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

Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effect of Ful on acetaminophen (AA)-induced hepatotoxicity in mice. Ful pretreatment (75-225 mg.kg-1, sc x 3 d) significantly decreased AA (500 mg.kg-1, ip)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Ful pretreatment (225 mg.kg-1, sc x 3 d) decreased hepatic cytochrome P-450, cytochrome b5, and NADPH-cytochrome c reductase by approximately 15-20%. Microsomes from Ful-pretreated mice, incubated in vitro with AA, produced less AA-glutathione. A 28% increase in urinary excretion of AA-glucuronide was observed in Ful (150 mg.kg-1, sc x 3 d) pretreated mice. Ful pretreatment had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronyltransferase activity towards AA. In summary, Ful pretreatment protects against AA-induced hepatotoxicity. One of the mechanisms for this protection appears to be the decreased AA toxic activation via P-450, as well as increased detoxication via glucuronidation of AA.
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PMID:Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity. 144

Overdosage of acetaminophen (AA) is known to produce acute liver toxicity in both humans and laboratory animals. Hamsters are especially sensitive to the hepatotoxic effect of AA. In the present study, hamsters pretreated with pregnenolone-16 alpha-carbonitrile (PCN; 75 mg/kg, ip, daily for 4 days) were given a single dose of AA (350-1200 mg/kg, ip) and liver function was determined 24 hr later. Serum activities of alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) as well as histopathology were used as indices of hepatotoxicity. PCN pretreatment decreased AA-induced mortality. PCN dramatically decreased ALT (93-97%) and SDH (63-98%) activities relative to control values from hamsters treated with AA alone, and remarkably decreased hepatic centrilobular necrosis produced by AA. To investigate the mechanism of this protective effect, the biliary and urinary excretion of AA metabolites were measured for 1 hr after administration of AA (150 mg/kg, iv) in bile-duct-cannulated hamsters. PCN pretreatment resulted in increased urinary and biliary excretion of AA-glucuronide and decreased biliary excretion of AA-glutathione. Microsomes from PCN-pretreated hamsters produced less benzoquinoneimine intermediate than controls, as determined by the formation of AA-glutathione. In addition, hepatic UDP-glucuronic acid and UDP-glucuronosyltransferase were significantly increased in PCN-pretreated hamsters. In conclusion, PCN pretreatment protected against AA-induced hepatotoxicity. The mechanism of this protection appears to be due to decreased formation of the reactive metabolite by the cytochrome P450 pathway, and an increased detoxication by enhanced glucuronidation of AA.
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PMID:Protective effect of pregnenolone-16 alpha-carbonitrile on acetaminophen-induced hepatotoxicity in hamsters. 206 28

The hepatoprotective effect of carsil (generic name silymarin) on a model of liver intoxication with D-galactosamine in rats is studied. The changes in the activity of the serum enzymes GOT, GPT, MDH, SDH, ICDH, AP. AhE and the total protein as well as the UDP-sugars content in the liver is investigated. Histochemical and electronmicroscopical investigations of the liver are carried out simultaneously. It is obvious that carsil prevents to a considerable degree the increase of the serum enzymes activity caused by a D-galactosamine injury, enhances the metabolic conversion of the UDP-hexosamine into UDP-acetylhexosamine in the liver and hastens the normalizing of the UDP-glucuronic acid content in the liver of rats. The biochemical and morphological changes under the influence of carsil and the possible biochemical mechanism of the drug action is discussed.
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PMID:Hepatoprotective effect of silymarin (carsil) on liver of D-galactosamine treated rats. Biochemical and morphological investigations. 723 Sep 79

Oleanolic acid (OA) is a triterpenoid compound that has been shown to protect against a number of hepatotoxicants, and is used in China to treat hepatitis. In the present study, we examined the effect of OA on acetaminophen (AA)-induced acute liver injury in mice and the mechanism(s) of protection. OA pretreatment (25-100 mg/kg s.c. for 3 days) remarkably decreased AA (500 mg/kg i.p.)-induced liver damage in mice, as indicated by decreased serum activities of alanine aminotransferase and sorbitol dehydrogenase, as well as by histopathological observation. Additionally, OA pretreatment mitigated AA (300-450 mg/kg i.v.)-induced depletion in liver glutathione (GSH) content. The protective effect was not evident until 24 hr after a single s.c. injection of OA (300 mg/kg) and lasted for 72 hr. To examine the mechanism of this protection, the biliary and urinary excretion of AA and AA metabolites were measured for 2 hr after AA administration (150 mg/kg i.v.) in bile duct-cannulated mice. OA pretreatment resulted in an increased urinary excretion of AA-glucuronide and a decreased biliary excretion of AA-GSH. Microsomes from OA-pretreated mice, incubated in vitro with AA, produced less benzoquinoneimine intermediate than controls, as determined by the formation of AA-GSH. Hepatic subcellular distribution of [3H] AA to the nuclear fraction was also decreased by OA. OA pretreatment of mice had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronosyltransferase activity toward AA. In summary, OA pretreatment dramatically protects against AA-induced hepatotoxicity in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice. 837 Nov 59

Ethinylestradiol (EE) induces intrahepatic cholestasis in experimental animals being its derivative, ethinylestradiol 17beta-glucuronide, a presumed mediator of this effect. To test whether glucuronidation is a relevant step in the pathogenesis of cholestasis induced by EE (5 mg/kg b.wt. s.c. for 5 consecutive days), the effect of simultaneous administration of galactosamine (200 mg/kg b.wt. i.p.) on biliary secretory function was studied. A single injection of this same dose of galactosamine was able to decrease hepatic UDP-glucuronic acid (UDP-GA) levels by 85% and excretion of EE-17beta-glucuronide after administration of a tracer dose of [3H]EE by 40%. Uridine (0.9 g/kg b.wt. i.p.) coadministration reverted the effect of galactosamine on hepatic UDP-GA levels and restored the excretion of [3H]EE-17beta-glucuronide. When administered for 5 days, galactosamine itself did not alter any of the serum markers of liver injury studied (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) or biliary secretory function. When coadministered with EE, galactosamine partially prevented the impairment induced by this estrogen in total bile flow, the bile-salt-independent fraction of bile flow, basal bile salt secretion, and the secretory rate maximum of tauroursodeoxycholate. Uridine coadministration partially prevented galactosamine from exerting its anticholestatic effects. In conclusion, galactosamine administration partially prevented EE-induced cholestasis by a mechanism involving decreased UDP-GA availability for subsequent formation of EE 17beta-glucuronide. The evidence thus supports the hypothesis that EE 17beta-glucuronide is involved in the pathogenesis of EE cholestasis.
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PMID:Galactosamine prevents ethinylestradiol-induced cholestasis. 1655 70