Aabis Mohammad, Tiwari Priyanka, Kumar Vinod, Singh Gurpreet, Panghal Archana, Jena Gopabandhu
Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Punjab, 160062, India.
High resolution Transmission electron microscopy Facility, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali (near to Chandigarh), Punjab, 160062, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 1. doi: 10.1007/s00210-025-04143-6.
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.
十五烷酸（PDA）已被报道为一种组蛋白去乙酰化酶6抑制剂。大量研究表明，组蛋白去乙酰化酶（HDACs）在纤维化发展过程中起着重要作用。本研究聚焦于评估PDA对改善硫代乙酰胺（TAA）诱导的Wistar大鼠肝纤维化的抗纤维化特性。PDA以每日10、20和40 mg/kg的剂量口服给药，而TAA以200 mg/kg的剂量每周两次腹腔注射给药，持续9周。给予TAA显著增加了相对和绝对肝脏重量、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）、γ-谷氨酰转移酶（γ-GT）、髓过氧化物酶（MPO）、丙二醛（MDA），并降低了谷胱甘肽（GSH）水平，而PDA干预使其恢复正常。天狼星红和苏木精-伊红染色显示，PDA治疗改善了TAA诱导的胶原沉积和炎性细胞浸润。此外，组织病理学分析显示，TAA处理的大鼠存在淋巴细胞浸润、胶原堆积、桥接纤维化形成、门三联体变性、铁蓄积和坏死。PDA干预显著减轻了这些病理变化。PDA治疗显著下调了TGF-β1、α-SMA、NLRP3、NF-κB和HDAC6在TAA诱导的肝损伤中的表达。本研究清楚地表明，PDA治疗通过改善炎症标志物显著减轻了TAA诱导的肝纤维化。
