Combined ameliorative effect of N-Acetylcysteine and Vitamin C on Cyclophosphamide-Induced Immunosuppression in Balb/C mice via Immunomodulatory, anti-oxidant and downregulation of pro-inflammatory markers

Abstract

Background: The present study investigated immunomodulatory effects of N -Acetylcysteine and Vitamin C on Cyclophosphamide induced Immunosuppression in Balb/C mouse models. Methods: Thirty two Balb/c mice randomly divided into 4 groups. One group of healthy mice acted as normal control. 80 mg/kg/day cyclophosphamide (i.p.) was administered on day 1-3 and 9 for all other groups. From day 4 to 21, the cyclophosphamide treated mice were administered as: saline in positive control, N- Acetylcysteine (200mg/kg), N-Acetylcysteine (200mg/kg) + Vitamin C (200mg/kg). On 22^nd day, thymus and spleen tissues isolated, processed for histopathological examination. Blood samples were analyzed for hematological, biochemical, immunological and parameters. Results: NAC and Vit C prevented the Cyclophosphamide induced spleen and thymus injury compared with normal control, prevented the decrease in numbers of peripheral RBC, WBC, Hb and platelets, providing supportive evidence for their anti-leukopenia activities; reversed decreased activities of catalase (CAT), glutathione (GSH), GR and rise in MDA. NAC and Vit C also enhanced humoral immune function through increasing level of IgG; significantly decreasing the proinflammatory cytokines-TNF-α and IL-2 levels in serum; produced an increase in circulating serum immunoglobulins in haemagglutinating antibody titre test. Decrease in foot pad edema in delayed-type hypersensitivity reaction test; showed an increase in the neutrophil adhesion to the nylon fibres. Conclusion: Taken together, our results provide scientific evidence for synergic effect between NAC and Vit C as a co-treatment for enhancing humoral and cellular immune functions, augmenting antioxidant, anti-inflammatory and immunomodulatory effects.