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

Free Radic Res. 2022 Feb;56(2):209-221. doi: 10.1080/10715762.2022.2067042. Epub 2022 Apr 25.

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: Keap1; Luteolin; Nrf2; cisplatin; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis
  • Cisplatin / adverse effects
  • Heart Diseases* / chemically induced
  • Heart Diseases* / drug therapy
  • Kelch-Like ECH-Associated Protein 1* / metabolism
  • Luteolin* / pharmacology
  • Mice
  • NF-E2-Related Factor 2* / metabolism
  • Oxidative Stress*
  • Signal Transduction

Substances

  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Luteolin
  • Cisplatin