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

Abstract

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-γ 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-α 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.

N-acetylcysteine Offers Cardioprotection by Decreasing Cardiac Lipid Hydroperoxides and 8-Isoprostane Level in Isoproterenol-Induced Cardiotoxicity in Rats

“…These results suggest that NAC possess significant antioxidant activity. This is in line with previous literature stating the antioxidant properties of NAC [41,42]. NAC has been demonstrated to inhibit oxidative stress and DNA damage.…”

Assessment of phosphamidon‐induced apoptosis in human peripheral blood mononuclear cells: Protective effects of N‐acetylcysteine and curcumin

“…• C in CO 2 incubator (MCO-15AC, Sanyo, Japan) together with increasing concentrations of phosphamidon (0-20 μM) for different time periods (6,12, and 24 h). The dose of phosphamidon that we have selected in this study is based on earlier reports that phosphamidon like other organophosphates induces apoptosis/necrosis at concentrations ranging from 0 to 100 μM in SH-SY5Y human neuroblastoma cells [12].…”

Polyphenol-rich fraction of Parquetina nigrescens mitigates dichlorvos-induced neurotoxicity and apoptosis

“…However, groups treated with prf of P. nigrescens showed significantly lower levels of H 2 O 2 generation and MDA formed which is suggestive of its antioxidant capacity in both the cerebellum and cerebrum. Various reports have shown the amelioration of dichlorvos-induced neurotoxicity by agents with antioxidant activities [1], [28].…”