Cadmium exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity.
Administration of cadmium (Cd) at a dose of 1.23 mg/kg (2.0 mg/kg as CdCl(2)) markedly decreased the activity of an enzyme (acetohexamide reductase) catalysing the ketone-reduction of acetohexamide, an oral antidiabetic drug, in liver microsomes of male rats. However, the decreased enzyme activity was increased by repeated treatment with testosterone propionate (TP). When male rats were castrated and TP was given to the castrated ones, a similar decrease and increase, as described above, were observed in the microsomal enzyme activity. Cd exposure to male rats induced haemorrhage and atrophy of the testes and significantly diminished serum testosterone levels. There was no possibility that Cd accumulated in liver microsomes of male rats causing direct inhibition of the microsomal enzyme activity. We conclude that Cd exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity. Cd exposure had no effect on acetohexamide reductase activity in liver cytosol of male rats.
Shimada
Hideaki
H
Faculty of Education, Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan.
Yamaguchi
Shizuka
S
Murata
Hideyuki
H
Otagiri
Masaki
M
Imamura
Yorishige
Y
D000092:Acetohexamide / Q000008:administration & dosage / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood* / Q000494:pharmacology
D007004:Hypoglycemic Agents; D002104:Cadmium; D013739:Testosterone; D000429:Alcohol Oxidoreductases; C064152:acetohexamide reductase; D000092:Acetohexamide