低酸素下ハロセン吸入によるラット肝障害モデルに対する亜鉛の保護作用に関する実験的研究

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.