Effect of glycerol-induced acute renal failure and di-2-ethylhexyl phthalate on the enzymes involved in biotransformation of xenobiotixs.
The effects of di-(2-ethylhexyl)-phthalate (DEPH) on the levels of cytochrome P-450 and b5 monooxygenases were studied in the rat kidney and liver in acute renal failure induced by glycerol. Intramuscular injection of glycerol (50%,10 ml x kg(-1)) to rats produced proximal tubular damage and acute renal failure. The indicators of renal function, serum urea and creatinine significantly increased (480 and 350 percent, respectively). In control and glycerol-treated animals DEPH had no significant effect on the concentrations of serum urea and creatinine. Twenty-four hours after glycerol injection the total amount of cytochrome P-450 and b5 significantly decreased in renal but increased in liver microsomal fractions. Moreover, 48 and 72 hours after glycerol injection the level of cytochrome P-450 and b5 significantly increased in both organs. A single dose of DEPH (2 ml x kg(-1), i.p.) also elevated the total cytochrome P-450 and b5 in control animals. This enhancing effect of DEPH was additive to that of glycerol in glycerol-induced acute renal failure. These results indicate that DEPH and glycerol evoked pathological changes may affect the metabolism of xenobiotics plus endogenous hormones in the liver and in kidney.
Kertai
E
E
Department of Pharmaceutical Technology, University of Debrecen, Hungary.
Hollósi
G
G
Kovács
J
J
Varga
V
V
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001711:Biotransformation; D003404:Creatinine / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005990:Glycerol; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009212:Myoglobinuria / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000473:pathology; D014508:Urea / Q000097:blood; D015262:Xenobiotics / Q000493:pharmacokinetics*
D015262:Xenobiotics; D014508:Urea; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D003404:Creatinine; D004051:Diethylhexyl Phthalate; D005990:Glycerol