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Pretreatment of CAV Combination Chemotherapy with Tropisetron Shows Less Cardio and Neurotoxicity Side Effects in Rats

Houman Alimoradi, Anita Barzegar-Fallah, Sanaz Mohammadi-Rick, Firouzeh Asadi, Bahram Delfan and Ahmad Reza Dehpour

Tropisetron, a 5-HT3 antagonist receptor, is commonly used for the prevention of emesis following chemotherapy. Lines of evidence point to the anti-inflammatory and immune modulatory properties of tropisetron. The current study aims to investigate whether tropisetron is able to prevent the cardiotoxicity and neurotoxicity induced by doxorubicin (DOX) and vincristine besides its anti emetic effect in a co-administration protocol, since this combination therapy is widely used in various combination chemotherapy regimens. To investigate these effects, intraperitoneal co-administration of doxorubicin and vincristine in CAV combination therapy (Cyclophosphamide, Adriamycin and Vincristine) was used to induce neuro and cardiotoxicity and in treated group tropisetron was injected 1 h prior to combination therapy. General conditions, mortality rate and body weight were measured during the experiment. Moreover, assessment of biomarkers of cardiac injury, ECG (Electrocardiogram) parameters and papillary muscle contractility force were done for evaluating of cardio protective effects of tropisetron. Similarly, hot plate, open field and nerve conduction velocity tests were used for investigation of neuroprotective effects of tropisetron against the side effects of this combination. The findings in the present study indicated that tropisetron pretreatment led to significant decrease in levels of serum cardiac damage biomarkers, electrocardiographic changes and toxicities associated with this combination chemotherapy. Also, it improved behavioral and electrophysiological scores, papillary muscle contractility force and rats’ general conditions. Consequently, it is suggested that tropisetron is beneficial for the prevention of cardiotoxicity and neurotoxicity and could be considered as a new indication for alleviation of side effects of these drugs in combination therapies.