Ultrastructural Changes and Inflammatory Processes of Day-Dependent Cisplatin Administration on Rat Cardiac Tissue

Abstract

Aim: Cisplatin (CP) is used to treat a variety of cancers as a chemotherapeutic agent. This drug has also severe side effects and its use exhibits serious toxicity in a number of organs, including kidney and heart. The aim of the present study was to evaluate the ultrastructural and inflammatory changes induced by CP treatment in rat cardiac tissue in a time-dependent manner. Material and Methods: Rats were randomly divided into three experimental groups; control (only saline), CP D2 (treated with CP 2.5 mg/kg/day for 2 days), and CP D7 (treated with CP 2.5 mg/kg/day for 7 days). Cardiac tissues were examined under an electron microscope. Inflammation markers including tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were analyzed by immunohistochemistry. In addition, electrocardiography was performed to measure the electrical activity. Results: The ultrastructural analysis of the CP D7 group revealed that myofibrils were disrupted and disorganized, mitochondria degenerated, and interstitial edema developed. When compared to the control and CP D2 groups, there was a noticeable increase in the level of TNF-α and IL-1β expression in the CP D7 group according to immunohistochemistry results. Electrocardiography showed that RR interval was longer in CP D7 than CP D2 and control groups. Conclusion: CP for 7 days damaged the ultrastructural morphology in cardiac tissue. Therefore, these findings suggest that the potential therapeutic approaches to reduce mitochondrial damage and inflammation against toxicity caused by CP may provide for clinically significant prevention when using the drug for an extended period of time.