Glutathione Levels In Rats Research Articles

Neuroprotective potential of carbamide forte on LPS‐induced experimental PD

AbstractBackgroundParkinson’s disease is a second most common age‐related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Increased oxidative stress and inflammation with decreased activity of glutathione peroxidase, superoxide dismutase (SOD), and catalase has been observed in PD patients. Carbamide Forte Brain and Memory Support is blend of 9 herbal brain‐enhancing ingredients to boost short term cognitive function and long‐term brain health and thus expected to be beneficial in cognition and movement disorder.MethodAdult male/female Sprague Dawley rats were ICV injected with LPS at a dose of 0.2 mg/kg body weight into substantia nigra pars compacta with the help of stereotaxic apparatus. Carbamide Forte was administered per orally at 80 and 160 mg/kg body weight, 4 days after to LPS infusion.ResultInfusion of single ICV‐LPS produced significantly decreased in body weight, locomotor activity, motor coordination, antioxidant defense enzymes and significantly increased oxidative stress markers in the striatum. Chronic administration of carbamide forte (for 21days) significantly attenuated LPS induced movement disabilities in Narrow beam walk, Horizontal ladder beam walk test, OFT and also significantly reduce the oxidative‐nitrosative stress and antioxidants enzymesas evidence by decrease in malondialdehyde and nitrite levels and restored the reduced glutathione level in rats & neuroprotective potential of CF with morphological changes seen in our histological assessment. The observed result of the present study is indicative of the therapeutic potential of Carbamide Forte in PD.ConclusionIt could be concluded that the observed neuroprotective effect of Carbamide Forte may be due to antioxidant and neuroprotective potential.

The Effect of Dietary Supplement on Glutathione Level in Rats

Background: Oxidative stress occurs due to decreased glutathione inside the body. Some supplements may promote and stimulate glutathione production in the liver. This article aims to investigate the impact of different supplements on enhancing glutathione synthesis in rats’ livers. For this purpose 42 rats (male albino) were separated into 7 groups, each including 6 animals with average weights ranging between 150 and 160 g. Group 1 (control) and different groups consumed a basal diet for 8 weeks, whereas group 2 received 500 mg/kg bw of L-cysteine daily. Group 3 received 250 mg/kg bw of methionine, while group 4 got 250 mg/kg of L cysteine plus 125 mg/kg of methionine daily. Spirulina (20 mg/kg bw), turmeric (500 mg/kg bw), and dried garlic (500 mg/kg bw), respectively, were given to groups 5, 6, and 7.
 Results: Utilizing the various dietary supplements decreased levels of liver function enzymes, bilirubin, urea, creatinine, and malondialdehyde while enhancing levels antioxidant enzymes of liver, and increased glutathione of kidneys and liver. However, cysteine alone at 500 mg/kg bw decreased glutathione formation in the liver and kidneys. Compared to the amino acid supplements (group 2, 3, 4) used, spirulina, turmeric, and dried garlic had a significant impact on reducing liver function enzymes, bilirubin, uric acid, creatinine, urea, and malondialdehyde and increasing antioxidant enzymes, and glutathione while turmeric supplement showed the best influence. Using dietary supplements did not result in any pathological modifications in the liver tissues, but there were some unsatisfactory minor alterations. However, group 2 showed considerable pathological developments in the liver tissues.
 Conclusion: According to the findings, using the suggested dietary supplement except for cysteine alone can promote and encourage glutathione synthesis in different organs, especially the liver, hence alleviating the effects of oxidative stress associated with several illnesses.

The Antipsychotic Effects of Omega-3 Fatty Acids in Rats

In humans, omega-3 fatty acids are necessary for cell membranes, brain function and nerve transmission continuation. When animals are exposed to a new environment-or as a result of an apomorphine application that creates an agonistic effect on D1 and D2 receptors-they display behavioral reactions like rearing and stereotypy. This study aims to reveal the possible antipsychotic and oxidative effects of omega-3 fatty acids by comparing with chlorpromazine, a conventional antipsychotic drug, through evaluating the novelty-induced rearing and apomorphine-induced stereotypic behaviors, as well as malondialdehyde and glutathione levels in rats. Twenty-eight, adult, male, Wistar rats were used in the study. Briefly, 4 groups of rats (n = 7) were administered docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg intraperitoneally [IP]), DHA + EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg IP), chlorpromazine (1 mg/kg, IP) and isotonic saline (1 mL/kg, IP). One hour later, apomorphine (2 mg/kg, subcutaneously) was administered to each rat. After the apomorphine administration, rats were observed for stereotypic behavior. This study shows that omega-3 fatty acids, "similar to antipsychotics," reversed the psychotic like effects, increase of oxidants and decrease of antioxidants that are composed experimentally in rats. The application of omega-3 fatty acids has antipsychotic effects and causes an oxidative imbalance. This study adds new evidence to the current literature regarding the possible antipsychotic effects of omega-3 fatty acids.

Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH, and NO in a rat model of pentylenetetrazole-induced epileptic seizure

Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen and nitrogen species. The objective of this study was to investigate the effects of Neuropeptide Y on oxidative and nitrosative balance and brain-derived neurotrophic factor levels induced by pentylenetetrazole (a standard convulsant drug) in the hippocampus of Wistar rats. Three groups of seven rats were treated intraperitoneally as follows: group 1 (saline + saline) 1 ml saline, group 2 (salin + Pentylenetetrazole) 1 ml saline 30 min before Pentylenetetrazole; and group 3 (Neuropeptide Y + Pentylenetetrazole) 60 μg/kg Neuropeptide Y 30 min before 60 mg/kg Pentylenetetrazole. After 24 h, the animals were euthanized by decapitation. Hippocampus were isolated to evaluate the malondialdehyde, glutathione, nitric oxide, and brain-derived neurotrophic factor levels in three rat groups. The results of this study demonstrated that while intraperitoneally administered neuropeptide Y did not result in a statistically significant difference in BDNF levels, its administration caused a statistically significant decrease in malondialdehyde and nitric oxide levels and an increase in glutathione levels in rats with pentylenetetrazole-induced epileptic seizure. Neuropeptide Y were able to reduce nitroxidative damage induced by pentylenetetrazole in the hippocampus of Wistar rats.

High Performance Liquid Chromatography Coupled with Pre-column Derivatization for Determination of Oxidized Glutathione Level in Rats Exposed to Paraquat.

Glutathione (GSH) is one of the most important antioxidants that plays an essential role in detoxification of reactive oxygen species (ROS) which oxidizes to glutathione disulfide (GSSG). Paraquat (PQ), awidely used herbicide, causes pulmonary injury with the productionof ROS. Excessive ROS accumulation as a consequence of PQ exposure are frequently targeted by GSH thereby oxidative stress leads to depletion of cellular GSH by transforming of GSH to glutathione disulfide (GSSG). A precise method of measuring of GSSG concentration in plasma as indicator of oxidative stress is needed. Some analytical techniques such as high-performance liquid chromatography (HPLC), gas chromatography and capillary electrophoresis have been used for determination of GSSG concentration. In the present study, a new HPLC method with fluorescence detection based on derivatization of the amine group of glutathione with 9-fluorenylmethyl chloroformate (FMOC-Cl) was developed. Male Wistar albino rats exposed to different doses of PQ (20-60 mg/kg) and control group were used and after protein precipitation, their plasma was subjected to derivatization with FMOC in the presence of borate buffer. The derivatized samples were injected to HPLC system with C18 column, mobile phase consisting of methanol and phosphate buffer, λem= 315 nm, λex= 260 nm. Among all experimental groups, the rats which received 60 mg/kg PQ, showed a significant increase in the amount of oxidized glutathione (GSSG) compared to the control group. In this study, the applied derivatization and HPLC method made it possible to measure small amounts of glutathione in plasma using a precise and sensitive technique.

Effects of glycyrrhizin on biliary transport and hepatic levels of glutathione in rats

The purpose of the current study was to determine whether glycyrrhizin (GL) maintains hepatic glutathione (GSH) levels by inhibiting GSH biliary secretion in normal rats. The effects of glycyrrhizin on hepatic glutathione content, bile flow and biliary secretion of glutathione were examined. Because glutathione is a substrate for multidrug resistance associated protein-2 (Mrp2/ABCC2), the inhibitory effects of GL on Mrp2 in isolated perfused rat liver and in Mrp2-expressing Sf9 membrane vesicles were also examined using the Mrp2 substrate methotrexate (MTX) and estradiol-17-β-glucuronide (E2 17G). The hepatic content of glutathione in rats following GL perfusion (43.7 µmol/l) in isolated liver perfusion and GL intravenous treatment (25 mg/kg) was significantly higher than that for the control. A marked and dose-dependent decrease in the excretion of glutathione was observed. In addition, the secretion rate of MTX was decreased by 57% in isolated liver perfusion in GL-treated rats. Moreover the ATP-dependent uptake of E2 17G by Mrp2 membrane vesicles was decreased by 75.9% in the 20 µm GL group and by 60.5% in the 2 µm GL group. In conclusion, glycyrrhizin increases hepatic glutathione content possibly through inhibition of Mrp2 which then reduces the biliary excretion of glutathione.

Inhibition of betaine-homocysteine S-methyltransferase in rats causes hyperhomocysteinemia and reduces liver cystathionine β-synthase activity and methylation capacity

Methylation of homocysteine (Hcy) by betaine-Hcy S-methyltransferase (BHMT) produces methionine, which is required for S-adenosylmethionine (SAM) synthesis. We have recently shown that short-term dietary intake of S-(Δ-carboxybutyl)-dl-Hcy (D,L-CBHcy), a potent and specific inhibitor of BHMT, significantly decreases liver BHMT activity and SAM concentrations but does not have an adverse affect on liver histopathology, plasma markers of liver damage, or DNA methylation in rats. The present study was designed to investigate the hypothesis that BHMT is required to maintain normal liver and plasma amino acid and glutathione profiles, and liver SAM and lipid accumulation. Rats were fed an adequate (4.5 g/kg methionine and 3.7 g/kg cystine), cysteine-devoid (4.5 g/kg methionine and 0 g/kg cystine), or methionine-deficient (1.5 g/kg methionine and 3.7 g/kg cystine) diet either with or without L-CBHcy for 3 or 14 days. All rats fed L-CBHcy had increased total plasma Hcy (2- to 5-fold) and reduced liver BHMT activity (>90%) and SAM concentrations (>40%). S-(Δ-carboxybutyl)-l-Hcy treatment slightly reduced liver glutathione levels in rats fed the adequate or cysteine-devoid diet for 14 days. Rats fed the methionine-deficient diet with L-CBHcy developed fatty liver. Liver cystathionine β-synthase activity was reduced in all L-CBHcy-treated animals, and the effect was exacerbated as time on the L-CBHcy diet increased. Our data indicate that BHMT activity is required to maintain adequate levels of liver SAM and low levels of total plasma Hcy and might be critical for liver glutathione and triglyceride homeostasis under some dietary conditions.

Effects of Taurine on Glutathione Peroxidase, Glutathione Reductase and Reduced Glutathione Levels in Rats

The aim of the present study is to investigate the effects of oral administration of taurine on endogenous glutathione peroxidase (GPx) and Glutathione Reductase (GR) activities and reduced glutathione (GSH) level in normal rats. Normal saline (Group I) or 5% taurine in normal saline was administered in dose of 50 mg (Group II), 250 mg (Group III) or 500 mg kg(-1) of body weight (Group IV) through intragastric intubation for 60 days. GPx and GR enzyme activities and GSH and taurine levels were determined in liver, heart, stomach, kidney and plasma of normal Wistar rats. GPx activity showed an increase in liver, heart, stomach and plasma. GR activity increased in kidney and decreased in liver and plasma. GSH levels increased in liver, stomach and decreased in kidney. Liver showed an increase and heart, stomach and kidney a decrease in taurine level in taurine administered rats when compared to control rats. The results varied from organ to organ and the observed variations among organs might be related to their respective enzymatic, non-enzymatic antioxidant potential and its functions. From the present study it may be concluded that long term oral administration of taurine affects GPx, GR and GSH levels in normal rats.

The Effects of Sildenafil Citrate on Ischemic Colonic Anastomotic Healing in Rats: Its Relationship Between Nitric Oxide and Oxidative Stress

The purpose of this study was to examine the effects of sildenafil citrate on normal and ischemic colon anastomosis in the rat model by measuring the levels of blood and colonic tissues nitric oxide, thiobarbituric acid reactive substrates (as a marker of lipid peroxidation), and glutathione (as an antioxidant). Normal (group 1 and 3) and ischemic anastomosis (group 2 and 4) were performed in four equal rat groups (n = 14). Orally 10 mg/kg per day of sildenafil citrate therapy were applied in group 3 and group 4 after operation. Seven rats of the each group were killed on postoperative days 3 and 7. Sildenafil citrate therapy was resulted in elevated nitric oxide levels in both normal and ischemic anastomotic tissues (p < 0.0001 and p < 0.03) at postoperative day 3. Tissue thiobarbituric acid reactive substrate levels were elevated in rats with normal anastomosis by sildenafil therapy (p < 0.001) at postoperative days 3 and 7 (p < 0.05). Sildenafil therapy given to the normal anastomosis group has significantly higher tissue nitric oxide levels than the normal anastomosis group without therapy at postoperative day 7 (p < 0.001). On postoperative day 7, plasma nitric oxide levels were decreased by sildenafil citrate in rats with normal (p < 0.01) and ischemic anastomosis (p < 0.05). The beneficial effect of sildenafil citrate also was seen for erythrocyte glutathione levels in rats with normal anastomosis at postoperative day 7 and in rats with ischemic anastomosis at postoperative day 3. Our results suggest that sildenafil citrate may affect ischemic anastomotic healing due to its possible effects on nitric oxide metabolism and lipid peroxidation. However, functional implication of this agent further needs to be elucidated.

Depletion of Liver Glutathione Levels in Rats: A Potential Confound of Nose-Only Inhalation

Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

Subchronic intoxication with chlorfenvinphos, an organophosphate insecticide, affects rat brain antioxidative enzymes and glutathione level

Organophosphate pesticides (OP) belong to the class of xenobiotics that are intentionally released to the environment. Toxicity of these compounds is mainly due to inhibition of acetylcholinesterase (AChE), but many authors postulate that OP in acute as well as in chronic intoxication disturb the redox processes, changing the activities of antioxidative enzymes and causing enhancement of lipid peroxidation in many organs. Epidemiological studies have demonstrated a relationship of certain human diseases with pesticide exposure and with changes in antioxidative enzymes. There is also evidence that oxidative stress is an important pathomechanism of neurological disorders such as Alzheimer disease and Parkinson disease, cardiovascular disorders and many others. The study objective was to investigate the activities of brain antioxidative enzymes and reduced glutathione level in rats subchronically intoxicated with chlorfenvinphos. In the rat brain the activities of such enzymes as superoxide dismutase, catalase, glutathione peroxidase and reductase were found to increase, while reduced glutathione level decreased in chlorfenvinphos intoxication. Based on experimental findings of this study, it can be suggested that subchronic administration of chlorfenvinphos leads to a change in the brain oxidative status and that the change occurs at a dose of 0.3 mg/kg/day, i.e., twice smaller than LOAEL level for rats.

Effects of carbamazepine on hepatic glutathione level in rats and determination of carbamazepine and its epoxide metabolite in plasma by HPLC.

We investigated whether carbamazepine, which is known to be metabolized to an electrophilic epoxide derivative in the body, causes any decrease, analogous to the action of epoxides, of hepatic glutathione (GSH) level in rats. Carbamazepine was administered to rats and liver GSH levels were determined spectrophotometrically. Neither a single low nor repeated low doses (30 mg/kg) of carbamazepine (CBZ) produced a statistically significant difference in GSH levels relative to controls. A single high dose of CBZ (100 mg/kg) produced a large and significant decrease relative to control (GSH level 3.82 +/- 0.64 vs 6.54 +/- 0.45 mumol GSH/g liver). CBZ and its metabolite carbamazepine-10,11-epoxide were determined in plasma by HPLC after the high dose of carbamazepine administration. The concentrations of carbamazepine and carbamazepine-10,11-epoxide were 18.9 +/- 2.9 micrograms/ml and 10.7 +/- 2.8 micrograms/ml, respectively.

Effects of N-acetylcysteine on lung glutathione levels in rats after burn injury

This study was designed to determine the effect of N-acetylcysteine (NAC, a natural hydroxyl radical scavenger) treatment on levels of pulmonary malondialdehyde (MDA, the end product of lipid peroxidation) and glutathione (GSH, a natural antioxidant) in thermally injured rats. Severe skin scald injury (30 percent TBSA) caused a significant decrease in GSH levels, and a significant increase in MDA levels in lung tissue both at 1 h and 1 day postburn injury.Treatment of rats with NAC (15 mg/kg intraperitoneally, 15 min and 12 h following the burn) significantly improved GSH levels, and decreased ongoing lipid peroxidation at 1 day.This study showed that thermal injury resulted in increased pulmonary lipid peroxidation, and this remote organ injury was decreased by treatment with NAC. In addition NAC, a scavenger of hydroxyl radicals, improved GSH levels in the lungs. The higher level of GSH in the lungs of the burned rats treated with NAC could be due to either a decrease in the rate of degradation of GSH or to an increase in its synthesis. No data about these possibilities are provided.

Effect of glutamine supplemented TPN on tissue glutathione levels in rats with bacterial peritonitis

Effect of glutamine supplemented TPN on tissue glutathione levels in rats with bacterial peritonitis

Inhibition of glutathione synthesis in the liver leads to S -adenosyl-L-methionine synthetase reduction

The hepatic levels of glutathione in rats treated with buthionine sulfoximine (4 mmol/kg), an inhibitor of glutathione synthesis, were 72.5% +/- 4.9% of those determined in control animals. This decrease in glutathione concentration was prevented by the administration of glutathione monoethyl ester (7.5 mmol/kg). S-Adenosyl-L-methionine-synthetase activity in the liver of rats treated with buthionine sulfoximine was 39.4% +/- 6.5% of that determined in control animals. Again, glutathione monoethyl ester prevented the effect of buthionine sulfoximine on S-adenosyl-L-methionine-synthetase activity. There was a close correlation (r = 0.936) between the hepatic levels of glutathione and S-adenosyl-L-methionine-synthetase activity. The hepatic concentration of S-adenosyl-L-methionine in buthionine sulfoximine-treated animals was 59.7% +/- 3.7% of that measured in control rats. Contrasting with the protective effects mentioned above, glutathione monoester had no preventive action on buthionine sulfoximine-induced S-adenosyl-L-methionine depletion. Electron microscopic examination of liver samples of rats after buthionine sulfoximine administration showed evidence of liver degeneration, which was attenuated by glutathione monoethyl ester treatment. Glutathione (7.5 mmol/kg) treatment was less effective than glutathione monoethyl ester in attenuating buthionine sulfoximine effects on hepatic S-adenosyl-L-methionine metabolism and morphology. The reduction of S-adenosyl-L-methionine-synthetase activity observed after treatment with buthionine sulfoximine and its prevention by glutathione monoethyl ester, as well as the correlation between the activity of this enzyme and glutathione levels, indicate that glutathione plays an important role in maintaining S-adenosyl-L-methionine-synthetase activity in the liver.

Recovery of normal glutathione levels in rats

Recovery of normal glutathione levels in rats

Enhancement of Pancreatic and Hepatic Glutathione Levels in Rats during Cyanohydroxybutene Intoxication

Enhancement of Pancreatic and Hepatic Glutathione Levels in Rats during Cyanohydroxybutene Intoxication

Enhancement of pancreatic and hepatic glutathione levels in rats during cyanohydroxybutene intoxication

1-Cyano-2-hydroxy-3-butene (CHB), a cruciferous plant product, is hepatotoxic, pancreatotoxic, and elevates glutathione (GSH) in liver and pancreas. Whether GSH elevation is preceded by a depletion related to toxic insult, or whether toxicity and GSH elevation are unrelated, is not known. To evaluate the temporal relationship between toxicity and GSH levels, male Fisher 344 rats (6/group) were given CHB (200 mg/kg po) and killed up to 96 hr after dosing. At death, histological and ultrastructural evaluations and GSH GSSG determinations were performed on liver and pancreas. In pancreas, dilatation of the cisternae of the rough endoplasmic reticulum (RER) was evident from 2 hr, becoming progressively more severe 4 and 6 hr after CHB. Frank apoptosis and loss of zymogen granules was evident by 6 hr, becoming widespread by 12 hr. Recovery had commenced by 72 hr, and 50% of treated rats had normal pancreata by 96 hr. No hepatic lesions were observed at this dose. Pancreatic GSH was depressed below 20% at 2 and 4 hr, rose to a maximum of 540% by 12 hr, and remained elevated in treated rats throughout the study (275% at 96 hr). Hepatic GSH only fell to 50%, rose to 150–180%, and returned to normal by 96 hr. While this pattern of depletion and rebound following exposure to hepatotoxins is common, the exaggerated and persistent elevation of pancreatic GSH is unprecedented.

Effect of oral glutathione on hepatic glutathione levels in rats and mice.

Administration of oral glutathione (GSH) increases hepatic GSH levels in fasted rats, in mice treated with GSH depletors such as diethyl maleate and in mice treated with high doses of paracetamol. An increase in hepatic GSH levels after administration of oral GSH does not occur in animals treated with buthionine sulphoximine, an inhibitor of GSH synthesis. Administration of oral GSH leads to an increase in the concentration of L-cysteine, a precursor of GSH, in portal blood plasma. Oral administration of L-methionine produced a significant decrease of hepatic ATP in fasted rats, but not in fed rats. Administration of N-acetylcysteine or GSH did not affect the hepatic ATP levels. The results show that the oral intake of GSH is a safe and efficient form of administration of its constituent amino acids in cases when GSH synthesis is required to replete hepatic GSH levels.

Modulation of blood glutathione levels in rats with gastric ulcer hci-induced

Modulation of blood glutathione levels in rats with gastric ulcer hci-induced