There are many synthetic and natural chemotherapeutic agents available for the treatment of cancer but none of them is effective alone. Some of the most widely used chemotherapeutic agents are doxorubicin, cisplantin, methotrexate, mitomycine and cyclophosphamide. Cyclophosphamide (CP) remains the most widely used alkylating agent used in cancer chemotherapy and still extensively studied both clinically and experimentally. Because of its widespread use side effects with CP treatment are frequently reported. The immunosuppressive effects of CP are the major cause of concern for oncologists.

          It is believed that used of immunomodulating herbs and/ or antioxidants may provide great relief from the side effects of CP in the patients. The present study was undertaken to assess potential of some antioxidant agents in the form of herbal extracts and purified antioxidant compounds in abrogating toxicity of CP in mice. In this study, three herbal extracts viz; Emblica officinalis, Juglans regia and Ginkgo biloba and two well-known antioxidants viz; vitamin C and catechin have been used.

          All the plant extracts alone and in combination with CP-treated animals showed improvement in the cellularity of lymphoid organs. Plant extracts treatment caused a significant improvement in humoral immunity, cell mediated immunity and non-specific immune functions in CP-treated animals. Animals treated with vitamin C (10 mg/kg body weight) showed no improvement in the relative organ weights. Vitamin C and catechin along with CP restored the specific and non-specific immune response.

          J. regia extract showed appreciable tumor inhibitory activity in Ehrlich ascites tumor challenged animals. It also showed an increase in percentage survival time and showed reduction in the mean body weight of tumor bearing mice.

          A significant reduction was observed in cytochrome P450 content in liver and kidney of E. officinalis and in kidney of J. regia treated animals where as no change was observed in G. bioloba treated animals. Ginkgo and J, regia extract along with CP resulted in a significant improvement in the Cyt. P450 content in both the tissues. Extracts of E. officinalis and J. regia did not show induction in the glutathione S-transferase (GST) activtiy except G. biloba. All the three plants showed restoration in the activities of GST in CP-treated animals in both the tissues. J. regia and G. biloba extracts significantly induced reduced glutathione (GSH) levels in both the tissues (liver and kidney) whereas induction by E. officinalis was not significant. These plants also restored the depleted level of GSH in CP treated animals. Almost all the plant extracts showed significant augmentation in the activities of antioxidant enzymes in both the tissues especially in CP intoxicated mice.

          Vitamin C alone failed to stimulate the drug metabolizing enzymes effectively in kidney but in combination with CP showed an improvement in the cytochrome P450 content in both the tissues. Vitamin C did not induce GST and GPx in control animals but it restored the depleted levels of GST, glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in CP treated animals. Catechin + CP treatment showed a significant improvement in the content of Cyt. P450 in liver and kidney as compared to CP treated animals. Catechin and catechin + CP groups showed a significant induction in the activity of CAT, SOD, GPx, GST and in the level of GSH in liver and kidney except glutathione peroxidase in the kidney.

          CP-treated animals that were administered plant extracts and antioxidant compounds showed a decreased LPO level in kidney and liver as compared to CP-treated animals.

          Large number of natural antioxidants and herbal preparations are available to scavenge the reactive oxygen species and modulate the immune system. It is the need of hour to conduct detailed studies on selected natural antioxidant compounds that have potential to modulate the immune system as well as suppress the toxicity of the synthetic drugs used for the treatment of cancer. Immunomodulatory therapy could provide an alternative to conventional chemotherapy for the varieties of advantage its offers. The present study conducted on mice offers some weightage to those advantages.