Protective effect of aminoguanidine, a nitric oxide synthase inhibitor, against carbon tetrachloride induced hepatotoxicity in mice.
The present study was undertaken to evaluate the effect of aminoguanidine (AG) on carbon tetrachloride (CCl4)-induced hepatotoxicity. Treatment of mice with CCl4 (20 microl/kg, i.p.) resulted in damage to centrilobular regions of the liver, increase in serum aminotransferase and rise in lipid peroxides level 24 hours after CCl4 administration. Pretreatment of mice with AG (50 mg/kg, i.p.) 30 minutes before CCl4 was found to protect mice from the CCl4-induced hepatic toxicity. This protection was evident from the significant reduction in serum aminotransferase, inhibition of lipid peroxidation and prevention of CCl4-induced hepatic necrosis revealed by histopathology. Aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, did not inhibit the in vitro lipid peroxidation. Taken together, these data suggest a potential role of nitric oxide as an important mediator of CCl4-induced hepatotoxicity.
Al-Shabanah
O A
OA
Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia. shabanah@ksu.edu.sa
Alam
K
K
Nagi
M N
MN
Al-Rikabi
A C
AC
Al-Bekairi
A M
AM
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D006146:Guanidines; D002084:Butylated Hydroxytoluene; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; C004479:pimagedine