A mechanism of paraquat toxicity in mice and rats

doi:10.1016/0041-008X(76)90073-9

Toxicology and Applied Pharmacology

Volume 35, Issue 3, March 1976, Pages 501-513

https://doi.org/10.1016/0041-008X(76)90073-9 Get rights and content

Abstract

The purpose of this study was to investigate the hypothesis that paraquat toxicity results from cyclic reduction-oxidation of paraquat in vivo, with subsequent generation of superoxide radicals and initiation of lipid peroxidation. Phenobarbital pretreatment (0.1% in drinking water for 10 days) significantly increased the paraquat LD50 in mice, but only when the mice were continued on phenobarbital after paraquat administration. Phenobarbital, through its own metabolism, may be competing for electrons which might otherwise be utilized in paraquat reduction and thus decrease paraquat toxicity. Paraquat, given at 30 mg/kg ip to mice, significantly decreased liver concentrations of the water-soluble antioxidant, reduced glutathione, and lung concentrations of lipid-soluble antioxidants. The decrease in tissue antioxidants may reflect the initiation of lipid peroxidation by paraquat. Oxygen-tolerant rats (exposure to 85% oxygen for 7 days) have increased activities of pulmonary enzymes which combat lipid peroxidation. The paraquat Lt50 (median time to death) after 45 mg/kg of paraquat ip was significantly increased in oxygentolerant rats compared to room-air-exposed controls. Rats exposed to 100 ppm paraquat in the drinking water for 3 weeks had significantly elevated activities of lung glucose-6-phosphate dehydrogenase and glutathione reductase. The cross-tolerance of oxygen and paraquat and the induction by paraquat of pulmonary enzymes that supply reducing equivalents to combat oxidative damage support the proposal that paraquat may initiate lipid peroxidation in vivo.

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Citation Excerpt :
This is supported by the fact that either activation of AMPK (AICAR) or inhibition of mTOR (rapamycin) can negate the protection of TLR4 deficiency against paraquat-induced cardiomyocyte contractile dysfunction. Paraquat toxicity has long been employed as a rodent model for oxidative stress (Bus et al., 1976; Day and Crapo, 1996). ROS accumulation and oxidative stress have been speculated to underscore paraquat poisoning along with pro-inflammatory injury (Brooks, 1971; Bus et al., 1974).
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¹: Present address: Department of Environmental Health, Kettering Laboratory, University of Cincinnati, Cincinnati, Ohio 45267.

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A mechanism of paraquat toxicity in mice and rats

Abstract

Life Sci.

Toxicol. Appl. Pharmacol.

Biochem. Biophys. Res. Commun.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

J. Nutr.

Biochim. Biophys. Acta

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Exp. Mol. Pathol.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Accidental poisoning by paraquat: Report of two cases in man

Brit. Med. J.

Lipid peroxidation: A possible mechanism for paraquat toxicity

Res. Commun. Chem. Pathol. Pharmacol.

An enzymatic protective mechanism against lipid peroxidation damage to lungs of ozone-exposed rats

Lipids

The toxicity of paraquat

Brit. J. Ind. Med.

A fluorometric assay for glutathione

Anal. Biochem.

Fatal pulmonary intraalevolar fibrosis after paraquat ingestion

N. Engl. J. Med.