Luteolin attenuated cisplatin-induced cardiac dysfunction and oxidative stress via modulation of Keap1/Nrf2 signaling pathway

Abstract

Cardiovascular complications are a well-documented limitation of cancer chemotherapy. Cisplatin-induced cardiotoxicity threatens the health and life of patients, and limits the application of cisplatin. Oxidative stress is the main mechanism underlying cisplatin-induced cardiac toxicity. Luteolin (Lut) has been reported to possess cardioprotective properties by activating nuclear factor-E2-related factor 2 (Nrf2) -mediated antioxidant response. However, the effect of Lut on cisplatin-induced cardiac damage remains unclear. In this study, we revealed that Lut exerted a protective effect against cisplatin-induced cardiac dysfunction and injury in vivo. In HL-1 cells, Lut was observed to dramatically reduce cisplatin-induced apoptosis and oxidative stress by modulating the Kelch-like epichlorohydrin-associated protein 1 (Keap1)/Nrf2 pathway. Altogether, these findings suggested that Lut showed promise in attenuating cisplatin-induced cardiac injury and might be considered a protective drug candidate for chemotherapy-associated cardiovascular complications.

Keywords:

• Luteolin
• cisplatin
• oxidative stress
• Keap1
• Nrf2

Acknowledgments

We would like to thank Editage (www.editage.cn) for English language editing.

Ethical approval

All the experiments were conducted in compliance with “The Detailed Rules and Regulations of Medical Animal Experiments Administration and Implementation.” The protocols for animal research were approved by the institutional review boards of Zhejiang University School of Medicine, Hangzhou, China.

Author contributions

Q.J. and F.L. initiated and supervised the research. Q.J., F.S., P. D., F.Q., X.W., and M.X. designed and performed the research. F.Q., Y.X., C.Y., and S.Q. helped perform part of assays. Q.J. and F.L. wrote and revised the manuscript. All the authors read and revised the final manuscript.

Disclosure statement

The authors declare that there is no competing financial interest.

Additional information

Funding

Financial support was provided by the Medical Science and Technology Program of Zhejiang Province under Grant (numbers 2021431070 and 2017190933).