Decreasing the oxidant stress from paraquat in isolated perfused rat lung using captopril and niacin.
The abilities of captopril and niacin to protect against the lung toxicity of paraquat (PQ) were studied. The anti-oxidative action of captopril, an angiotensin-converting enzyme inhibitor, appears to be attributable to the sulphahydryl group (SH) in the compound, which gives captopril the ability to scavenge reactive oxygen species. Niacin replenishes the NAD and ATP depletion caused by reactive oxygen species. PQ causes lung damage in man and in several species of laboratory animals. The damage is initially manifested by hemorrhage and edema, and later by consolidation of the lung and fibrosis development. In this study, the lungs of male Wistar rats (250-300 g in weight) were perfused by Krebs-Ringer buffer alone (control), niacin (150 microM), captopril (10 microM) and PQ (600 microM) in perfusion fluid, and the biochemical changes that occurred in isolated rat lung were examined within 1 h and compared to PQ alone. The results show that captopril significantly decreases the lung weight/body weight ratio when used as a pretreatment and a post-treatment to captopril (p<0.0001). The results also show that captopril (10 microM) and niacin (150 microM) significantly decreases PQ-induced lung toxicity. Lactate dehydrogenase (LDH) activity significantly decreased in treatment groups as compared to the PQ group (p<0.0001). This study suggests that paraquat causes increased lipid peroxidation and LDH activity and decreased glutathione (GSH) and total protein in isolated perfused rat lung. These effects are reduced under these experimental conditions by captopril and niacin.
Ghazi-Khansari
Mahmoud
M
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P. O. Box 13145-784, Tehran, Iran. ghazikha@sina.tums.ac.ir
Nasiri
Ghodratolla
G
Honarjoo
Marzyieh
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D009525:Niacin; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D010269:Paraquat