Skip to main content

Advertisement

Log in

Decreasing the oxidant stress from paraquat in isolated perfused rat lung using captopril and niacin

  • Organ Toxicity and Mechanisms
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

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 μM), captopril (10 μM) and PQ (600 μM) 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 μM) and niacin (150 μM) 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aldrich TK, Fisher AB, Candes E, Chance B (1983) Evidence for lipid peroxidation by paraquat in the perfused lung. Lab Invest 60:473–485

    Google Scholar 

  • Aroma OI, Akanmu D, Cecchini R, Halliwell B (1991) Evaluation of the ability of the angiotensin-converting enzyme inhibitor captopril to scavenge reactive oxygen species. Chem Biol Interact 77:303–314

    Google Scholar 

  • Barabas K, Serenyl P, Saelypes A (1990) Inhibition of lung damage caused by paraquat with lymphokines or cytokines. Exp Pathol 38:189–195

    Google Scholar 

  • Bieri JG, Corash L, Hubbard VS (1983) Medical uses of vitamin E. N Engl J Med 308:1063–1071

    Google Scholar 

  • Boobis AR, Fawthrop DJ, Davies DS (1989) Mechanisms of cell death. Trends Pharmacol Sci 10:275–280

    Google Scholar 

  • Bus JS, Gibson JE (1984) Paraquat: model for oxidant initiated toxicity. Environ Health Perspect 55:37–46

    Google Scholar 

  • Carre P, Leophone P (1993) Cytokines in pulmonary fibrosis. Rev Mal Respir 10:193–207

    Google Scholar 

  • Chaturvedi P (1995) Isis-4 (Fourth International Study of Infarct Survival) Collaborative Group. A randomized factorial trial assessing early oral captopril, oral momonitrate and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction. Lancet 345:669–685

    Google Scholar 

  • Chopra MH, Beswick M, Clapperton HJ, Dargie WE, Smith McMurray J (1992) Antioxidant effects of angiotensin-converting (ACE) inhibitors: free radical and antioxidant scavenging are sulfhydryl dependent, but lipid peroxidation is inhibited by both sulfhydryl- and nonsulfhydryl-containing ACE inhibitors. J Cardiovascular Pharmacol 19:330–340

    Google Scholar 

  • Copland GM, Kolin A, Shulman HS (1974) Fatal pulmonary intraalveolar fibrosis after paraquat ingestion. N Engl J Med 291:290–292

    Google Scholar 

  • de Cavanagh EMV, Inserra F, Ferder L, Romano L, Ercole L, Fraga CG (1995) Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver. FEBS Lett 361:22–24

    Google Scholar 

  • de Cavanagh EMV, Fraga CG, Ferder L, Inserra F (1997) Enalapril and captopril enhance antioxidant defenses in mouse tissues. Am J Physiol Regul Integr Comp Physiol 272:R514–R518

    Google Scholar 

  • Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Google Scholar 

  • Ferder L, Inserra F, Romano L, Ercole L, Pszenny V (1993) Effects of angiotensin-converting enzyme inhibition on mitochondrial number in the aging mouse. Am J Physiol Cell Physiol 265:C15–C18

    Google Scholar 

  • Fritz KL, Nelson TL, Ruiz-Velasco V, Mercurio SD (1994) Acute intramuscular injection of oils or the oleic acid component protects mice against PQ lethality. J Nutr 124:425–429

    Google Scholar 

  • Ghazi-Khansari M, Dorchehzadeh Sh, Rezayat M (2001) The treatment of paraquat-induced lung fibrosis using captopril and niacin. Proceedings of the 3rd International Congress of the Asia-Pacific Association of Medical Toxicology, 12–15 November 2001, Penang, Malaysia, p 71

  • Gohlke P, Unger T (1995) Chronic low-dose treatment with perindopril improves cardiac function in stroke-prone spontaneously hypertensive rats by potentiation of endogenous bradykinin. Am J Cardiol 76:41E–45E

    Google Scholar 

  • Grover GJ, Sleph PG, Dzwonzyk S, Wang P, Tobias DO (1991) Effects of different angiotensin-converting enzyme (ACE) inhibitors on ischemic isolated rat hearts: relationship between cardiac ACE inhibition and cardioprotection. J Pharmacol Exp Ther 257:919–929

    Google Scholar 

  • Kojima S, Miyazaki Y, Honda T, Kiyozumi M, Shimada H, Funakoshi T (1992) Effect of L-cystine on toxicity of paraquat in mice. Toxicol Lett 60:75–82

    Google Scholar 

  • Kuo CH, Hook JB (1982) Depletion of renal gluthathione content and nephrotoxicity of cephaloridine in rabbit, rats, mice. Toxicol Appl Pharmacol 63:292–302

    Google Scholar 

  • Lasky JA, Ortiz LA (2001) Antifibrotic therapy for the treatment of pulmonary fibrosis. Am J Med Sci 332:213–218

    Google Scholar 

  • Mak IT, Freedman AM, Dickens BF, Weglicki WB (1990) Protective effects of sulfhydryl-containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells. Biochem Pharmacol 40:2169–2175

    Google Scholar 

  • Masahico S, Akira N, Nabumasa I (1992) Effect of preinduction of metallothionein on paraquat toxicity in mice. Arch Toxicol 66:145–148

    Google Scholar 

  • Mehendale HM, Angevine LS, Ohmiya Y (1981) The isolated perfused lung—a critical evaluation. Toxicology 21:1–36

    Google Scholar 

  • Mira ML, Silva M, Queiroz MJ, Manse CF (1993) Angiotensin converting enzyme inhibitors as oxygen free radical scavengers. Free Radic Res Commun 19:173–181

    Google Scholar 

  • Misik V, Mak IT, Stafford RE, Weglicki WB (1993) Reactions of captopril and epicaptopril with transition metal ions and hydroxyl radicals: an EPR spectroscopy study. Free Radic Res Commun 15:611–619

    Google Scholar 

  • Murray RE, Gibson JE (1972) A comparative study of paraquat intoxication in rats, guinea pigs and monkey. Exp Mol Pathol 17:317–325

    Google Scholar 

  • Ohishi T, Saito H, Tsusaka K, Toda K, Inagaki H, Hamada Y, Kumagai N, Atsukawa K, Ishii H (2001) Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats. Hepatol Res 21:147–158

    Google Scholar 

  • Perriens JH, Benimadho S, Kiauw IL, Wisse J, Chee H (1992) High-dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective study. Hum Exp Toxicol 11:129–139

    Google Scholar 

  • Reed DJ (1990) Glutathione toxicology implications. Annu Rev Pharmacol Toxicol 30:603–631

    Google Scholar 

  • Salmona M, Donnini M, Perin L, Diomede L, Romano M, Marini MG, Tacconi MT, Luisetti M (1992) A novel pharmacological approach for paraquat poisoning in rat and A549 cell line using ambroxol, a lung surfactant synthesis inducer. Food Chem Toxicol 30:789–794

    Google Scholar 

  • Smith LL (1988) The toxicity of paraquat. Adverse Drug React Acute Poisoning Rev 1:1–17

    Google Scholar 

  • Smith LL, Rose MS (1977) A comparison of the effect of paraquat and diquat on the water content of rat lung incorporation of thymidine into lung DNA. Toxicology 8:223

    Google Scholar 

  • Suntres ZE, Hepworth SR, Shek PN (1992) Protective effect of liposome-associated α-tocopherol against paraquat-induced acute lung toxicity. Biochem Pharmacol 44:1811–1818

    Google Scholar 

  • Virjeyaratnam GS, Corrin B (1971) Experimental paraquat poisoning: a histological and electron-optical study of the changes in the lung. J Pathol 103:123–129

    Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the advice and useful statistical comments provided by Dr. Hamed Shafarodie and Lila Moezi.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahmoud Ghazi-Khansari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghazi-Khansari, M., Nasiri, G. & Honarjoo, M. Decreasing the oxidant stress from paraquat in isolated perfused rat lung using captopril and niacin. Arch Toxicol 79, 341–345 (2005). https://doi.org/10.1007/s00204-004-0632-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-004-0632-6

Keywords

Navigation