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  • Title: Protective effect of central thyrotropin-releasing hormone on carbon tetrachloride-induced acute hepatocellular necrosis in rats.
    Author: Sato Y, Yoneda M, Nakamura K, Makino I, Terano A.
    Journal: J Hepatol; 2003 Jul; 39(1):47-54. PubMed ID: 12821043.
    Abstract:
    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 (CCl(4))-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 CCl(4) (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 CCl(4). RESULTS: Intracisternal TRH dose-dependently inhibited elevation of serum alanine aminotransferase level induced by CCl(4). Intracisternal TRH reduced CCl(4)-induced hepatic histological changes. The cytoprotective effect of central TRH on CCl(4)-induced acute hepatocellular necrosis was abolished by hepatic branch vagotomy, atropine, indomethacin and N(G)-nitro-L-arginine methyl ester, but not by 6-hydroxydopamine. Intravenous TRH did not influence CCl(4)-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.
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