*Article* **Ameliorative Effects of Oyster Protein Hydrolysates on Cadmium-Induced Hepatic Injury in Mice**

**Jingwen Wang 1,2,3,4,†, Zhijia Fang 1,2,3,4,\*,†, Yongbin Li 1,2,3,4, Lijun Sun 1,2,3,4, Ying Liu 1,2,3,4, Qi Deng 1,2,3,4 and Saiyi Zhong 1,2,3,4,\***


**Abstract:** Cadmium (Cd) is a widespread environmental toxicant that can cause severe hepatic injury. Oyster protein hydrolysates (OPs) have potential effects on preventing liver disease. In this study, thirty mice were randomly divided into five groups: the control, Cd, Cd + ethylenediaminetetraacetic acid (EDTA, 100 mg/kg), and low/high dose of OPs-treatment groups (100 mg/kg or 300 mg/kg). After continuous administration for 7 days, the ameliorative effect of OPs on Cd-induced acute hepatic injury in Cd-exposed mice was assessed. The results showed that OPs significantly improved the liver function profiles (serum ALT, AST, LDH, and ALP) in Cd-exposed mice. Histopathological analysis showed that OPs decreased apoptotic bodies, hemorrhage, lymphocyte accumulation, and inflammatory cell infiltration around central veins. OPs significantly retained the activities of SOD, CAT, and GSH-Px, and decreased the elevated hepatic MDA content in Cd-exposed mice. In addition, OPs exhibited a reductive effect on the inflammatory responses (IL-1β, IL-6, and TNF-α) and inhibitory effects on the expression of inflammation-related proteins (MIP-2 and COX-2) and the ERK/NF-κB signaling pathway. OPs suppressed the development of hepatocyte apoptosis (Bax, caspase-3, and Blc-2) and the activation of the PI3K/AKT signaling pathway in Cd-exposed mice. In conclusion, OPs ameliorated the Cd-induced hepatic injury by inhibiting oxidative damage and inflammatory responses, as well as the development of hepatocyte apoptosis via regulating the ERK/NF-κB and PI3K/AKT-related signaling pathways.

**Keywords:** cadmium; oyster protein hydrolysate; hepatic injury; oxidative stress; inflammatory response; hepatocyte apoptosis
