Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare the hepatoprotective effects of 10 oleanane-type triterpenoid compounds on three known hepatotoxicants in mice. These compounds include oleanolic acid, ursolic acid, uvaol, alpha-hederin (alpha-H), hederagenin, glycyrrhizin, 18 alpha-glycyrrhetinic acid (alpha-GA), 18 beta-glycyrrhetinic acid (beta-GA), 19 alpha-hydroxyl asiatic acid 28-O-beta-D-glucoside (HAG), and 19 alpha-hydroxyl asiatic acid (HA). They were administrated sc for 3 days at 200 mumol/kg, except for alpha-H, which was given at 100 mumol/kg for 2 days. Acute liver injury was produced in male CF-1 mice by CCl4 (15 microliters/kg, ip), acetaminophen (500 mg/kg, ip), and cadmium chloride (3.7 mg/kg, iv). Liver damage was assessed by serum activities of alanine aminotransferase and sorbitol dehydrogenase, as well as by histopathological examination. alpha-Hederin, ursolic acid, and oleanolic acid markedly decreased the toxicity produced by all three hepatotoxicants. Uvaol significantly decreased CCl4- and Cd-induced hepatotoxicity, but had no effect on acetaminophen toxicity. Glycyrrhizin, alpha-GA, and beta-GA decreased acetaminophen-induced liver injury, whereas hederagenin, HAG, and HA did not protect against any of the hepatotoxicants. In addition, alpha-hederin, ursolic acid, oleanolic acid, and uvaol increased hepatic metallothionein levels by 87-, 48-, 28-, and 10-fold, respectively, as determined by the Cd/hemoglobin assay. In conclusion, among the 10 triterpenoid compounds examined, alpha-hederin, ursolic acid, and oleanolic acid appear to be the most effective in protecting against CCl4-, acetaminophen-, and Cd-induced liver injury.
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PMID:The effects of 10 triterpenoid compounds on experimental liver injury in mice. 812 11

alpha-Hederin (alpha-Hed) is a triterpenoid saponin that has been shown to protect against some hepatotoxicants. This study examined the protective effect of alpha-Hed against cadmium (Cd) hepatotoxicity and the mechanism of protection. alpha-Hed pretreatment (100 mumol/kg, sc) dramatically decreased Cd (3.7 mg/kg, iv) hepatotoxicity as indicated by a reduction of serum alanine aminotransferase and sorbitol dehydrogenase, as well as by histopathological examination. alpha-Hed did not produce protection by decreasing the distribution of Cd to the liver, as higher amounts of Cd were found in the liver of alpha-Hed-pretreated mice. However, there was a marked alteration in subcellular distribution of Cd in the alpha-Hed-pretreated mice, with much less Cd distributing to nuclei, mitochondria, and microsomes and more in the cytosol. The increased cytosolic Cd was found primarily bound to a low-molecular-weight protein, metallothionein (MT). alpha-Hed (10-300 mumol/kg, sc) produced a dose-dependent increase in hepatic MT with a 100-fold increase over controls 24 hr after a single injection of 100 mumol/kg, as determined by the Cd/hemoglobin assay. The hepatic MT increase produced by alpha-Hed is relatively long lasting, in that it is still eight times control values 6 days after a single administration. The induction of MT was also relatively specific for the liver, as little or no increase in MT was observed in other tissues. Furthermore, alpha-Hed increased both hepatic MT-I and MT-II levels. Northern blot analysis revealed that alpha-Hed rapidly increased MT mRNA levels. In conclusion, alpha-Hed decreases the hepatotoxicity of Cd by inducing MT, which binds Cd in the cytosol, and thus reduces the amount of Cd in the critical cellular organelles. alpha-Hed is an effective inducer of both MT-I and MT-II in liver, and this effect is associated with an increase in MT mRNA.
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PMID:Induction of metallothionein by alpha-hederin. 833 95

The protective effects of alpha-Hederin on carbon tetrachloride-induced hepatotoxicities were investigated in mice. Pretreatment with alpha-Hederin prior to the administration of carbon tetrachloride significantly prevented the increase in serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activity and lipid peroxidation in a dose dependent manner. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by pretreatment with alpha-Hederin alone but pretreatment with alpha-Hederin protects carbon tetrachloride-induced depletion of hepatic glutathione levels. The effects of alpha-Hederin on the cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were investigated. alpha-Hederin markedly decreased the P450 2E1-specific activities of p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. These results demonstrate that treatment of mice with alpha-Hederin decreases the expression and activities of P450 2E1 enzyme, and reduces biotransformation of carbon tetrachloride, and diminished carbon tetrachloride-induced liver injury.
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PMID:The prevention of carbon tetrachloride-induced hepatotoxicity in mice by alpha-hederin: inhibiton of cytochrome P450 2E1 expression. 963 40