Protective effects of sinomenine hydrochloride on lead-induced oxidative stress, inflammation, and apoptosis in mouse liver.

Lead, one of the most common heavy metal toxins, seriously affects the health of humans and animals. Sinomenine hydrochloride (SH) shows antioxidative, anti-inflammatory, antiviral, and anticancer properties. Hence, this study investigated the protective effects of SH against Pb-induced liver injury and explored the underlying mechanisms. First, a mouse model of lead acetate (0.5 g/L lead acetate in water, 8 weeks) was established, and SH (100 mg/kg bw in water, 8 weeks) intervention was administered by gavage. Then, the protective effect of SH against lead-induced liver injury was evaluated through serum biochemical analysis, histopathological analysis, and determination of malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels. The messenger RNA (mRNA) expression levels of the cytokines IL-1β and TNF-α and the apoptosis factors Bax, Bcl-2, and Caspase3 in the liver were detected by quantitative real-time PCR. Then, the expression levels of IL-1β and TNF-α in the liver were detected by ELISA. Immunohistochemical determination of the expression of the apoptosis factors Bax, Bcl-2, and Caspase3 was performed. SH treatment reduced the levels of liver alanine aminotransferase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and MDA in Pb-treated mice, indicating that SH protected the liver from injury and oxidative stress in Pb-treated mice. SH also increased the liver T-AOC of Pb-treated mice. Quantitative real-time PCR, ELISA, and immunohistochemical analysis showed that SH inhibited apoptosis, as indicated by the regulation of the mRNA expression of Bax and Bcl-2 and the reduced expression of Caspase3 and pro-inflammatory factors (IL-1β and TNF-α) in the livers of Pb-treated mice. These results suggest that SH protects the mouse liver from Pb-induced injury. The underlying mechanism involves antioxidative, anti-inflammatory, and anti-apoptotic processes.