Hesperidin attenuates cisplatin-induced cardiotoxicity in rats through regulating autophagy

Heidari Kahkesh, Hoori; Amini, Negin; Badavi, Mohammad; Dianat, Mahin; Nejaddehbashi, Fereshteh; Hoseinynejad, Khojasteh

doi:10.22038/ajp.2026.27360

Hesperidin attenuates cisplatin-induced cardiotoxicity in rats through regulating autophagy

Articles in Press

Document Type : Original Research Article

Authors

¹ 1Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2The Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, School of Medicine, Ahvaz Jundishapur

² Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

10.22038/ajp.2026.27360

Abstract

Objective: Cisplatin is a well-known anticancer drug whose use has been limited due to a variety of side effects. Evidence has confirmed that cisplatin consumption is associated with cardiac toxicity. Unfortunately, no drug has yet been found to treat cardiac toxicity or reduce the side effects caused by cisplatin. However, hesperidin has been identified as an antioxidant agent which has protective effects on the heart tissue. This study explored the impact of hesperidin on cisplatin-induced cardiac toxicity through its antioxidant effect and adjustment of autophagy.
Materials and Methods: It included male Wistar rats allocated into five groups: sham, cisplatin: animals treated with cisplatin (7.5 mg/kg, intraperitoneally) on the 4^th day; and four groups which received hesperidin (50, 100, and 200 mg/kg, gavage, 1 week) along with cisplatin on the 4^th day. A mixture of ketamine and xylazine was used to anesthetize all animals on day 8 to obtain blood and tissue samples and to record ECG.
Results: The findings indicated that cisplatin led to an increase in creatine kinase-MB, lactate dehydrogenase, and malondialdehyde levels, and a reduction in total antioxidant capacity in heart tissue. Moreover, it reduced the expression of microtubule‑associated protein light chain (LC3-II) and beclin-1. ECG parameters included: Heart rate (HR) and QRS voltage complex which were reduced by cisplatin. However, hesperidin (100, and 200 mg/kg) reversed these changes.
Conclusion: Hesperidin could protect cardiac tissue against cisplatin administration by exerting its antioxidant effect and regulating autophagy in a dose-dependent manner.

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