The simultaneous effect of Hydroxychloroquine and Pentoxifylline on the doxorubicin-induced cardiotoxicity in the rat animal model

Abstract

Introduction: Doxorubicin (DOX) is antineoplastic drug which is used for treatment of various solid and non-solid neoplasms but its use is limited due to its side effects affecting heart. Hydroxychloroquine (HCQ) can inhibit apoptosis of cardiomyocytes and reduce cardiomyopathy and heart failure. Also Pentoxifylline (PTX) ) has an anti-inflammatory and antioxidant effect. Purpose: The effects of simultaneous usage of PTX and HCQ on cardiactoxicity of DOX in rat models will be evaluated in this paper. Materials and Methods: Wistar male rats were divided to 5 groups of control, DOX, DOX with HCQ, DOX with PTX, and DOX with the combination of the two drugs. The first group received saline via I.P injection. The second group received DOX (2mg/kg/48h(I.P)) in 2 weeks. The third group received HCQ with 5mg/kg dosage in conjunction with DOX, and the fourth group received PTX (I.P) with 50mg/kg dosage in conjunction with DOX. The last group received the combination of two HCQ and PTX drugs in conjunction with DOX. After evaluating the studied groups in terms of cardiac hemodynamic parameters, histological studies were performed on the heart tissue. Findings: The simultaneous administration of DOX with PTX and HCQ improved the hemodynamic parameters such as MAP, SAP and KVdP/dt and heart weight compared to the DOX group, and in histopathological studies, the complications caused by DOX were partially compensated. Conclusion: In this study, it was observed that the simultaneous use of DOX with HCQ and PTX can significantly reduce the cardiotoxicity caused by DOX by affecting the hemodynamic parameters.