Cadmium exposure decreases androgen-dependent metabolism of acetohexamide in liver microsomes of male rats through its testicular toxicity

Abstract

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.

Modulatory effects of lipoic acid and selenium against cadmium-induced biochemical alterations in testicular steroidogenesis

“…After 2 weeks of acclimatization, the rats were divided into four groups of 10 animals each. Group 1 received saline (vehicle, i.p) and served as control, the remaining three groups were given either (i) CdCl 2 (2 mg/kg, i.p, daily for 28 days) 15; (ii) CdCl 2 + lipoic acid (35 mg/kg; p.o) 13 or (iii) CdCl 2 + selenium (Se) (as sodium selenite, 0.35 mg/kg, p.o.) 16 from the first day of CdCl 2 injection for consecutive 28 days.…”