Citronellal alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis via Na+ /H+ exchanger-1 inhibition.

The medical usage of Doxorubicin (DOX) as a chemotherapeutic agent is restricted owing to its cardiotoxic properties. This study was designed to explore the effect and underlying mechanisms of Citronellal (CT) on DOX-related cardiotoxicity in rats. Rats were divided into six groups: control, DOX, CT, Lithium chloride (LiCl) (a Na+/H+exchanger-1 [NHE1] activator), DOX + CT, and DOX + CT + LiCl. To induce cardiotoxicity, a cumulative dose of 15 mg/kg DOX was intraperitoneally injected into rats. CT (150 mg/kg) and LiCl (1 mg/kg) were given daily by oral gavage for 6 weeks. CT improved cardiac functional parameters and attenuated the cardiac pathological changes induced by DOX. Further study indicated that CT administration regulated the levels of oxidative stress and apoptosis-related factors and in myocardial tissues, reducing cell per-oxidative damage and apoptosis. Besides this, CT attenuated DOX-induced NHE1 upregulation, and the preventive effects of CT against DOX-induced cardiotoxicity were abrogated by the concurrent administration of LiCl. These results demonstrate that CT could ameliorate DOX-induced cardiotoxicity by inhibiting the NHE1-mediated oxidative stress, apoptosis in rats. © 2021 Wiley Periodicals LLC.

Citation

Xu Liu, Yue Qiu, Ning Huang, Yan-Hua Liu, Huan-Huan Wang, Ya-Nan Yu, Yu-Ting Song, Guang-Rui Wan, Shuang-Xi Wang, Peng Li, Ya-Ling Yin. Citronellal alleviates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis via Na+ /H+ exchanger-1 inhibition. Journal of biochemical and molecular toxicology. 2022 Mar;36(3):e22971

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PMID: 34813134

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