Ayman M. Gamal el-Din
Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia
Abdulhakeem A. Al-Majed
Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia
Abdulaziz A. Al-Yahya
Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia
Abdullah M. Al-Bekairi
Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia
Adel M. Mostafa
Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia
ABSTRACT
The present study was undertaken to evaluate whether stimulation or inhibition of Nitric Oxide (NO) synthesis could affect lung toxicity induced by acute administration of paraquat (PQ) in mice. L-arginine (L-arg.), NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) were employed as NO precursor, competitive and specific NO synthesis inhibitors, respectively. PQ was administered intraperitoneally to Swiss albino mice at a single dose of 50 mg kg-1. L-arg. (700 mg kg-1 day-1), L-NAME (150 mg kg-1 day-1) or AG (100 mg kg-1 day-1) was given in drinking water of mice for 5 days before and one day after PQ administration. Appropriate controls were performed. PQ administration resulted in a pronounced elevation in lipid peroxides (157%) as well as decreased activity of alkaline phosphatase [ALP] (48%) and non-protein thiols (40%) in lung tissue compared to control non-treated mice as evidences of lung injury. Serum level of NO end products, nitrate and nitrite significantly elevated due to PQ administration (150%) as compared to control level. In mice given combined treatment of L-arg. and PQ, a remarkable rise in the serum level of nitrate and nitrite (140%) compared to the PQ group was observed. In addition, L-arg. ameliorated the increased level of lipid peroxides and non-protein thiols depletion as well as the decreased activity of ALP caused by PQ respectively. On the other hand, L-NAME and AG potentiated the deleterious effects of PQ on serum NO, lung lipid peroxides content, non-protein thiols content and alkaline phosphatase activity. In conclusion, PQ-induced lung injury in mice is alleviated by L-arg. but exacerbated by L-NAME and AG supplementation. This could point out to a possible protective role of NO in PQ lung toxicity.
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How to cite this article
Ayman M. Gamal el-Din, Abdulhakeem A. Al-Majed, Abdulaziz A. Al-Yahya, Abdullah M. Al-Bekairi and Adel M. Mostafa, 2005. A Possible Modulatory Role of Nitric Oxide in Paraquat-induced Lung Injury in Mice. International Journal of Pharmacology, 1: 360-365.
DOI: 10.3923/ijp.2005.360.365
URL: https://scialert.net/abstract/?doi=ijp.2005.360.365
DOI: 10.3923/ijp.2005.360.365
URL: https://scialert.net/abstract/?doi=ijp.2005.360.365
REFERENCES
- Moncada, S., R.M.J. Palmer and E.A. Higgs, 1991. Nitric oxide physiology pathophysiology and pharmacology. Pharmacol. Rev., 43: 109-142.
PubMed - Pryor, W.A. and G.L. Squadrito, 1995. The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide. Am. J. Physiol., 12: L699-L722.
Direct Link - Paget, G.E. and J.M. Barnes, 1964. Evaluation of Drug Activities. In: Pharmacometrics, Lawrence, D.R. and A.L. Bacharach (Eds.). Vol. 1, Academic Press, New York, pp: 160-167.
Direct Link - Nogawa, S., C. Forster, F. Zhang, M. Nagayama, M.E. Ross and C. Iadecola, 1998. Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia. Proc. Natl. Acad. Sci. USA., 95: 10966-11971.
PubMedDirect Link - Melchiorri, D., R.J. Reiter, E. Sewerynek, M. Hara, L. Chen and G. Nistico, 1996. Paraquat toxicity and oxidative damage: Reduction by melatonin. Biochem. Pharmacol., 51: 1095-1099.
CrossRefDirect Link - Ohkawa, H., N. Ohishi and K. Yagi, 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 95: 351-358.
CrossRefPubMedDirect Link - Ellman, G.L., 1959. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 82: 70-77.
CrossRefPubMedDirect Link - Belfield, A. and D.M. Goldberg, 1971. Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme, 12: 561-573.
PubMedDirect Link - Miranda, K.M., M.G. Espey and D.A. Wink, 2001. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 5: 62-71.
CrossRefDirect Link - Eisenman, A., Z. Armali, B. Raikhlin-Eisenkraft, L. Bentur, Y. Bentur, L. Guralink and R. Enat, 1998. Nitric oxide inhalation for paraquat-induced lung injury. J. Toxicol. Clin. Toxicol., 36: 585-586.
Direct Link - Muriel, P., 1998. Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation and liver damage induced by carbon tetrachloride. Biochem. Pharmacol., 56: 773-779.
PubMedDirect Link