Protective effect of BP 2-94, a histamine H3-receptor agonist prodrug, in a model of carbon tetrachloride-induced hepatotoxicity in rats.
BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)-alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero-protective properties in experimental animals.


OBJECTIVE
The aim of the present study was to investigate the effect of BP 2-94 in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats.


METHODS
In order to investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and 60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1), 4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days).


RESULTS
BP 2-94 in the tested doses did not cause significant changes in the plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities and the liver microscopic appearance was normal. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a pretreatment dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities in response to CCl4.


CONCLUSIONS
BP 2-94 had a hepatoprotective effect in a model of CCl4-induced toxicity in rats. This effect might be due the H3-agonistic activity of its active metabolite (R)-alpha-MeHA.
Valcheva-Kuzmanova
Stefka V
SV
Department of Preclinical and Clinical Pharmacology and Biochemistry, Medical University--Varna, Bulgaria.
Popova
Petia B
PB
Krasnaliev
Ivan J
IJ
Galunska
Bistra Tz
BT
Belcheva
Anna
A
Schunack
Walter
W
D000704:Analysis of Variance; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000517:prevention & control*; D017442:Histamine Agonists / Q000494:pharmacology*; D007097:Imines / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D017442:Histamine Agonists; D007097:Imines; D010636:Phenols; D011355:Prodrugs; C106714:BP 2-94