Lisinopril ameliorates paraquat-induced lung fibrosis.
BACKGROUND
Paraquat is a controversial and one of the most commonly used herbicides in the world. Although liver, kidney, heart and CNS are affected, lung damage resulting to pulmonary fibrosis is the usual cause of deaths in the cases with intoxication. The mechanism of paraquat toxicity is not clear but probably includes the induction of lipid peroxidation of unsaturated fatty acids. Lisinopril, an angiotensin-converting enzyme inhibitor (ACEI), an antihypertensive drug, has beneficial effects on the treatment of fibrosis. The antifibrotic effect of lisinopril has shown to be due to inhibition of synthesis of angiotensin II that causes stimulation of fibroblast proliferation and collagen synthesis.


METHODS
Male albino Wistar rats were used in the experiments (weighing 150-300 g). The animals were divided into 5 groups: group I received saline, group II received lisinopril (1 mg/kg; po), group III was given a single i.p. dose of 20 mg/kg paraquat, group IV (treatment group) received lisinopril after single a i.p. dose of 20 mg/kg paraquat, and group V (pre-treatment group) received lisinopril before a single i.p. dose of 20 mg/kg paraquat. After 21 days of treatment, the level of hydroxyproline and the degree of lipid peroxidation were determined in the lung tissue of the animals and the lungs were examined histologically for fibrosis.


RESULTS
Paraquat caused a significant increase in hydroxyproline content and lisinopril significantly decreased the amount hydroxyproline (p<0.001) in the lung tissue of the rats. The histological examination also indicated that lisinopril can effectively protect the paraquat-induced lung fibrosis. The lipid peroxidation levels in the lung were not significantly changed when compared to the control group.


CONCLUSIONS
The antifibrotic effect of lisinopril may be due to inhibition of angiotensin II or proline moiety, which is a common structural in all ACEI, drugs.
Mohammadi-Karakani
Ali
A
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P. O. Box 13145-784, Tehran, and Alborz Hospital, Social Security Organization, Karaj, Iran.
Ghazi-Khansari
Mahmoud
M
Sotoudeh
Masoud
M
D000818:Animals; D006909:Hydroxyproline / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D017706:Lisinopril / Q000494:pharmacology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D017706:Lisinopril; D010269:Paraquat; D006909:Hydroxyproline