Possible role of metallothionein-Zn in protection against halothane-induced hepatotoxicity in rats

Abstract

A rat model of halothane-induced hepatotoxicity was produced by exposure of phenobarbital-pretreated male Wistar rats to halothane (0.5%) for two hours under conditions of hypoxia (10% oxygen). In this model elevated serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ornithine carbamoyltransferase (OCT) were observed. Hepatic injury was not apparent in any phenobarbital-pretreated rat exposed to halothane (0.5%) in 20% oxygen or to hypoxia alone (10% oxygen).
Administration of zinc sulfate (Zn: 1 or 2 mg/kg im) 24 hours prior to inhalation of halothane in 10% oxygen resulted in protection against halothane-induced hepatotoxicity. The release of GOT, GPT, and OCT into plasma was markedly lower in rats pretreated with zinc sulfate (1 or 2 mg/kg) than in saline pretreated rats.
At the same time, administration of a single dose (1 or 2 mg/kg) of zinc produced 380% and 800% increases in the hepatic concentration of metallothionein-Zn before exposure to halothane (0.5%) in 10% oxygen, respectively, and similar doses produced 45% and 30% decreases in the hepatic concentration of metallothionein-Zn following exposure to halothane (0.5%) in 10% oxygen for two hours, respectively.
This suggests that metallothionein-Zn may play a role in protection against halothane-induced hepatotoxicity.