Effects of human placental extract on hepatic drug metabolizing enzyme.
Effects of acute or subchronic administration of human placental extract (HPE), a worldwide clinically used agent, on hepatic drug metabolizing enzyme activities were evaluated in rats. Hepatic microsomal cytochrome P-450 (Cyt. P450) and cytochrome b5 (Cyt. b5) contents and cytosolic glutathione S-transferase (GST) activities were maximally induced after various periods of time following a single intraperitoneal injection of HPE (4 ml/kg) whereas microsomal UDP-glucuronyltransferase (UDPGT) activities were inhibited significantly. All these altered effects were returned almost to the basal levels after 96 h of treatment. Subchronic treatment (30 days) with HPE (1,2 or 4 ml/kg) afforded a significant induction of Cyt. P-450 and Cyt. b5 levels and that of GST activities with a concurrent suppression of the activities of UDPGT and these results were found to be dose-dependent. However, microsomal NADPH cytochrome c reductase activity was not affected either by acute or subchronic treatment. The observed variations in the levels and activities of above house-keeping enzymes were discussed in relation to the possible carcinogenic risk of long-term treatment with this pharmaceutical agent.
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
A
A
Bishayee
K K
KK
Banerjee
M
M
Chatterjee
D000818:Animals; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014020:Tissue Extracts / Q000494:pharmacology*
D014020:Tissue Extracts; D006899:Mixed Function Oxygenases