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

Abstract

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-

The expression of melanin-based plumage is separately modulated by exogenous oxidative stress and a melanocortin

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Stress resistance and aging: Influence of genes and nutrition

“…Although CR can improve cytochrome P450-mediated detoxification in multiple tissues in rodents (Manjgaladze et al, 1993;Seng et al, 1996), there are no documented reports of P450 activities in Snell dwarf or GHR-KO mice, and inter-individual variation in cytochrome P450 activity can have a dramatic influence on the degree of toxininduced liver damage (Mathijssen and van Schaik, 2006). In addition, tests using APAP do not provide information about oxidation resistance in other tissues or to toxins that act through other pathways, such as the direct liver toxin, diquat (Burk et al, 1980) or the nephrotoxin gentamicin (Nakajima et al, 1994).…”

The effect of selenium deficiency on peroxidative injury in the house fly, Musca domestica

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