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.
Keywords: Apoptosis; Inflammation; Lead poisoning; Liver; Oxidative stress; Sinomenine hydrochloride.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.