Protective effect of central thyrotropin-releasing hormone on carbon tetrachloride-induced acute hepatocellular necrosis in rats

Background/Aims: Thyrotropin-releasing hormone (TRH) acts in the brain to stimulate hepatic proliferation and blood flow through vagal-muscarinic and prostaglandin-mediated pathways. Hepatic blood flow and prostaglandins are well recognized as cytoprotective factors for liver damage, and central TRH is known to play a role in gastric cytoprotection. The effect of central TRH on carbon tetrachloride (CCl4)-induced acute hepatocellular necrosis was investigated in rats. Methods: Male fasted rats were injected with either TRH analog, RX 77368 (1–10 ng), or vehicle intracisternally, and CCl4 (2.0 ml/kg) was injected subcutaneously 60 min later. Acute hepatocellular necrosis was assessed by serum hepatic enzymes and histological changes 24 h after CCl4. Results: Intracisternal TRH dose-dependently inhibited elevation of serum alanine aminotransferase level induced by CCl4. Intracisternal TRH reduced CCl4-induced hepatic histological changes. The cytoprotective effect of central TRH on CCl4-induced acute hepatocellular necrosis was abolished by hepatic branch vagotomy, atropine, indomethacin and NG-nitro- -arginine methyl ester, but not by 6-hydroxydopamine. Intravenous TRH did not influence CCl4-induced acute hepatocellular necrosis. Conclusions: These results suggest that the cytoprotective effect of central TRH on acute hepatocellular necrosis is mediated through vagal-muscarinic, and prostaglandin- and nitric oxide-dependent pathways.