Studies on the mechanism of the lung toxicity of paraquat: Comparison of tissue distribution and some biochemical parameters in rats and rabbits

Ilett, Kenneth F.; Stripp, Bitten; Menard, Raymond H.; Reid, Watson D.; Gillette, James R.

doi:10.1016/0041-008x(74)90007-6

Cited by 147 publications

(20 citation statements)

References 21 publications

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“…Carbon tetrachloride also causes lipid peroxidation and liver necrosis (28), but some of its metabolites bind covalently in the liver cell, and it is not clear presently what the relative roles of lipid peroxidation and covalent binding are in the liver necrosis due to it. Covalent binding is not known to occur with paraquat and diquat (29).…”

Section: Discussionmentioning

confidence: 99%

Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

Burk¹,

Lawrence²,

Lane³

1980

J. Clin. Invest.

265

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A B S T R A C T Paraquat and diquat facilitate formation of superoxide anion in biological systems, and lipid peroxidation has been postulated to be their mechanism of toxicity. Paraquat has been shown to be more toxic to selenium-deficient mice than to controls, presumably as the result of decreased activity of the selenoenzyme glutathione peroxidase. The present study was designed to measure lipid peroxidation and to assess toxicity in control and selenium-deficient rats given paraquat and diquat. Lipid peroxidation was measured by determining ethane production rates of intact animals; toxicity was assessed by survival and by histological and serum enzyme evidence of liver and kidney necrosis. Paraquat and diquat were both much more toxic to selenium-deficient rats than to control rats. Diquat (19.5 umol/kg) caused rapid and massive liver and kidney necrosis and very high ethane production rates in selenium-deficient rats. The effect of paraquat (78 ,umol/kg) was similar to that of diquat but was not as severe. Acutely lethal doses of paraquat (390 ,umol/kg) and diquat (230 ,umol/kg) in control rats caused very little ethane production and no evidence of liver necrosis. These findings suggest that paraquat and diquat exert their acute toxicity largely through lipid peroxidation in selenium-deficient rats. Selenium deficiency had no effect on superoxide dismutase activity in erythrocytes or in 105,000 g supernate of liver or kidney. Glutathione peroxidase, which represents the only well-characterized biochemical function of selenium in animals, was dissociated from the protective effect of selenium against diquat-induced lipid peroxi-

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Section: Discussionmentioning

confidence: 99%

Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

Burk¹,

Lawrence²,

Lane³

1980

J. Clin. Invest.

265

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“…Redox cycling of paraquat not only results in an uncoupling of microsomal electron transport (76) but also rapidly consumes NADPH and oxygen. All three of these effects would be expected to readily inhibit NADPH-dependent lipid peroxidation, which possibly accounts for the observations in many of the in vitro studies (25,26,71,72). The possibility that paraquat would stimulate microsomal lipid peroxidation if adequate precautions were taken to maintain both NADPH and oxygen concentrations in the incubate has in fact been demonstrated (77,78).…”

Section: Paraquat-induced Lipid Peroxidationmentioning

confidence: 99%

“…As indicated in several studies described above (24,25), the oxidation of reduced paraquat generated by mammalian tissues results in the apparent formation of hydrogen peroxide. Several studies have indicated that this reaction proceeds via formation of the single electron reduction product of molecular oxygen, O2 , as had been proposed from pulse radiolysis studies (23,36).…”

Section: Mechanisms Of Paraquattoxicity Redox Cycling Of Paraquatmentioning

confidence: 99%

“…Ilett et al. (25) reported that paraquat inhibited rat lung microsomal lipid peroxidation, even though paraquat stimulated both NADPH oxidation and hydrogen peroxide formation. Subsequent investigations have confirmed an in vitro paraquat inhibition of lipid peroxidation in microsomes isolated from rat lung and liver (71,72) and mouse liver (26).…”

Section: Paraquat-induced Lipid Peroxidationmentioning

confidence: 99%

“…In 1968, Gage (24) reported that anaerobic incubation of liver microsomes with NADPH (25)(26)(27) and lung (25,28,29) microsomal hydrogen peroxide production, as measured by the conversion of methanol to formaldehyde. These observations again suggested the potential for a two-electron reduction of molecular oxygen catalyzed by paraquat.…”

Section: Mechanisms Of Paraquattoxicity Redox Cycling Of Paraquatmentioning

confidence: 99%

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Paraquat: model for oxidant-initiated toxicity.

Bus¹,

Gibson²

1984

Environ Health Perspect

502

238

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Paraquat, a quaternary ammonium bipyridyl herbicide, produces degenerative lesions in the lung after systemic administration to man and animals. The pulmonary toxicity of paraquat resembles in several ways the toxicity of several other lung toxins, including oxygen, nitrofurantoin and bleomycin. Although a definitive mechanism of toxicity of paraquat has not been delineated, a cyclic single electron reduction/oxidation of the parent molecule is a critical mechanistic event. The redox cycling of paraquat has two potentially important consequences relevant to the development of toxicity: generation of "activated oxygen" (e.g., superoxide anion, hydrogen peroxide, hydroxyl radical) which is highly reactive to cellular macromolecules; and/or oxidation of reducing equivalents (e.g., NADPH, reduced glutathione) necessary for normal cell function. Paraquat-induced pulmonary toxicity, therefore, is a potentially useful model for evaluation of oxidant mechanisms of toxicity. Furthermore, characterization of the consequences of intracellular redox cycling of xenobiotics will no doubt provide basic information regarding the role of this phenomena in the development of chemical toxicity.

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Acceleration of Lipid Peroxidation in Human Paraquat Poisoning

Yasaka¹

1981

Arch Intern Med

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Studies on the mechanism of the lung toxicity of paraquat: Comparison of tissue distribution and some biochemical parameters in rats and rabbits

Cited by 147 publications

References 21 publications

Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

Paraquat: model for oxidant-initiated toxicity.

Acceleration of Lipid Peroxidation in Human Paraquat Poisoning

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