Caffeic acid phenethyl ester mitigates cadmium-induced hepatotoxicity in mice: Role of miR-182-5p/TLR4 axis

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 CdCl 2 (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 CdCl 2 -induced oxidative stress via PI3K/Akt/mTOR pathway and inhibited apoptosis by regulating apoptosis markers. CAPE also suppressed the CdCl 2 -induced inflammation by reducing the inflammatory mediators, including TNF-α, IL-6 and IL-1β. Furthermore, CAPE alleviated CdCl 2 -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 CdCl 2 -induced hepatotoxicity, and may provide novel insights into the treatment of cadmium-related diseases.