MiR-182-5p/TLR4/NF-κB axis contributes to the protective effect of caffeic acid phenethyl ester against cadmium-induced spleen toxicity and associated damage in mice

Abstract

Cadmium (Cd) is a toxic heavy metal pollutant that can be accumulated in organs including the spleen, thereby threatening human health. In this study, the effect of caffeic acid phenethyl ester (CAPE, a bioactive component of honeybee propolis) on CdCl₂-induced spleen toxicity and underlying mechanisms were examined in mice. Histological examinations revealed that CAPE (10 μmol/kg/day b.w.) could mitigate spleen damage induced by CdCl₂ (1.5 mg/kg/day b.w.) in mice. Compared to the mice treated only by CdCl₂, CAPE administration increased the body weight while decreasing the spleen weight, spleen Cd content and spleen to body ratio of the CdCl₂-treated mice. Western blot and ELISA tests revealed that CAPE suppressed CdCl₂-induced inflammation (indicated by the decreases in the levels of inflammatory indictors). TUNEL and Western blot results showed that CAPE suppressed CdCl₂-induced apoptosis through reducing the percentage of TUNEL-positive cells and regulating apoptosis factors. The antagonistic effect of CAPE against CdCl₂-induced spleen toxicity was realized by increasing miR-182-5p expression to regulate the TLR4/NF-κB pathway. Therefore, CAPE could be a food-derived spleen protector to counteract Cd-induced spleen toxicity through alleviating apoptosis and inflammation via the miR-182-5p/TLR4/NF-κB axis.

Keywords: Cadmium; Caffeic acid phenethyl ester; Spleen damage; TLR4; miR-182–5p.