Pentadecanoic acid attenuates thioacetamide-induced liver fibrosis by modulating oxidative stress, inflammation, and ferroptosis pathways in rat.

Pentadecanoic acid (PDA) has been reported as a histone deacetylase 6 inhibitor. Numerous studies have shown that Histone deacetylases (HDACs) are significantly involved in the development of fibrosis. The present study focused on assessing the anti-fibrotic properties of PDA in ameliorating hepatic fibrosis induced by thioacetamide (TAA) in Wistar rats. PDA was administered orally at the doses of 10, 20 and 40 mg/kg daily, whereas TAA was administered intraperitoneally at a dose of 200 mg/kg twice weekly, for a period of 9 weeks. Administration of TAA significantly increased the relative and absolute liver weight, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), myeloperoxidase (MPO), malondialdehyde (MDA) and reduced the glutathione (GSH) levels and PDA intervention restored the same. PDA treatment ameliorated TAA-induced collagen deposition and infiltration of inflammatory cells as revealed by Sirius red and H&E staining. Additionally, histopathological analysis revealed lymphocyte infiltration, collagen build up, development of bridging fibrosis, degeneration of the portal triad, iron accumulation, and necrosis in TAA-treated rats. The intervention with PDA significantly mitigated these pathological changes. PDA treatment significantly downregulated the expressions of TGF-β1, α-SMA, NLRP3, NF-κB and HDAC6 against TAA-induced liver damage. The present study clearly demonstrated that PDA treatment significantly alleviated TAA-induced hepatic fibrosis by ameliorating the inflammatory markers.