Abstract
Biochemical and morphological studies of rat lung were performed to determine the role of lipid peroxidation in the in vivo lung toxicity of paraquat. Two injections of 20 mg/kg paraquat were administered intraperitoneally every other day. While notable epithelial damage in the lungs was observed on the day after the second paraquat injection and progressed through the 5th day, the concentration of lipid peroxides in the rat lungs did not increase by the 3rd day after the injection. The lipid peroxide concentrations increased after the 5th day post-injection, and reached the maximum concentrations on the 7th day, when the damaged alveolar surface had been mostly repaired by regenerative pneumocytes. On the other hand, the delayed increase of lung lipid peroxides in paraquattreated rats paralleled the increased number of macrophages in the lung, which reached maximum numbers on the 7th day. Glutathione peroxidase activity in the lungs also increased with a similar time course. Macrophages from the lungs contained a large amount of engulfed degradation products and cellular debris, and immunohistochemical study showed high glutathione peroxidase content on the 5th and 7th days. These results suggest that lipid peroxidation is a relatively late event in the in vivo paraquat-treated lung and that the delayed increase of lipid peroxides in the lungs occurs from the phagocytic activities of macrophages rather than from toxic cell injury.
Similar content being viewed by others
References
Bus JS, Aust SD, Gibson JE (1974) Superoxide- and singlet oxygencatalyzed lipid peroxidation as a possible mechanism for paraquat toxicity. Biochem Biophy Res Commun 58: 749–755
Bus JS, Aust SD, Gibson JE (1975) Lipid peroxidation: a possible mechanism for paraquat toxicity. Res Commun Chem Pathol Pharmacol 11: 31–38
Bus JS, Cagen SZ, Olgaard M, Gibson JE (1976) A mechanism of paraquat toxicity in mice and rats. Toxicol Appl Pharmacol 35: 501–513
Bus JS, Aust SD, Gibson JE (1977) Lipid peroxidation as a proposed mechanism for paraquat toxicity. In: Autor AP (ed) Biochemical mechanism of paraquat toxicity. Academic Press, New York, p 157
Farrington JA, Ebert M, Land EJ, Fletcher K (1973) Bipyridylium quaternary salts and related compounds. V. Pulse radiolysis studies of the action of paraquat radical with oxygen. Implication for the mode of action of BH. Biochem Biophys Acta 314: 372–381
Fukuda Y, Ferrans VJ, Schoenberger CI, Rennars SI, Crystal RG (1985) Patterns of pulmonary structural remodeling after experimental paraquat toxicity. The morphogenesis of intra-alveolar fibrosis. Am J Pathol 118: 452–475
Gee JBL, Khandwals AS (1976) Oxygen metabolism in the alveolar macrophage; friend or foe? J Reticuloendothel Soc 19: 229–236
Gee JBL, Vassallo CL, Bell P, Kaskin J, Basford RE, Field JB (1970) Catalase-dependent peroxidative mechanism in the alveolar macrophage during phagocytosis. J Clin Invest 49: 1280–1287
Greenberg DB, Reiser KM, Last JA (1978) Correlation of biochemical and morphologic manifestation of acute pulmonary fibrosis in rats administered paraquat. Chest 74: 421–425
Holmes RS, Masters CJ (1970) Epigenetic interconversion of the multiple forms of mouse liver catalase. FEBS Lett 11: 45–48
Ilett KF, Stripp B, Menard RH, Reid WD, Gillett JR (1974) Studies on the mechanism of the lung toxicity of paraquat: comparison of tissue distribution of some biochemical parameters in rats and rabbits. Toxicol Appl Pharmacol 28: 216–226
Keeling PL, Smith LL (1982) Relevance of NADPH depletion and mixed disulfide formation in rat lung to the mechanism of cell damage following paraquat administration. Biochem Pharmacol 31: 3243–3249
Kornburst DJ, Mavis RD (1980) The effect of paraquat on microsomal lipid peroxidation in vitro and in vivo. Toxicol Appl Pharmacol 34: 1841–1843
Misra HP, Gorsky LD (1981) Paraquat and NADPH-dependent lipid peroxidation in lung microsomes. J Biol Chem 256: 9994–9998
Modee J, Ivemark BI, Robertson B (1972) Ultrastructure of the alveolar wall in experimental paraquat poisoning. Acta Pathol Microbiol Scand 80: 50–54
Nerlich AG, Nerlich ML, Langer I, Demling RH (1984) Release of amino-terminal procollagen peptides in paraquat-induced acute pulmonary fibrosis. Exp Mol Pathol 40: 311–319
Ohkawa H, Ohishi N, Yage K (1979) Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95: 351–358
Omaye ST, Reddy KA, Cross CE (1978) Enhanced lung toxicity of paraquat in selenium-deficient rats. Toxicol Appl Pharmacol 43: 237–247
Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158–169
Plaa GL, Witschi H (1976) Chemicals, drugs and lipid peroxidation. Ann Rev Pharmacol Toxicol 16: 125–141
Reasor MJ, Koshut RA (1980) Augmentation in antioxidant defense mechanisms in rat alveolar macrophages following induction of phospholipidosis with chlorphentermine. Toxicol Appl Pharmacol 55: 334–341
Schoenberger CI, Rennard SI, Bitterman PB, Fukuda Y, Ferrans VJ, Crystal RG (1984) Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulation the development of fibrosis. Am Rev Respir Dis 129: 168–173
Sharp CW, Ottolenghi A, Posner HS (1972) Correlation of paraquat toxicity with tissue concentrations and weight loss of the rat. Toxicol Appl Pharmacol 22: 241–251
Shu H, Talcott RE, Rice SA, Weil ET (1979) Lipid peroxidation and paraquat toxicity. Biochem Pharmacol 28: 327–331
Smith P, Heath D (1973) The ultrastructure and time sequence of the early stages of paraquat lung in rats. J Pathol 114: 177–184
Smith P, Heath D (1976) Paraquat. CRC Crit Rev Toxicol 4: 411–445
Steffen C, Netter KJ (1979) On the mechanism of paraquat action on microsomal oxygen reduction and its relation to lipid peroxidation in experimental paraquat poisoning. NaunynSchmiedebergs Arch Pharmacol 310: 241–243
Sykes BI, Purchase FH, Smith LL (1977) Pulmonary ultrastructure after oral and intravenous dosage of paraquat to rats. J Pathol 121: 233–241
Thaw HH, Forslid J, Hamberg H, Hed J (1984) The effect of reactive oxygen metabolites on the attachment and ingestion phases of C3b- and IgG-mediated phagocytosis by macrophages. Acta Pathol Microbiol Immunol Scand Sect A 92: 1–8
Trush MA, Mimnaugh EG, Ginsburg E, Gram TE (1981) In vitro stimulation by paraquat of reactive oxygen-mediated lipid peroxidation on rat lung microsomes. Toxicol Appl Pharmacol 60: 279–296
Trush MA, Mimnaugh EG, Gram TE (1982) Activation of pharmacologic agents to radical intermediates. Implications for the role of free radicals in drug action and toxicity. Biochem Pharmacol 31: 3335–3346
Vijeyaratnam GS, Corrin B (1971) Experimental paraquat poisoning: a histological and electron-optical study of the changes in the lung. J Pathol 103: 123–129
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ogata, T., Manabe, S. Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats. Arch Toxicol 64, 7–13 (1990). https://doi.org/10.1007/BF01973370
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01973370