Early Dose-Related Cardiorenal Effects of Cisplatin: Integrated Biochemical, Molecular and Histopathological Evaluation in an Experimental Rat Model
Gülsüm Abuşoğlu, Melek Altunkaya, Mehmet Burak Ateş, Ayşegül Bulut, Bahadır ÖztürkBackground/Objectives: Cisplatin (CP) is a widely used chemotherapeutic agent; however, its dose-dependent effects on different tissues are not fully understood. This study aimed to investigate the early dose-related cardiorenal toxicity of CP at biochemical, molecular, and histopathological levels. Methods: Male Wistar albino rats were divided into four groups: Control, 5 mg/kg CP, 7.5 mg/kg CP, and 12 mg/kg CP. Cardiac and renal tissues were collected three days after administration. Oxidative stress and inflammatory parameters were analyzed using ELISA. Histopathological evaluation and semi-quantitative scoring were performed on tissue sections. Apoptosis-related proteins were assessed using Western blotting and immunohistochemistry. Results: In both renal and cardiac tissues, LPO, MDA, and SOD levels showed significant dose-dependent changes, whereas inflammatory parameters did not differ significantly among the groups. Although Bax and Bcl-2 proteins displayed significant dose-dependent variations in both tissues at the protein level, immunohistochemical analyses showed no notable differences in cardiac tissue. Conclusions: Acute cisplatin exposure produced dose-related biochemical, molecular, and histopathological alterations in both cardiac and renal tissues. Oxidative stress-related changes were more prominent than cytokine-mediated inflammatory responses during the acute experimental period. Within the conditions of this acute model, lower cisplatin doses were associated with less pronounced tissue alterations.