Cadmium (Cd) is known as a highly toxic heavy metal and has been reported to induce hepatotoxicity in animals. Nano-selenium (NSe) is an antioxidant that plays many biological roles such as oxidative stress alleviation. The purpose of this study is to explore the mechanism of action by which NSe inhibits Cd-induced hepatic toxicity and oxidative stress. Sixty eight-week-old male Kunming mice were randomly divided into four groups (15 mice per group). The control group and cadmium groups received distilled water, whereas the sodium-selenite group received 0.2 mg/kg SSe and the NSe group received 0.2 mg/kg NSe intragastrically for 2 weeks. On the last day, all the other groups were treated with Cd (126 mg/kg) except for the control group. The results obtained in this study showed that NSe alleviated Cd-induced hepatic pathological changes. Furthermore, NSe reduced the activities of ALT and AST as well as the content of MDA, while elevated the activities of T-AOC, T-SOD and GSH (P < 0.05). In addition, the NSe group significantly increased mRNA expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO-1, GST, GSH-Px, CAT and SOD) compared to the Cd group (P < 0.05). In conclusion, NSe shows its potentiality to reduce Cd-induced liver injury by inhibiting oxidative stress and activating the Nrf2 pathway.

Lipopolysaccharide (LPS) is an endotoxin that can cause an imbalance between the oxidation and antioxidant defense systems and then induces hepatic damages. Ferulic acid (FA) has multiple biological functions including antibacterial and antioxidant activities; however, the effect of FA on lipopolysaccharide-induced hepatic injury remains unknown. The purpose of this study was to investigate the mechanism of action of dietary Ferulic acid against Lipopolysaccharide-induced hepatic injuries in Tianfu broiler chickens. The results showed that supplementation of FA in daily feed increased body weight (BW) and decreased the feed conversion ratio (FCR) in LPS treatment broilers significantly (p < 0.05). Additionally, supplement of FA alleviated histological changes and apoptosis of hepatocytes in LPS treatment broilers. Supplement of FA significantly decreases the activities of ROS. Interestingly, the levels of antioxidant parameters including total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and glutathione (GSH) in LPS group were significantly increased by the FA supplementation (p < 0.05). Nevertheless, administration of LPS to broilers decreased the expressions of Nrf2, NQO1, SOD, GSH-Px, CAT and Bcl-2, whereas it increased the expressions of Bax and Caspase-3 (p < 0.05). Moreover, the expressions of Nrf2, NQO1, SOD, CAT, Bcl-2 were significantly upregulated and Caspase-3 were significantly downregulated in the FL group when compared to LPS group (p < 0.05). In conclusion, supplementation of FA in daily feed improves growth performance and alleviates LPS-induced oxidative stress, histopathologic changes, and apoptosis of hepatocytes in Tianfu broilers.

Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-induced hepatotoxicity in Tianfu broilers. According to the results, AA-I-induced hepatotoxicity in Tianfu broilers was evidenced by the elevation of liver weight, levels of serum glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). Furthermore, hepatocyte swelling, vesicular degeneration and steatosis were observed. Additionally, AA-I elevated the production of reactive oxygen species (ROS) and induced oxidative stress, which further led to excessive apoptosis, characterized by mitochondrial depolarization, upregulation of Bax, and down-regulation of Bcl-2 expression. In conclusion, the mechanism of AA-I-induced hepatotoxicity was associated with oxidative-stress-mediated apoptosis and mitochondrial damage.