Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxidative metabolism of cocaine by the microsomal monooxygenase enzymes has been postulated to be essential for cocaine mediated hepatotoxicity (CMH). Endotoxin (lipopolysaccharide, LPS), a well-known cause of hepatic damage, previously has been demonstrated to dramatically increase CMH. The mechanism of this interaction has not been clearly elucidated, but cocaine oxidative metabolism appears to sensitize hepatocytes so that subsequent exposure to small amounts of LPS can further augment CMH. This study was conducted to investigate if dimethylaminoethyl-2,2-diphenylvalerate (SKF-525A) pretreatment inhibits LPS potentiation of CMH. For 5 consecutive days, male CF-1 mice were administered daily SKF-525A (50 mg/kg) or sterile saline followed an hour later by cocaine (20 mg/kg) or sterile saline. Four hours following the last cocaine or saline treatment, the mice were administered sterile saline 12x10(6) EU LPS/kg, i.p. The mice were sacrificed 18 h later by decapitation. Pretreatment with SKF-525A reversed the hepatic injury caused by cocaine alone or cocaine and LPS treatments, as indicated by both histologic evaluation and serum alanine transaminase (ALT) and aspartate transaminase (AST) activities. In particular, SKF-525A completely reversed the effects of cocaine alone on liver and blood reduced gluthathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) and hepatic glutathione reductase (GRx) activities. However, SKF-525A was ineffective against the effect of LPS alone on liver and blood GPx and CAT or on hepatic GSH and GRx, suggesting that these effects were not mediated by cytochrome P450 oxidative metabolism. The pattern of biochemical changes persisting with SKF-525A pretreatment in the LPS and cocaine group resembled those of the LPS alone group. The results suggest that cytochrome P450 oxidative metabolism of cocaine is largely responsible for CMH with potentiation by LPS achieved through a different mechanism involving oxidative stress.
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PMID:Inhibition of cocaine oxidative metabolism attenuates endotoxin potentiation of cocaine mediated hepatotoxicity. 1220 38

Cocaine produces hepatotoxicity by a mechanism that remains undefined but has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, and exposure to noninjurious doses of LPS increases the toxicity of certain hepatotoxins. Previously it was demonstrated that exposure to noninjurious doses of LPS dramatically increases cocaine-mediated hepatotoxicity (CMH). This study was conducted to investigate whether pretreatment with N-acetylcysteine (NAC), a glutathione (GSH) precursor and an antioxidant agent, inhibits LPS potentiation of CMH. For 5 consecutive days, male CF-1 mice were administered daily oral NAC (200 mg/kg) or sterile saline followed an hour later by cocaine (20 mg/kg) or sterile saline. Four hours following the last cocaine or saline treatment, the mice were administered 12 x 10(6) EU LPS/kg or sterile saline. For the cocaine alone and cocaine and LPS groups, NAC pretreatment significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities with absence of necrotic hepatic lesions, indicating a reduction of liver injury. In addition, in all groups pretreated with NAC, hepatic GSH concentration was significantly increased, as were hepatic and blood glutathione peroxidase (GPx) and catalase (CAT) activities. In conclusion, the results demonstrate that NAC pretreatment exerted a protective effect against LPS potentia-tion of CMH.
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PMID:N-acetylcysteine pretreatment decreases cocaine and endotoxin-induced hepatotoxicity. 1252 69

Benzanthrone (BA) and 3-bromobenzanthrone (3-BBA) are important dye intermediates used in the manufacture of various vat and disperse dyes. BA has been implicated as a cause of hepatic malfunctions and dermal lesions in workers. However, not much information on halogenated BAs, especially 3-BBA, is available. Experiments were designed to undertake a comparative safety assessment of both BA and 3-BBA, given orally at a dose of 50 mg/kg body weight for 10 days to guinea pigs. There was a significant decrease (25%) in body weight with 3-BBA, whereas BA treatment did not cause any change. Serum glutamate oxaloacetate transaminase and glutamate pyruvate transminase were found to be significantly (P<0.05) increased in 3-BBA- as well as in BA-treated animals. 3-BBA and BA led to substantial depletion of ascorbic acid in both liver and adrenal glands. However, depletion of ascorbic acid was more pronounced with 3-BBA (19.2-28.3%) than with BA (13.5-16.6%). 3-BBA and BA treatments caused 80% and 24% depletion of hepatic free sulfydryl content, while lipid peroxidation showed a significant enhancement of 73% and 47%, respectively. BA and 3-BBA caused decreases in cytochrome P-450 content and phase I enzymes particularly ethoxyresorufin- O-deethylase and aryl hydrocarbon hydroxylase, whereas phase II enzymes (quinone reductase and glutathione- S-transferase) were substantially increased. Activities of bio-antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase, were significantly increased by 153, 104, 20 and 67% in the 3-BBA-treated group, whereas the degree of increase in these parameters was relatively less in BA-treated group. The data indicate that both BA and 3-BBA can disturb membrane integrity by decreasing endogenous glutathione and ascorbic acid levels with a concomitant increase in lipid peroxidative damage. This may in turn lead to impairment of hepatic P-450-dependent monooxygenase, while the changes in antioxidant enzymes reveal oxidative stress. 3-BBA treatment caused dilation of portal triad with thickening of arterial wall, hyperplasia of Kupffer cells and influx of inflammatory cells between hepatic cords, which could be due to formation of Br(*) radical or due to formation of semiquinone type of intermediate following oxidation. The results may be interpreted to mean that industrial workers exposed to 3-BBA are at higher risk than those exposed to BA, and necessary precautions should be taken to safeguard their exposure risks.
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PMID:Comparative effect of benzanthrone and 3-bromobenzanthrone on hepatic xenobiotic metabolism and anti-oxidative defense system in guinea pigs. 1259 Mar 61

The protective effects and the possible mechanisms of dry matter of fermented filtrate (DMF) from Antrodia camphorata in submerged culture (ACSC) on H(2)O(2)-induced cytotoxicity in HepG2 and carbon tetrachloride (CCl(4))-induced hepatotoxicity in Sprague-Dawley rats were investigated. The results showed that the inhibitory effect of DMF and its crude triterpenoids on lipid peroxidation occurred in a dose-response manner in an AAPH/linoleic acid system. When HepG2 cells were pretreated with DMF at the concentration of 0.10 mg/mL for 4 h and then induced by 1 h of treatment with H(2)O(2) (100 microM), lipid peroxidation was significantly (p < 0.05) decreased, as measured by the formation of malondialdehyde. The oral pretreatment with DMF [0.25 and 0.50 mg/kg of body weight (bw)] for 5 consecutive days prior to the administration of a single dose of 40% CCl(4) (0.10 mL/100 g of bw, ip) significantly prevented the increase in serum levels of hepatic enzyme markers (alanine and aspartate aminotransferase) and liver lipid peroxidation (p < 0.05). Histopathological evaluation of the rat liver revealed that DMF reduced the incidence of liver lesions, including neutrophil infiltration, hydropic swelling, and necrosis induced by CCl(4) in rats. Moreover, reduced glutathione (GSH)-dependent enzymes (glutathione peroxidase, glutathione reductase, and glutathione S-transferase) and the GSH/GSSG ratio were significantly improved in the oral pretreatment DMF of rats (p < 0.01). The results suggest that DMF may play a role in preventing oxidative damage in living systems by up-regulating hepatic GSH-dependent enzymes to preserve the normal GSH/GSSH ratio and scavenging free radicals formed during CCl(4) metabolism.
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PMID:Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats. 1261 86

The effect of N-acetylcysteine (NAC) (Ig/kg body weight in saline for 7 days) against the damages induced by gamma ray was studied. Whole body exposure of rats to gamma-rays (3.5 Gy) caused increases in lipid peroxides (P < 0.01). Reduced glutathione (GSH) (P < 0.01) and total sulphydryl groups (TSH) (P < 0.05), were found to be increased probably to counteract the damages produced by the lipid peroxides. The plasma antioxidant vitamins E, C and A were reduced. The activities of antioxidant enzymes, superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were enhanced, which might be to eliminate the superoxide radical and H2O2 and accompanied by a fall in glutathione-s-transferase (GST) and glutathione reductase (GR) activity. The excessive production of free radicals and lipid peroxides might have caused the leakage of cytosolic enzymes such as aminotransferases (AST and ALT), lactate dehydrogenase (LDH), creatine kinase (CK) and phosphatases. Membrane damage is quite evident from histological studies undertaken in the intestinal tissue, which is susceptible to radiation damage. Intragastric pretreatment of NAC (1g/kg body weight in saline for 7 days) prevented the radiation induced damage to an appreciable extent. From the results it may be concluded that NAC is effective in protecting from the damages caused by gamma-ray radiations and its prospects as an adjuvant to radiotherapy should be considered.
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PMID:Protective effect of N-acetylcysteine against gamma ray induced damages in rats--biochemical evaluations. 1262 81

Piper betle L. is a commonly used masticatory in Asia. This study was carried out to investigate the hepatoprotective and antioxidant properties of P. betle, using ethanol intoxication as a model of hepatotoxic and oxidative damage. Ethanol-treated rats exhibited elevation of hepatic marker enzymes and disturbances in antioxidant defense when compared with normal rats. Oral administration of P. betle extract (100, 200, or 300 mg/kg body weight) for 30 days significantly (P <.05) decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), and lipid hydroperoxides in ethanol treated rats. The extract also improved the tissue antioxidant status by increasing the levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) and the activities of free radical-detoxifying enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in liver and kidney of ethanol-treated rats. The highest dose of P. betle extract (300 mg/kg body weight) was most effective. The results were comparable with the known hepatoprotective drug, silymarin. These results indicate that P. betle could afford a significant hepatoprotective and antioxidant effect.
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PMID:Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in ethanol-treated Wistar rats. 1263 94

Halothane, commonly used for anesthetizing humans and animals, is one of the most important volatile anesthetics and may cause the formation of free radicals during its biotransformation. Free radicals may lead to degeneration of liver cells. Vitamin E and glutathione peroxidase (GSH-Px) containing selenium are two natural antioxidants, and these may protect the cellular lipid and lipoproteins against oxidative damage caused by free radicals. Therefore, the purposes of the present study were to investigate the probable protective effects of intraperitoneally administered Se and vitamin E on liver enzymes and to determine some other hematological parameters in the halothane anesthesia of rats. All rats were randomly divided into five groups. The first group was used as a control, and physiological saline (0.9%) was intraperitoneally injected into these animals as a placebo. The second group was used as an anesthesia control group and was only anesthetized with halothane for two hours. The third group received intraperitoneally administered Se (Na2SeO3, 0.3 mg/200 g body weight), the fourth group vitamin E (dl-alpha-tocopheryl acetate, 100 mg/kg body weight), and the fifth group a Se plus vitamin E combination (Na2SeO3, 0.3 mg/200 g body weight + dl-alpha-tocopheryl acetate, 100 mg/kg body weight). The activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, triglycerides, erythrocyte counts, the packet-cell volume, hemoglobin concentrations and neutrophyle rates significantly increased (p < 0.05 to p < 0.01) after halothane anesthesia and returned to near control levels after Se, vitamin E and Se plus vitamin E injections. The values of cholesterol, total protein, white blood cell counts and lymphocyte rates significantly decreased (p < 0.05 to p < 0.01) in the anesthesia control group. However, the levels of albumin, total bilirubin, creatinine, the mean corpuscular volume, the mean corpuscular hemoglobin, and the mean corpuscular hemoglobin concentration were not statistically influenced. In conclusion, we have determined that halothane anesthesia affected some liver enzymes and some other biochemical and hematological parameters. Se, vitamin E and their combination may prevent the increase of liver enzymes after halothane anesthesia. Based upon these results, Se and vitamin E may play an important role in the indication of hepatic cellular injury produced by halothane.
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PMID:Effects of intraperitoneally injected selenium and vitamin E in rats anesthetized with halothane. 1275 99

Increased oxidative stress and impaired antioxidant defense mechanisms are important factors in the pathogenesis and progression of diabetes mellitus and other oxidant-related diseases. This study was designed to determine whether alpha-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (10 mg/kg ip) once daily for 14 days to normal and diabetic female Sprague-Dawley rats would prevent diabetes-induced changes in biomarkers of oxidative stress in liver, kidney and heart. Serum glucose concentrations, aspartate aminotransferase activity, and glycated hemoglobin levels, which were increased in diabetes, were not significantly altered by alpha-lipoic acid treatment. Normal rats treated with a high dose of alpha-lipoic acid (50 mg/kg) survived but diabetic rats on similar treatment died during the course of the experiment. The activity of glutathione peroxidase was increased in livers of normal rats treated with alpha-lipoic acid, but decreased in diabetic rats after alpha-lipoic acid treatment. Hepatic catalase activity was decreased in both normal and diabetic rats after alpha-lipoic acid treatment. Concentrations of reduced glutathione and glutathione disulfide in liver were increased after alpha-lipoic acid treatment of normal rats, but were not altered in diabetics. In kidney, glutathione peroxidase activity was elevated in diabetic rats, and in both normal and diabetic animals after alpha-lipoic acid treatment. Superoxide dismutase activity in heart was decreased in diabetic rats but normalized after treatment with alpha-lipoic acid; other cardiac enzyme activities were not influenced by either diabetes or antioxidant treatment. These results suggest that after 14 days of treatment with an appropriate pharmacological dose, alpha-lipoic acid may reduce oxidative stress in STZ-induced diabetic rats, perhaps by modulating the thiol status of the cells.
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PMID:Effects of alpha-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. 1283 33

The study investigates the effect of aqueous extract of fenugreek seeds (Trigonella foenum graecum) on lipid peroxidation and antioxidant status in experimental ethanol toxicity in rats. The ability of the seed extract to prevent iron-induced lipid peroxidation in vitro was also investigated. Ethanol feeding for 60 days resulted in significant increases in the activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase. The levels of serum lipid hydroperoxides and thiobarbituric acid reactive substances in liver and brain were also significantly elevated. Significantly lower activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase were observed in liver and brain accompanied by depletion in glutathione, ascorbic acid and alpha-tocopherol concentrations. Activity of Ca(2+) ATPase in brain was significantly lowered. Simultaneous administration of aqueous extract of fenugreek seeds with ethanol prevented the enzymatic leakage and the rise in lipid peroxidation and enhanced the antioxidant potential. The seeds exhibited appreciable antioxidant property in vitro which was comparable with that of reduced glutathione and alpha-tocopherol. Further, histopathological examination of liver and brain revealed that, aqueous extract of fenugreek seeds could offer a significant protection against ethanol toxicity.
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PMID:Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity. 1291 70

This study evaluated the effects of dehydroepiandrosterone (DHEA) on the oxidant [malondialdehyde (MDA)] and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH)] systems in liver after renal ischemia-reperfusion (IR) injury in rabbits. Thirty rabbits were randomly assigned to 3 groups of 10: group I (sham operation), group II (renal IR group), and group III (DHEA, 25 mg/kg, s.c., 15 min pre-ischemia). Renal IR injury in group II caused a decrease of SOD (25%), GPx (36%), and CAT (26%) activities and GSH levels (32%), and increases of MDA (30%) in liver and of ALT and AST activities in serum, compared to group I. DHEA administration decreased the hepatic MDA level (19%) and serum ALT activity (30%) (p <0.01 and p <0.05, respectively), and considerably increased hepatic GSH levels and GPx activities (p <0.01 for both) in group III, compared to group II. These results suggest that DHEA treatment has beneficial effects on antioxidant defenses against hepatic injury after renal IR in rabbits, possibly by augmenting GSH levels and lowering MDA production.
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PMID:Dehydroepiandrosterone improves hepatic antioxidant systems after renal ischemia-reperfusion injury in rabbits. 1458 61


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