In an attempt to further clarify the mechanisms of paraquat lung injury, paraquat toxicity was studied in selenium (Se)-deficient rats. Chronic respiratory disease-free rats fed a basal Se-deficient diet or a basal diet supplemented with 0.5 or 2.0 ppm of Se for 40 days after weaning were injected with 25 mg/kg of paraquat dichloride (ip). Within 4 hr after paraquat injection, 50% of the rats fed the Sedeficient regimen died, exhibiting neurological and respiratory signs of distress prior to death, whereas all rats fed Se-supplemented diets survived for this short time span. Excised lungs from surviving Se-deficient rats injected with paraquat showed extensive lung damage, as evidenced by gross examination, increased lung weights, and increases in cystosolic lung lysosomal enzymes, and exhibited a significant increase of thiobarbituric acid (TBA)-reactive products. Excised lungs from Se-supplemented rats failed to show similar increases in these indices of paraquat-induced lung injury. Our data confirms and extends previous findings of others that paraquat toxicity is enhanced in Se-deficient animals and suggests that lipid peroxide formations may play a role in the enhanced susceptibility.
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