Acute zinc administration prolongs hexobarbitone-induced sleeping time in C57/6J mice

Two experiments were carried out in this study to demonstrate the effects of acute intraperitoneal (i.p.) administration of zinc chloride (ZnCl2) on hexobarbitone-induced sleeping time (HST) in female C57/6J mice. Serum and hepatic zinc content as well as hepatic cytochrome P450 content were also estimated in ZnCl2-treated and control mice. The ZnCl2 dose used was equal to the LD50 for chronic treatment (which was 28 micrograms g-1 body weight for mice given i.p. ZnCl2 five times a week for 3 weeks), determined in an earlier experiment. ZnCl2 injections at this dose were either given singly (in experiment I) or repeated on two mornings (in experiment II). Hexobarbitone, an ultra-short-acting experimental barbiturate, was given intraperitoneally 30 min after the single ZnCl2 injection in experiment I and 24 h after the second ZnCl2 injection in experiment II. Appropriate controls were given i.p. normal saline in each experiment. The HST was observed for all the animals, using the time-points at which the loss and regain of righting reflex occurred as the parameters. The animals were later killed; their blood and livers were obtained for estimation of zinc levels and cytochrome P450 content. The results of both experiments showed that ZnCl2 had caused a significant prolongation of the HST in C57/6J mice. Serum and hepatic zinc content were also elevated in both groups of ZnCl2-treated mice compared to their respective controls. The cytochrome P450 content in the single-dose ZnCl2-treated mice was unchanged while it was significantly reduced in the double-dose ZnCl2-treated mice when compared to the content in their respective controls. These findings suggest that acute zinc excess has an inhibitory effect on the function as well as the synthesis of hepatic cytochrome P450 enzymes.