Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The current study aims to assess contaminant levels and tissue burdens in hooded seal (Cystophora cristata) blubber, liver, and blood in association with cytochrome P450 (CYP) enzymes (CYP1A and -3A) and serum analytes (hepatic enzymes like alanine aminotransferase [ALT], aspartate aminotransferase, alkaline phosphatase [AP], and gamma-glutamyltransferase [GGT], serum proteins, and creatine kinase). Contaminant accumulation levels and patterns of polychlorinated biphenyls, chlorinated pesticides, and polybrominated diphenyl ethers (PBDEs) differed between tissues and seal groups, with the highest levels in liver. Pups showed higher liver contaminant levels, especially for PBDEs, than adults. These high levels might be associated with the ingestion of large amounts of contaminated milk and subsequent accumulation in the liver. Adult males and females mainly differed in PBDE levels, which were higher in females, possibly due to a sex-specific diet. The association between blubber contaminant burdens and the diagnostic enzymes ALT, GGT, and AP, and serum albumin, was inconclusive. In contrast, several CYP isoenzymes showed a clear positive relationship with the overall blubber contaminant burden, indicating enzyme induction following exposure to polyhalogenated hydrocarbons. Therefore, liver CYP isoenzymes may serve as a sensitive biomarker for long-term exposure to polyhalogenated hydrocarbons.
 ...
PMID:Tissue-specific contaminant accumulation and associated effects on hepatic serum analytes and cytochrome P450 enzyme activities in hooded seals (Cystophora cristata) from the Gulf of St. Lawrence. 1862 17

A molecular complex of simvastatin (SV) and glycyrrhyzic acid (GA) (at the ratio of 1 : 4), has been synthesized. The complex named "simvaglyzin" (SVG) was stable in aqeous and aqua-alcohol solutions at GA concentrations exceeding 0.2 mM. In vitro SVG acted as uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (Ki = 94 nM). Appearance of this inhibitory activity is associated with the cytochrome P450-dependent conversion of SVG. The addition of 1 mM methyrapone into incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by 39.15+/-8.27% and 38.85+/-3.04%, respectively. In vivo SVG showed dose-dependent cholesterol-lowering effect. In rats the cholesterol-lowering effect of SVG used at daily doses corresponding to 66 and 100 mg/kg of SV was equal to the effect of the daily dose 200 mg/kg of SV. The decreases of total cholesterol level in blood serum were 7%, 9% and 8%, respectively. Myotoxicity of those SVG doses estimated by creatine phosphokinase (CPK) activity in blood serum was lower than that of SV. In rats treated with SV the activity of CPK increased by 79% (p<0.01), while in SVG treated rats by 30% and 36% (p<0.05). Any increase of hepatotoxicity markers alanine aminotransferse or aspartate aminotransferase in blood serum was not observed. The data suggest pharmacological synergism attributed to the SV-GA complex formation and elevated safety of the resultant complex compared with the parent compound.
 ...
PMID:[Cholesterol lowering properties of a complex compound simvastatin with glycyrrhizic acid (simvaglyzin) in experimental models]. 1871 86

Renal ischemia/reperfusion (I/R) occurs in many clinical scenarios, including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the kidneys, culminating in local injury as well as distant organ dysfunction. The objectives of this study were to investigate the changes in the functions of the liver and the regulation of gene expression of cytochrome P450 (CYP) isozymes after renal I/R. Hepatoxocity was assessed by serum alanine aminotransferase (sALT), serum aspartate aminotransferase (sAST) and liver glutathione-S-transferase (GST) activities, liver glutathione (GSH) level, and histopathological examination. Hepatic cytochrome P4503A1 (CYP3A1) and cytochrome P4502E1 (CYP2E1) activities were measured by erythromycin N-demethylase (ERD) and aniline hydroxylase (ANH) activities, respectively. CYP3A1 and CYP2E1 mRNA expression was determined by RT-PCR. Results showed that activities of sALT and sAST were significantly increased, while hepatic CYP3A1and CYP2E1 activities as well as their respective mRNA levels were significantly decreased after renal I/R. Moreover, hepatic tissue congestion, degeneration, and local necrosis were observed in rats after 1, 4, and 8h renal reperfusion following 2h renal ischemia. In conclusion, the present study suggests that renal I/R can cause hepatotoxicity and gene expression down-regulation of CYP isozymes in rats.
 ...
PMID:Hepatotoxicity and gene expression down-regulation of CYP isozymes caused by renal ischemia/reperfusion in the rat. 1923 Jun 30

The present study was undertaken to examine the protective effects of an anthocyanin fraction (AF) obtained from purple-fleshed sweet potato on acetaminophen (paraceptamol [APAP])-induced hepatotoxicity in mice and to determine the mechanism involved. Mice pretreated with AF prior to APAP administration showed significantly lower increases in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic malondialdehyde formation than APAP-treated animals without AF. In addition, AF prevented hepatic glutathione (GSH) depletion by APAP, and hepatic GSH levels and GSH S-transferase activities were up-regulated by AF. APAP-induced hepatotoxicity was also prevented by AF, as indicated by liver histopathology findings. In addition, the effects of AF were examined on cytochrome P450 (CYP) 2E1, the major isozyme involved in APAP bioactivation. Treatment of mice with AF significantly and dose-dependently reduced CYP2E1-dependent aniline hydroxylation and CYP2E1 protein levels. Furthermore, AF had an antioxidant effect on FeCl(2)/ascorbate-induced lipid peroxidation in mouse liver homogenates and had superoxide radical scavenging activity. These results suggest that AF protects against APAP-induced hepatotoxicity by blocking CYP2E1-mediated APAP bioactivation, by up-regulating hepatic GSH levels, and by acting as a free radical scavenger.
 ...
PMID:Hepatoprotective effects of an anthocyanin fraction from purple-fleshed sweet potato against acetaminophen-induced liver damage in mice. 1945 32

The present study has determined the ability of dicofol, an organochlorine pesticide, to induce cytochrome P450 using rats treated with 1, 10, and 25mg/kg dicofol intraperitoneally for 4 days. Treatments with 10 and 25mg/kg dicofol produced dose-related increases of cytochrome P450 and cytochrome b(5) contents and NADPH-cytochrome c reductase, 7-ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aniline hydroxylase, and erythromycin N-demethylase activities in liver microsomes. The treatments also increased glutathione S-transferase and superoxide dismutase activities in liver cytosol. Dicofol at 1mg/kg produced a general trend towards increases of the aforementioned enzyme levels. The results of immunoblot analyses showed that 10 and 25mg/kg dicofol increased protein levels of CYP1A1, CYP2B, CYP2E1, and 3A in liver. RT-PCR data indicated that dicofol induced mRNA expression of liver CYP1A1, CYP2B, and CYP3A. Pretreatments of rats with 10 and 25mg/kg dicofol decreased phenobarbital-induced sleeping time by 34% and 39%, respectively. Dicofol pretreatment at 25mg/kg increased CCl4-induced serum alanine aminotransferase activity by 4.3-fold and aspartate aminotransferase activity by 4.1-fold. The present study demonstrates that dicofol has the ability to induce CYP1A1, CYP2B, CYP2E1, and CYP3A in the liver and increase phenobarbital metabolism and CCl4 toxicity in rats.
 ...
PMID:Induction of CYP1A1, 2B, 2E1 and 3A in rat liver by organochlorine pesticide dicofol. 1959 48

Oxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases.
 ...
PMID:Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice. 1965 5

The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg(-1) by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- alpha, NF-kappaB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.
 ...
PMID:The hepatotoxicity of multi-walled carbon nanotubes in mice. 1980 80

Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.
 ...
PMID:Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats. 1983 87

In this study, we examined the effect of Platycodi Radix (PR) supplementation in chronically alcoholic rats. Sprague-Dawley rats were divided into three groups: control group (no alcohol), alcohol group (36.8% of total calories), and 0.3% PR group. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased by alcohol treatment, and PR supplementation normalized the AST level. Moreover, alcohol-induced cytochrome P450 2E1 was decreased by PR treatment. Proteomic analysis of liver tissues of alcohol-exposed rats and PR-supplemented rats revealed that 50 different proteins functionally characterized as involved with cytoskeleton regulation, signal transduction, cytokine, apoptosis, and reactive oxygen species metabolism showed significant quantitative changes. The expression levels of glutathione S-transferase mu, Bcl-2-like protein, and peroxiredoxin IV were decreased in the alcoholic group, whereas the levels of these proteins were increased more than threefold in the PR group. However, the expression levels of smooth muscle actin, cytochrome P450 2D, mitogen-activated protein kinase 8, and 3alpha-hydroxysteroid dehydrogenase were increased in the alcohol group and were decreased in the PR group. These data suggest that the antioxidant enzymes may play a protective role against alcohol-induced damage via oxidative stress defense mechanisms induced by PR supplementation.
 ...
PMID:Proteomic analysis of the protective effects of Platycodi Radix in liver of chronically alcoholic rats. 2004 71


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