Protective effect of central thyrotropin-releasing hormone on carbon tetrachloride-induced acute hepatocellular necrosis in rats.
OBJECTIVE
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.
Sato
Yoichi
Y
Second Department of Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan.
Yoneda
Masashi
M
Nakamura
Kimihide
K
Makino
Isao
I
Terano
Akira
A
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D008099:Liver / Q000294:innervation / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009336:Necrosis; D016627:Oxidopamine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014628:Vagotomy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D010276:Parasympatholytics; D013565:Sympatholytics; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D001285:Atropine; D016627:Oxidopamine; D002251:Carbon Tetrachloride; D011761:Pyrrolidonecarboxylic Acid; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin