Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine.

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 +/- 0.18 vs 2.91 +/- 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 +/- 24.36 vs 749.16 +/- 102.61 U/gHb; P < 0.05), catalase activity (1.86 +/- 0.18 vs 2.43 +/- 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 +/- 0.21 vs 2.28 +/- 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 +/- 0.51 vs 8.00 +/- 0.12 -log(2); P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 +/- 1.04 vs 70.8 +/- 1.09%; P < 0.05) and macrophage migration inhibition (20.38 +/- 0.99 vs 67.16 +/- 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-small u, Cyrillic levels (40.7 +/- 3.21 vs 55.84 +/- 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-alpha level (64.19 +/- 6.0 vs 23.16 +/- 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.