Mulberrin alleviates triclocarban induced hepatic apoptosis and inflammation by regulating the ROS/NF-κB pathway in grass carp

Abstract

Triclocarban (TCC) is commonly used in household, personal care and industrial products and has been frequently detected in different aquatic ecosystems. Mulberrin (Mul) is a key component of the traditional Chinese medicine Romulus Mori with antioxidant and anti-inflammatory properties. The present study aimed to investigate the hepatotoxic effects of TCC in aquatic organisms and explore the protective roles of Mul. Herein, we found that exposure to TCC at environmentally realistic concentrations (5 μg/L) could impair liver function, along with impaired antioxidant defense and infiltration of inflammatory cells. Additionally, we found that TCC increased the ratio of TUNEL staining positive cells, accompanied by upregulation of pro-apoptotic protein (Bax, caspase3 and caspase9), and downregulation of anti-apoptotic proteins (Bcl2). In contrast, Mul supplementation reversed the hepatic pathological damage, ROS elevation, and apoptosis induced by TCC, likely due to hyperactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Additionally, Mul supplementation suppressed the mRNA levels of proinflammatory factors (TNF-α, IL-1β, IFN-γ, IL-6 and IL-8) and enhanced the mRNA levels of anti-inflammatory factors (TGFβ1, TGFβ2, IL4, IL10 and IL11) in the liver of carp. We also discovered that Mul supplementation suppressed TCC-induced nuclear nuclear factor κB (NF-κB) elevation. In conclusion, Mul enhances Nrf2 signaling cascades and counteracts the NF-κB inflammatory program to rescue hepatotoxicity induced by TCC, providing new insights into the hepatotoxic effects of TCC and potential protection strategies for heart injury induced by TCC.

Keywords: Hepatic pathological damage; Mulberrin (Mul); Nuclear factor erythroid 2-related factor 2 (Nrf2); Nuclear factor κB (NF-κB); Triclocarban (TCC).