Mechanism of Cadmium Exposure Induced Hepatotoxicity in the Mud Crab (Scylla paramamosain): Activation of Oxidative Stress and Nrf2 Signaling Pathway

Cadmium, one of the most toxic heavy metals, can cause severe oxidative damage to aquatic animals. However, the mechanism whereby the mud crabs respond to cadmium exposure remains unclear. This study investigated the effects of cadmium exposure on oxidative stress and histopathology changes and evaluated the role of the Nrf2 signaling pathway in regulating responses to cadmium-induced hepatotoxicity were investigated in mud crabs. Mud crabs were exposed to 0, 0.01, 0.05, and 0.125 mg/L cadmium for 21 d. The present results indicated that cadmium exposure increased hydrogen peroxide (H2O2) production, lipid peroxidation and tissue damage, but decreased the activity of superoxide dismutase (SOD) and catalase (CAT), and caused lipid peroxidation and tissue damage. The results of an integrated biomarker index analysis suggested that the toxicity of cadmium was positively related to cadmium concentration. The expression levels of the Nrf2 signaling pathway (Nrf2, metallothionein, and cytochrome P450 enzymes) were up-regulated after cadmium exposure. Silencing of Nrf2 in vivo decreased antioxidant gene (SOD, CAT, and glutathione S-transferase) expression, suggesting that Nrf2 can regulate antioxidant genes. Knocking down Nrf2 in vivo also significantly decreased the activity of SOD and CAT after cadmium exposure. Moreover, silencing of Nrf2 in vivo enhanced H2O2 production and the mortality rates of mud crabs after cadmium exposure. The present study indicated that cadmium exposure induced hepatotoxicity in the mud crab by increasing H2O2 content, which decreased the antioxidant capacity, leading to cell injury. In addition, the Nrf2 is activated to bound with antioxidant response element, initiating the expression of antioxidant enzyme genes during cadmium induced hepatotoxicity in the mud crabs.

Automated summary

This study revealed that cadmium exposure induced oxidative stress and tissue damage in mud crabs, with the Nrf2 signaling pathway playing a crucial role in regulating responses to cadmium-induced hepatotoxicity.