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Abstract SUMMARY AND CONCLUSION SUMMARY AND CONCLUSION Anticancer drugs are well known immunotoxic agents. To assess the effects of these drugs on the immune system: Immunofunctional assays using rats are needed for the drugs assumed to be immunotoxic at a dose level which is not overtly toxic. The immunofunctional test used in our study is the plaque forming cell (PFC) assay which is the most popular assay to assess the humoral function. In our study: different doses of both single and 7 days administration were used to study the immunotoxic, cytotoxics haematotoxic and systemic toxic effects of two of the a1kylating agents which are: cyclophosphamide which has well known immunosuppressive effective and melphalan which widely used with chemotherapy and compare between the toxic effects of both drugs. The study included 120 adult albino rats that divided into 4 groups, each group divided into 3 subgroups: Group I: Included 30 animals treated as follow: • 10 rats were injected with Cy. at dose of 10 mg/kg LV. (single). • 10 rats were injected with Cy. at dose of30 mg/kg LV. (single). • 10 rats were injected with saline IV. (single) i.e, control group. Group II: Included 30 animals treated as follows: • 10 rats were treated with melphalan at dose 6 mg/kg oral (single). • 10 rats were treated with melphalan at dose 20 mg/kg oral (single). • 10 rats were treated with 1% carboxymethyl cellulose oral (single) i.e., control group. SUMMARY AND CONCLUSION Group III: Included 30 animals treated as follows: • Ten animals were injected daily for 7 days with cyclophosphamide at dose 3 mg/kg 1.V. • Ten animals were injected daily for 7 days with cyclophosphamide at dose 10 mg/kg 1.V. • Ten animals were injection daily for 7 days with saline LV. (control). Group IV: Included 30 animals treated as follows: • Ten animals were treated daily for 7 days with melphalan at dose (2 mg/kg) oral. • Ten animals were treated daily for 7 days with melphalan at dose (6 mg/kg) oral. • Ten animals were treated daily for 7 days with I% carboxymethyl cellulose oral (control). Each rat subjected to: • Rough estimation of systemic toxicity by body weight gain, • Cytotoxicity of the drug by quantitating the number of spleen cells per 106 spleen cells. • Immunotoxicity of the drugs by assessing the humoral immunity using the plaque forming cell (PFC) assay to determine PFC response per 106 cells. • Haematotoxic effect of the drugs by estimation ofW.B.Cs. count (total and differential) and platelet count. I I SUMMARY AND CONCLUSION Our results showed that: Witlr single administration: Cyclophosphamide suppressed PFC at dose lower than that causing decrease in body weight gain, spleen weight and spleen cellularity while in melphalan: body weight gain, spleen weight and cellularity tended to decreased at dose lower than that causing reduction of PFC response also leukopenia and thrombocytopenia was dose related which was more with melphalan than Cy. Comparison of the toxic effects of both drugs resulted into: the melphalan caused more toxic effects (in all the measured parameters) than cyclophosphamide especially the single high dose while the toxic effects of both drugs nearly equal in the single low dose. Witi, 7 days administration: The spleen weight, spleen cellularity and PFC response tended to decrease at the same dose with (Cy.) while body weight gain, spleen weight and cellularity tended to decreased at dose lower than that causing reduction ofPFC with melphalan. Leukopenia and thrombocytopenia was dose related comparison of the toxic effects indicated that melphalan induced more toxic effects (in all the measured parameters) than cyclophosphamide especially the multiple high dose while there is nearly equal toxic effects with the low daily dose. from tire results of this study we concluded tlrat: • Although PFC assay is well known old method but considered highly sensitive indicator for humoral immunity assessment. • Although, the melphalan is widely used in therapeutics, its toxic effects especially on the immune system have to be more studied, our SUMMARY AND CONCLUSION work showed that melphalan especially in high doses is more immunotoxic, cycotoxic and haemotoxic in comparison to Cy. Recommendation: • In case of ovarian carcinoma we recommended using Cy. Because melphalan is more immunotoxic, cytotoxic and hematotoxic effects. • The repeated daily doses has to be recommended because the single high dose is more immunotoxic, cytotoxic and hematotoxic than the repeated daily doses. • Immunofunctional assays and C.B.C. has to be recommended in patients receiving Cy. Or melphalan. |