Abstract
Excessive subchronic fluoride exposure can cause severe damage to detoxification organs, including the liver. Sodium butyrate has anti-inflammatory, antitumor, antioxidant and immunomodulatory properties. However, relatively few studies have investigated the effects of sodium butyrate on liver injury caused by subchronic fluoride exposure. The purpose of this research was to investigate the effect and mechanism of sodium butyrate on fluoride-induced hepatic inflammatory injury via the expression of nod-like receptor protein 3 (NLRP3). Mice were subjected to randomization into four groups, each comprised of ten animals, and all groups received oral gavage treatment for 8 weeks. Following the treatment regimen, liver tissue specimens were collected for analysis. The levels of inflammatory factors and NLRP3 and its downstream proteins were measured to evaluate the therapeutic effect of sodium butyrate. The results of histological hematoxylin and eosin (H&E) staining showed that the hepatocytes in the subchronic fluoride-exposed group were loosely arranged, with obvious fatty vacuolar degeneration and inflammatory cell infiltration, suggesting chronic inflammation. The gaps and arrangement of liver cells in the treatment group were similar to those in the control group, with less vacuolar degeneration and inflammatory infiltration. The results of the biochemical assay showed that the transaminase content in the liver tissue of the mice in the subchronic fluoride-exposed group increased, suggesting liver injury. In addition, the detection of oxidative stress indicators showed that chronic subchronic fluoride exposure could lead to an increase in the level of oxidative stress in the liver, and the treatment alleviated this increase. RT-qPCR results showed that compared with those in the control group, the mRNA levels of the inflammatory factors TNF-α, IL-6 and IL-1β, the NLRP3 inflammasome and its downstream factors NLRP3, caspase-1, gasdermin D (GSDMD) and IL-18 increased in the liver tissue of mice in the subchronic fluoride-exposed group. Treatment alleviated these changes, which proved that sodium butyrate released inflammatory factors during chronic subchronic fluoride exposure and inhibited the protein expression of activated NLRP3 to a certain extent. This result shows that sodium butyrate can play a protective role by antagonizing the production of activated inflammasomes and their downstream inflammatory factors in the livers of subchronic fluoride-exposed mice.