Abstract

N-acetylcysteine  (NAC) has largely been used as an effective chemo- protective agent  owing to their beneficial effect in restoring several physiological  parameters and relieving oxidative stress. Interestingly, it has been  suggested that NAC mechanisms of action extend beyond being a precursor  to the antioxidant glutathione and that they may involve several  neurotropic and inflammatory pathways. Exposure to fenitrothion, an  organophosphorus insecticide, promotes oxidative stress and induces  several deleterious changes in the immune response and various tissues  including cerebrum and spleen. The main objective of our study was to  investigate ameliorative efficacy of N-acetylcysteine for  immunological and neurological alterations and oxidative DNA damage  induced by fenitrothion toxicity in cerebrum and spleen tissues of male  rats. Our results revealed that oral exposure to fenitrothion for  30 days caused a reduction in the erythrocyte count in addition to  leukocytosis, lymphocytosis, and neutrophilia. Also, this route of  administration increased the serum levels of LDH, TNF-α, and IL-2 with  reduction in serum immunoglobulins (IgG & IgM) concentrations.  Furthermore, a significant downregulation in the antioxidant markers  (GSH & SOD) with an elevation of free radical (MDA) levels were  noticed. Regarding the brain, fenitrothion administration inhibited AchE  activity and increased brain GABA, serotonin and dopamine levels.  Moreover, it induced an elevation in oxidative DNA damage indicated by  8-hydroxy 2-deoxyguanosine (8OH2dG) and mRNA expression of pro-apoptotic  genes, including Bax, and p53, but Bcl-2 expression was reduced. N-acetylcysteine  co-treatment restored the normal physiological tone in most of these  parameters. Immunostaining for GFAP and Caspase-3 markers in the brain  and spleen tissues were increased respectively. In conclusion, N-acetylcysteine  supplementation has an ameliorative effect against immunotoxic,  neurotoxic and oxidative DNA damage induced by fenitrothion exposure.