Role of antioxidants in paraquat toxicity

Paraquat, a quarternary nitrogen herbicide, is a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The mechanisms of paraquat toxicity involve: the generation of the superoxide anion, which can lead to the formation...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2002-10, Vol.180 (1), p.65-77
Main Author: Suntres, Zacharias E
Format: Article
Language:English
Subjects:
Acetylcysteine - metabolism
Acetylcysteine - therapeutic use
Animals
Antioxidants
Antioxidants - metabolism
Antioxidants - therapeutic use
Ascorbic Acid - metabolism
Ascorbic Acid - therapeutic use
Glutathione - metabolism
Glutathione - therapeutic use
Herbicides - metabolism
Herbicides - toxicity
Humans
Iron Chelating Agents - metabolism
Iron Chelating Agents - therapeutic use
Liposomes - therapeutic use
Melatonin - metabolism
Melatonin - therapeutic use
Metallothionein - metabolism
Metallothionein - therapeutic use
NADP - metabolism
Oxidation-Reduction
Oxidative stress
Paraquat
Paraquat - metabolism
Paraquat - toxicity
Rats
Reactive Oxygen Species - metabolism
Vitamin E - metabolism
Vitamin E - therapeutic use
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Summary:Paraquat, a quarternary nitrogen herbicide, is a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The mechanisms of paraquat toxicity involve: the generation of the superoxide anion, which can lead to the formation of more toxic reactive oxygen species, such as hydrogen peroxide and hydroxyl radical; and the oxidation of the cellular NADPH, the major source of reducing equivalents for the intracellular reduction of paraquat, which results in the disruption of important NADPH-requiring biochemical processes. The major cause of death in paraquat poisoning is respiratory failure due to an oxidative insult to the alveolar epithelium with subsequent obliterating fibrosis. Management of paraquat poisoning has remained mostly supportive and has been directed towards the modification of the toxicokinetics of the poison. Currently, there are no true pharmacological antagonists for paraquat and there are no chelating agents capable of binding the poison in the blood or other tissues. Recognizing the fact that paraquat induces its toxic effects via oxidative stress-mediated mechanisms, innovations in the management of paraquat poisoning are directed towards the use of antioxidants. In this review, the status of antioxidants in ameliorating or treating the toxic effects produced by paraquat is presented.
ISSN:0300-483X
1879-3185
DOI:10.1016/S0300-483X(02)00382-7