Role of amifostine in ameliorating the toxicities of anticancer drugs - A preclinical evaluation

Abstract

There are significant toxicities associated with the cancer chemotherapy. The standard regimen for non Hodgkin's lymphoma, the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), is often add- ed with novel drug(s) in research studies to overcome the drug-induced adverse effects on multiple organ sys- tems. The severe pulmonary complications reported in a recent study with one such add-on drug, rituximab raised the interest more towards the exploration of novel cytoprotectants, which is now the key area of research, both in the preclinical and clinical arena. Addition of amifostine, a broad spectrum cytoprotectant to the CHOP regimen is found to be promising against the unwanted toxicities. The present work aimed to study the effect of toxicity in- duced by CHOP chemotherapy in albino rats and histopathologically demonstrate the protection of vital organs by amifostine on CHOP induced toxicities. Eighteen male albino rats were categorized into 3 groups of 6 each – the first one is the control group, the second group received CHOP regimen (for 6 weeks), and the third group re- ceived amifostine and CHOP regimen. The groups were compared for morphological and hematological changes. The histopathological evaluations of the internal organs of all the 3 groups were performed. There was a signifi- cant weight loss in CHOP regimen group, which was lesser in amifostine plus CHOP group. The mean total count was found to be higher in the amifostine plus CHOP group than the CHOP regimen alone group. The histopatho- logical findings in the CHOP regimen group showed sinusoidal congestion in the spleen, tubular necrosis in the kidney, ischemic changes in the heart section were observed; whereas, the amifostine pretreated group showed normal histopathology. The study demonstrated that Amifostine has cytoptrotective effect in CHOP chemothera- py induced toxicity on tissues and organs.