Caffeic acid phenethyl ester mitigates cadmium-induced hepatotoxicity in mice: Role of miR-182-5p/TLR4 axis
Rili Hao, Junlin Ge, Yong-Feng Ren, Xinyu Song, Yang Jiang, Dongxiao Sun‐Waterhouse, Feng Li, Dapeng Li
Abstract
Cadmium (Cd), an environmental pollutant, is evidenced to cause hepatotoxicity. In this study, the potential protective effect of caffeic acid phenethyl ester (CAPE) on cadmium-induced liver damage was investigated. Forty male mice were treated daily with either CdCl2 (1.5 mg/kg body weight (b.w.), gavage) or CAPE (10 μmol/kg b.w., gavage) or both for 4 weeks. CAPE administration significantly reduced Cd level and liver and body weight, and increased AST, ALT and ALP level. Moreover, CAPE prevented CdCl2-induced oxidative stress via PI3K/Akt/mTOR pathway and inhibited apoptosis by regulating apoptosis markers. CAPE also suppressed the CdCl2-induced inflammation by reducing the inflammatory mediators, including TNF-α, IL-6 and IL-1β. Furthermore, CAPE alleviated CdCl2-induced reduction of TLR4. It should be noted that this effect was achieved by targeting miR-182-5p, and CAPE improved miR-182-5p level. The improvement of the liver tissue histopathology by CAPE confirmed the biochemical data. These results show for the first time that miR-182-5p/TLR4 axis involved in CAPE's protection against CdCl2-induced hepatotoxicity, and may provide novel insights into the treatment of cadmium-related diseases.