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Toxicity of Diquat and Paraquat

Toxicity of Diquat and Paraquat. Dipyradil Herbicides. Mechanism of Action. Diquat reduced by P450 system to free radical structure Reacts with oxygen and reforms diquat This produces superoxide radical Diquat is again reduced by P450 to restart the cycle

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Toxicity of Diquat and Paraquat

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  1. Toxicity of Diquat and Paraquat Dipyradil Herbicides

  2. Mechanism of Action • Diquat reduced by P450 system to free radical structure • Reacts with oxygen and reforms diquat • This produces superoxide radical • Diquat is again reduced by P450 to restart the cycle • Results in depletion of NADH and production of superoxide radicals

  3. Damage done by Diquat • Depletion of NADH and cyclic metabolism by P450 depletes cellular energy • Free radicals overwhelm cellular buffers • Production of free radicals damage the cellular systems and kill cells

  4. Structure of Diquat

  5. Reduction of Diquat and production of superoxide radical

  6. Hydrogen Peroxide Produced

  7. Clinical Diquat-Paraquat Toxicity • Epithelial damage from caustic effects can lead to extensive tissue damage • Gastrointestinal exposure can lead to oral-esophogeal and gastric erosions and ulcers. • Tissue swelling may result in airway compromise • Fluid influx into damaged GI tube may lead to hypovolemia and renal failure

  8. Internal Tissue Damage • The generation of oxygen radicals leads to tissue damage of highly perfused organs • Lungs, kidneys and CNS may suffer damage • Progressive lung damage may lead to hypoxemia prompting higher oxygen use, worsening the cycle of oxidative lung damage. • Death may be due to shock, diffuse organ failure or hypoxemia.

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