The involvement of Nrf2/HO-1/cytoglobin and Ang-II/NF-κB signals in the cardioprotective mechanism of lansoprazole against cisplatin-induced heart injury

Abstract

Cardiac toxicity is a serious adverse effect of cisplatin (CIS). Lansoprazole (LPZ) is a proton pump inhibitor with promising cardioprotective effects. Our study planned to examine the cardioprotective effect of LPZ against CIS-induced cardiac injury. To achieve this goal, 32 male rats were randomly allocated into four groups. CIS, 7 mg/kg, was injected i.p. on the fifth day of the experiment. LPZ was administered via oral gavage at a dose of 50 mg/kg. The present study revealed that CIS injection induced a remarkable cardiac injury evidenced by an increase in serum ALP, AST, CK-MB, LDH, and troponin-I levels. The cardiac oxidative damage was also observed after CIS injection and mediated by downregulation of GSH, SOD, GST, Nrf2, HO-1, PPAR-γ, and cytoglobin levels associated with the upregulation of MDA content. Besides, CIS injection caused a significant inflammatory reaction mediated by alteration of cardiac NF-κB, STAT-3, p-STAT-3, and IκB expressions. Additionally, cardiac Ang-II expression was significantly increased in CIS control rats, while Ang 1–7 expression was significantly reduced relative to normal rats. In contrast, LPZ administration remarkably ameliorated these changes in the heart of CIS-intoxicated rats. Collectively, LPZ potently attenuated cardiac toxicity induced by CIS via regulation of Nrf2/HO-1, PPAR-γ, cytoglobin, IκB/NF-κB/STAT-3, and Ang-II/Ang 1–7 signals.

Graphical Abstract

Illustrated the possible protective mechanisms of LPZ against CIS-induced cardiotoxicity in rats

Keywords:

• Cisplatin
• cardiotoxicity
• lansoprazole
• Nrf2/HO-1/cytoglobin
• inflammation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.