Protective effect of aminoguanidine against paraquat-induced oxidative stress in the lung of mice.
The effect of aminoguanidine (AG) against toxicity of paraquat (PQ), an oxidative-stress inducing substance, in mice was investigated. A single dose of PQ (50 mg/kg, i.p.) induced lung-toxicity, manifested by significant decrease of the activity of angiotensin converting enzyme (ACE) in lung tissue indicating pulmonary capillary endothelial cell damage. Lung toxicity was further evidenced by significant decrease of total sulfhydryl (-SH) content and significant increase in lipid peroxidation measured as malondialdehyde (MDA) in lung tissues. Oral pretreatment of mice with AG (50 mg/kg) in drinking water, starting 5 days before PQ injection and continuing during the experimental period, ameliorated the lung toxicity induced by PQ. This was evidenced by a significant increase in the levels of ACE activity, a significant decrease in lung MDA content and a significant increase in the total sulfhydryl content 24 h after PQ administration. Moreover, pretreatment of mice with AG leads to an increase of the LD(50) value of paraquat. These results indicate that AG is an efficient cytoprotective agent against PQ-induced lung toxicity.
Mustafa
Adel
A
Departments of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia.
Gado
Ali M
AM
Al-Shabanah
Othman A
OA
Al-Bekairi
Abdullah M
AM
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D006146:Guanidines / Q000494:pharmacology*; D006540:Herbicides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007928:Lethal Dose 50; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism
D006146:Guanidines; D006540:Herbicides; D009569:Nitric Oxide; D000469:Alkaline Phosphatase; D007703:Peptidyl-Dipeptidase A; D010269:Paraquat; C004479:pimagedine