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)

The effects of p-phenylbenzoic acid (PPBA) on sulfation and glucuronidation was studied in rats. Following intravenous injection of 14C-p-tert-butylphenol (14C-TB, 50 micromol/kg) with PPBA (50 micromol/kg), the sulfation of 14C-TB was decreased by 38.8% and its glucuronidation increased by 62.3%. In a system of isolated hepatocytes, the sulfation of 14C-TB increased and its glucuronidation decreased following the addition of 100 microM of PPBA, suggesting competitive inhibition by the glucuronidation of PPBA. On the other hand, the sulfation of 14C-TB decreased and its glucuronidation increased following the addition of 400 microM of PPBA, which represents the plasma concentration of PPBA in vivo. At this concentration, significant leakage of GOT, GPT and LDH into the medium was observed, whereas, no significant change in the ATP synthesis was noted. Microsomes preincubated with 60 microM of PPBA, which represents the intracellular concentration of PPBA in the liver in vivo, showed no change in the level of glucuronidation of 14C-TB. These results suggest that PPBA in the plasma injures cell membranes and causes a leakage of cytosolic sulfotransferase, whereas UDPGT, embedded in the microsomal membrane, does not leak from the injured cell membrane, resulting in the decrease in sulfation and increase in glucuronidation. Similar in vivo effects on the sulfation/glucuronidation ratio were observed for benzoic acids substituted with benzoyl and phenoxy groups.
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PMID:Study on effects of p-phenylbenzoic acid on change of sulfation and glucuronidation in rats. 1203 18

The hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D-galactosamine (GalNH(2)). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin-layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH(2) (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH(2)-only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH(2)-induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal gamma-glutamyl transferase (gamma-GT) by 42% and 46%, respectively. Administration of kolaviron to GalNH(2)-intoxicated mice also restored glucose-6-phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the liver of GalNH(2)-intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione-S-transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH(2)-induced toxicity was essentially prevented as indicated by a liver histopathologic study of liver slices from mice pretreated with kolaviron, fraction I and fraction II. This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH(2)-induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.
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PMID:Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seeds. 1644 85