into five groups: sham operation, ischemia/reperfusion, sevoflurane, 2-mercaptopropionylglycine (2-MPG, a selective reactive oxygen species scavenger) + sevoflurane (MPG + sevoflurane), and MPG. Sevoflurane (Baxter, USA) and MPG (Sigma, USA) were used in this study.METHODS: Intervention consisted of three procedures. (1) MPG injection: a selective reactive oxygen species scavenger, MPG (20 mg/kg), was infused into the rat caudal vein in the MPG and MPG + sevoflurane groups. (2) Sevoflurane preconditioning: 30 minutes following MPG injection,rats in the sevoflurane and MPG + sevoflurane groups breathed a mixed gas of 2.4% sevoflurane and 97.6% oxygen for 60 minutes. Rats in the sham operation, ischemia/reperfusion, and MPG groups breathed 100% pure oxygen for 60 minutes. (3) Ischemia/reperfusion: 24 hours after sevoflurane or pure oxygen preconditioning, middle cerebral artery occlusion models were established in the ischemia/reperfusion, sevoflurane, MPG + sevoflurane, and MPG groups.Following 2 hours ischemia/6 hours and 24 hours reperfusion, the carotid artery was separated, but the middle cerebral artery was not occluded, in the sham operation group.MAIN OUTCOME MEASURES: In the ischemic hemisphere, PKC-ε translocation in the rat parietal cortex was measured by Western