Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatoprotective effects of momordin Ic and oleanolic acid obtained from Kochiae Fructus (KF), the fruit of a traditional Oriental medicinal plant, were evaluated against carbon tetrachloride (CCl4)-induced liver damage in rats. Male Sprague-Dawley rats were divided into four groups: control, CCl4-treated, CCl4 plus momordin Ic-treated (MMDIc-CCl4), and CCl4 plus oleanolic acid-treated (OAA-CCl4). Momordin Ic (30 mg/kg of body weight) and oleanolic acid (30 mg/kg of body weight) were orally administered once a day for 14 days. A mixture of 0.2 mL/100 g of body weight of CCl4 in olive oil (1:1, vol/vol) was injected 30 minutes after the final administration of momordin Ic and oleanolic acid. The momordin Ic and oleanolic acid pretreatments resulted in significantly lower serum transaminase, lactic dehydrogenase, and gamma-glutamyltransferase levels in the CCl4-treated rats. The CCl4-treated rats had significantly lower activities of glutathione, glutathione reductase, glutathione S-transferase, superoxide dismutase, catalase, and glutathione peroxidase. However, pretreatment with momordin Ic and oleanolic acid reduced the effect of CCl4 and helped maintain levels of the enzymes. Pretreatment with momordin Ic and oleanolic acid resulted in significantly lower production of aminopyrine N-demethylase and aniline hydroxylase in the CCl4-treated rats. Pretreatment with momordin Ic resulted in lower catalase and aminopyrine N-demethylase activity induction by CCl4, towards normalization. Momordin Ic and oleanolic acid obtained from KF appear to contribute to alleviating the adverse effects of CCl4 treatment by enhancing the hepatic antioxidant defense system.
 ...
PMID:Momordin Ic and oleanolic acid from Kochiae Fructus reduce carbon tetrachloride-induced hepatotoxicity in rats. 1611 9

The hepatoprotective effects of rubiadin, a major constituent isolated from Rubia cordifolia Linn., were evaluated against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Rubiadin at a dose of 50, 100 and 200 mg/kg was administered orally once daily for 14 days. The substantially elevated serum enzymatic activities of serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and gamma-glutamyltransferase (gamma-GT) due to carbon tetrachloride treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were also restored towards normalization. In addition, rubiadin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4 intoxicated rats in a dose dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post treatment against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that rubiadin has a potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats.
 ...
PMID:Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn. 1621 20

The protective effects of water extract of Du-Zhong (Eucommia ulmoides Oliv.) leaves (WEDZ) and its active compound (protocatechuic acid; PCA) on liver damage were evaluated by carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Wistar rats were orally treated with WEDZ (0.1, 0.5, and 1.0 g/kg bw) or PCA (0.1 g/kg bw) with administration of CCl4 (0.5 ml/rat, 20% CCl4 in olive oil) for 28 consecutive days. It showed that CCl4-treated rats increased the relative organ weights of liver and kidney. CCl4-induced rats liver damage and significantly (p<0.05) increased the GOT, GPT, LDH and ALP levels in serum as compared with the control group. Treatment with WEDZ or PCA could decrease the GOT, GPT, LDH and ALP levels in serum when compared with CCl4-treated group. CCl4-treated rats also significantly (p<0.05) decreased the GSH content in liver and trolox equivalent antioxidant capacity (TEAC) in serum whereas increased (p<0.05) MDA content in liver as compared with the control group. Treatment with WEDZ or PCA also significantly (p<0.05) increased the GSH content and significantly (p<0.05) decreased the MDA content in liver. Administration of WEDZ or PCA could increase the activities of GPx, GRd and GST in liver. Liver histopathology showed that WEDZ or PCA reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasmic vacuolization, hepatic necrosis and fibrous connective tissue proliferated induced by CCl4 in rats. The data suggest that oral administration with WEDZ for 28 consecutive days significantly decrease the intensity of hepatic damage induced by CCl4 in rats.
 ...
PMID:Du-Zhong (Eucommia ulmoides Oliv.) leaves inhibits CCl4-induced hepatic damage in rats. 1670 2

1. Liver fibrosis is the compensatory state of cirrhosis. In the long asymptomatic period, it is imperative to select a proper dosing regimen for drugs that are applicable to hepatic fibrosis. Otherwise, progressive deterioration to uncompensated cirrhosis may occur. The present study explored the characteristics of drug metabolism in fibrotic liver. 2. A rat precision-cut fibrotic liver slice (PCFLS) technique was established and the metabolism of verapamil was studied employing this technique. A rat hepatic fibrosis model was successfully induced integrating complex factors that included a high-fat diet, alcohol and CCl4. The PCFLS were incubated under different conditions and lactate dehydrogenase leakage, glutathione S-transferase activity and 3[4,5-dimethythiazole-2-yl]-2,5-diphenyltetrazolium bromide reduction were used as indices to assess PCFLS viability. Activities of phase I and phase II metabolizing enzymes were monitored following treatment with cytochrome P450 (CYP) inducers. Normal and fibrotic liver slices were incubated individually with 10 micromol/L verapamil. The concentration of verapamil in the medium was determined by high-performance liquid chromatography and intrinsic clearance (Cl(int)) was calculated on the basis of the concentration-time curve. 3. The results showed that the PCFLS viability remained steady throughout the 6 h of culture when the thickness of slices was 300 microm and pH of the medium was 7.0; CYP inducers (phenobarbital and ethanol) enhanced CYP2E1, CYP3A1/2 and uridine diphosphate-glucuronate transferase (UDPGT) activities, respectively, in a time-dependent manner. The Cl(int) (microL/min per mg) values differed significantly between normal (9.7 +/- 1.8) and fibrotic (5.6 +/- 1.4) liver slices (P < 0.01). 4. These results suggested that the PCFLS could remain viable for 2-6 h under appropriate conditions. The stability and inducibility of drug-metabolizing enzymes of PCFLS were also demonstrated. Furthermore, the metabolic rate of verapamil in PCFLS was decreased. These findings add further support to the use of PCFLS as a tool to study drug metabolism and to guide clinical medication.
 ...
PMID:Establishment of rat precision-cut fibrotic liver slice technique and its application in verapamil metabolism. 1743 8

Subchronic toxicity of carbon tetrachloride (CCl4) was examined by inhalation exposure of F344 rats and BDF1 mice of both sexes to 0, 10, 30, 90, 270 or 810 ppm (v/v) CCl4 vapor for 13 wk (6 h/d and 5 d/wk). In the high exposure levels at 270 and 810 ppm, altered cell foci in the livers of both rats and mice, and fibrosis and cirrhosis in the rat liver were observed. Hematoxylin and eosin-stained altered cell foci of rats were recognized as glutathione-S-transferase placental form (GST-P) positive foci, which are preneoplastic lesions of hepatocarcinogenesis. The most sensitive endpoint of CCl4-induced toxicity was fatty change with large droplets in rats of both sexes and male mice, and cytoplasmic globules in male mice, as well as increased relative liver weight in male rats. Those endpoints were manifested at 10 ppm and the LOAEL was determined as 10 ppm for the hepatic endpoints in rats and mice. Enhanced cytolytic release of liver transaminases into plasma in rats and mice and its close association with hepatic collapse in mice were observed at medium and high levels of inhalation exposure. Both CCl4-induced hematotoxicity and nephrotoxicity were observed in both rats and mice, but those toxicities were manifested at higher exposure concentrations than hepatotoxicity. The LOAEL for the hepatic endpoint and the GST-P-stained altered cell foci provide relevant animal data for reconsidering the occupational exposure limit val1ue of 5 ppm for CCl4 and strengthen the evidence of CCl4-induced hepatocarcinogenicity which is used in its carcinogenicity classification.
 ...
PMID:Thirteen-week inhalation toxicity of carbon tetrachloride in rats and mice. 1769 May 17

Puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicine for thousands of years. The purpose of this study was to investigate the protective effects of puerarin against hepatotoxicity induced by carbon tetrachloride (CCl4) and the mechanism of its hepatoprotective effect. In mice, pretreatment with puerarin prior to the administration of CCl4 significantly prevented the increased serum enzymatic activity of alanine aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. In addition, pretreatment with puerarin significantly prevented both the depletion of reduced glutathione (GSH) content and the decrease in glutathione S-transferase (GST) activity in the liver of CCl4-intoxicated mice. Hepatic GSH levels and GST activity were increased by treatment with puerarin alone. CCl4-induced hepatotoxicity was also prevented, as indicated by liver histopathology. The effects of puerarin on cytochrome P450 (CYP) 2E1, the major isozyme involved in CCl4 bioactivation, were also investigated. Treatment of the mice with puerarin resulted in a significant decrease in the CYP2E1-dependent aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the CYP2E1 protein levels were also lowered. Puerarin exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. These results suggest that the protective effects of puerarin against the CCl4-induced hepatotoxicity possibly involve mechanisms related to its ability to block CYP-mediated CCl4 bioactivation, induction of GST activity and free radical scavenging effects.
 ...
PMID:Protective effects of puerarin on carbon tetrachloride-induced hepatotoxicity. 1803 10

Solanum nigrum L. (SN) is an herbal plant that has been used as hepatoprotective and anti-inflammation agent in Chinese medicine. In this study, the protective effects of water extract of SN (SNE) against liver damage were evaluated in carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Sprague-Dawley (SD) rats were orally fed with SNE (0.2, 0.5, and 1.0 g kg(-1) bw) along with administration of CCl4 (20% CCl4/corn oil; 0.5 mL kg(-1) bw) for 6 weeks. The results showed that the treatment of SNE significantly lowered the CCl4-induced serum levels of hepatic enzyme markers (GOT, GPT, ALP, and total bilirubin), superoxide and hydroxyl radical. The hepatic content of GSH, and activities and expressions of SOD, GST Al, and GST Mu that were reduced by CCl4 were brought back to control levels by the supplement of SNE. Liver histopathology showed that SNE reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by CCl4 in rats. Therefore, the results of this study suggest that SNE could protect liver against the CCl4-induced oxidative damage in rats, and this hepatoprotective effect might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects.
 ...
PMID:Hepatoprotective effects of Solanum nigrum Linn extract against CCl(4)-induced oxidative damage in rats. 1804 81

Peroxidation products formed from polyunsaturated lipids have DNA damaging potential. 4-oxo-2-hexenal (4-OHE), generated by the oxidation of omega-3 fatty acids, has been demonstrated to be mutagenic in vitro as assessed in the Ames test. To examine the carcinogenic risk of 4-OHE in vivo, initiation activity was investigated in a five-week liver assay, established to be effective for screening of carcinogenic potential of mutagens. Seven-week-old male F344 rats underwent two-thirds partial hepatectomy (PH) and were administered 4-OHE intragastrically at doses of 128, 80, 64, 40, 32, 20, or 0 mg/kg body weight (b.w.) at 18 hours thereafter, then being fed on diet containing 0.015% 2-acetylaminofluorene from weeks 2 to 4. All rats were given with 0.8 ml/kg b.w. CCl4 at week 3. At week 5, all survivors were sacrificed and initiation activity was assessed with reference to induction of glutathione S-transferase placental form (GST-P) positive foci in the liver. Mortality was significantly increased to 72.7% in the 128 mg/kg b.w. dose group compared with 0.9% in the control group. However, the average number of GST-P positive foci in the "128" dose group was 3.26-/+1.66 foci/cm2, not significantly different from the control value (2.78?1.33). Areas of GST-P positive foci were also similar (1.11-/+0.5 and 1.53-/+1.33 mm2/cm2 in "128" and the control groups, respectively). These results showed 4-OHE to have no significant initiation activity in.
 ...
PMID:Lack of initiation activity of 4-oxo-2-hexenal, a peroxidation product generated from omega-3 polyunsaturated fatty acids, in an in vivo five-week liver assay. 1815 70

The potential of carbon tetrachloride (CCl4) to induce pre-neoplastic lesions in rat liver using a medium-term liver assay (Ito method) for the prediction of carcinogenicity was examined by nose-only inhalation exposure of male rats (15/group) to CCl4 vapor at concentrations of 0, 1, 5, 25, 125 ppm for 6h/day, 6 day/week, for a period of 6 weeks. The numbers and area of glutathione S-transferase placental (GST-P) positive foci were then determined. Additionally, other histopathological observations on the livers were recorded and serum chemical parameters and CCl4 concentrations in blood were measured. The areas and numbers of GST-P positive foci significantly increased in the CCl4-exposed rats at 25 and 125 ppm; but not at concentrations of 1 and 5 ppm. CCl4 blood concentration 24h after initiation of exposure in the 125 ppm group remained at about 5% of the 6h maximum concentration. These data from CCl4-exposed rats clearly show that inhalation exposure can be used in the rat medium-term liver assay, the method is available for the screening of volatile chemicals and is therefore a useful tool in cancer risk assessment. This is the first report of the use of inhalation exposure in this medium-term predictive assay.
 ...
PMID:The inhalation exposure of carbon tetrachloride promote rat liver carcinogenesis in a medium-term liver bioassay. 1822 44

Bee's wax produced by honeybees is rich in polyphenols. As the polyphenols are thought to protect cell constituents against oxidative damage through scavenging of free radicals, the present work was undertaken to evaluate the effects of polyphenols extracted from bees wax on the oxidative stress induced by carbon tetrachloride (CCl4) in rats. The polyphenols extracted by 80% methanol from bee wax (PBW) were fed to Wistar rats at 100 mg/kg body weight and 200 mg/kg body weight for 14 days in order to study its antioxidative and antihepatotoxic effects against CCl4 (1.5 ml/kg body weight)-induced stress. On 15th day all the rats were sacrificed, blood was collected for serum and organs/tissues were excised for biochemical analysis. The results showed a significant decrease in hepatic antioxidant enzyme activities viz. catalase, glucose-6-phosphate dehydrogenase (G-6-PDH), glutathione peroxidase (GSH-Px), glutathione reductase, superoxide dismutase (SOD) and a significant increase in glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (GGT) by CCl4, probably due to the peroxidative effects. The prophylactic use of PBW at 200 mg/kg level resulted in a significant increase in CCl4-induced reduction in catalase, G-6-PDH, GSSGR and SOD. The hepatic levels of lipid peroxides viz. malondialdehyde, conjugated dienes and lipid hydroperoxides, enhanced by the administration of CCl4 were brought down by the ingestion of PBW at a level of 200 mg/kg. The hepatotoxicity caused by the administration of CCl4 was reduced significantly. Hence, it is concluded that the polyphenols from bees wax exhibit hepatoprotective and antioxidative properties in
 ...
PMID:Bees wax polyphenols as suppressor of CC1--induced oxidative stress in rats. 1847 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>