Alpha(1)-Adrenoceptor antagonists prevent paracetamol-induced hepatotoxicity in mice.

ABSTRACT:

Background and purpose

Paracetamol, a major cause of acute liver failure (ALF) represents a significant clinical problem. Adrenoceptor stimulation or antagonism can modulate chemical-induced hepatotoxicity. We investigated the role of endogenous catecholamines and alpha(1)-adrenoceptors in the development of paracetamol- induced hepatotoxicity.

Experimental approach

Paracetamol (3.5 mmol kg(-1)) was administered to male CD-1 mice, with and without alpha(1)-adrenoceptor antagonists (prazosin, doxazosin, terazosin and tamsulosin; 35.7 micromol kg(-1)). Serum transaminases and hepatic glutathione (GSH) levels were assessed as markers of hepatic damage. Paracetamol bioactivation was assessed by covalent binding, hepatic and urinary conjugate formation and uridine glucuronosyltra

SUBMITTER: Randle LE 

PROVIDER: S-EPMC2259197 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature