Nicotinic acid attenuates experimental non-alcoholic steatohepatitis by inhibiting the NLRP3 inflammasome/pyroptosis pathway

• Published in: Biochemical pharmacology 2023-10, Vol.216, p.115762-115762, Article 115762
• Main Authors: Cardoso-Lezama, Irina, Fuentes-Figueroa, Miguel Á., Ramos-Tovar, Erika, Márquez-Quiroga, Linda V., Ortiz-Fernández, Arturo, Vargas-Pozada, Eduardo E., Arellanes-Robledo, Jaime, Tsutsumi, Víctor, Muriel, Pablo
• Format: Article
• Language: English
• Subjects: Cirrhosis; Liver disease; Nicotinic acid; Non-alcoholic steatohepatitis
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2023.115762

[Display omitted] Non-alcoholic steatohepatitis (NASH) is a global public health concern that may progress into fibrosis, cirrhosis, and liver cancer, with limited curative treatment options. While the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is closely linked to NASH progression, nicotinic acid (NA), a vitamin used for the treatment of dyslipidemia, is an emerging pharmaceutical treatment for hepatic steatosis and fibrosis. Here, we investigated pharmacological effects of NA on experimental NASH and whether NLRP3 inflammasome/pyroptosis inhibition is an associated mechanism of action. Rats were fed a high-fat sucrose diet supplemented with cholesterol and a low dose of CCl4. NA significantly reduced inflammation by decreasing the protein levels of tumor necrosis factor-alpha and nuclear factor kappa B. Moreover, NA inhibited the formation of NLRP3- apoptosis-associated speck-like protein containing caspase recruitment domain-Caspase-1, decreasing interleukin-1beta, interleukin-18, and gasdermin D protein. In addition, NA reduced tumor growth factor-beta, alpha-smooth muscle actin, and hepatic levels of collagen-1, consequently decreasing extracellular matrix synthesis. Our results indicate that NA can inhibit NASH progression and encourage further basic and clinical studies on the use of NA for the treatment of human NASH.