Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
Department of Chemistry, College of Science, King Khalid University, Abha, Kingdom of Saudi Arabia.
PLoS One. 2021 Dec 29;16(12):e0260130. doi: 10.1371/journal.pone.0260130. eCollection 2021.
The objective of the current study is to investigate the effect of rice bran oil (RBO) on hepatic fibrosis as a characteristic response to persistent liver injuries. Rats were randomly allocated into five groups: the negative control group, thioacetamide (TAA) group (thioacetamide 100 mg/kg thrice weekly for two successive weeks, ip), RBO 0.2 and 0.4 groups (RBO 0.2mL and 0.4 mL/rat/day, po) and standard group (silymarin 100 mg/kg/day, po) for two weeks after TAA injection. Blood and liver tissue samples were collected for biochemical, molecular, and histological analyses. Liver functions, oxidative stress, inflammation, liver fibrosis markers were assessed. The obtained results showed that RBO reduced TAA-induced liver fibrosis and suppressed the extracellular matrix formation. Compared to the positive control group, RBO dramatically reduced total bilirubin, AST, and ALT blood levels. Furthermore, RBO reduced MDA and increased GSH contents in the liver. Simultaneously RBO downregulated the NF-κβ signaling pathway, which in turn inhibited the expression of some inflammatory mediators, including Cox-2, IL-1β, and TNF-α. RBO attenuated liver fibrosis by suppressing the biological effects of TGF-β1, α-SMA, collagen I, hydroxyproline, CTGF, and focal adhesion kinase (FAK). RBO reduced liver fibrosis by inhibiting hepatic stellate cell activation and modulating the interplay among the TGF-β1 and FAK signal transduction. The greater dosage of 0.4 mL/kg has a more substantial impact. Hence, this investigation presents RBO as a promising antifibrotic agent in the TAA model through inhibition of TGF-β1 /FAK/α-SMA.
本研究旨在探讨米糠油(RBO)对肝纤维化的影响,肝纤维化是对持续性肝损伤的特征性反应。大鼠被随机分为五组:阴性对照组、硫代乙酰胺(TAA)组(TAA 100mg/kg,每周三次,连续两周,ip)、RBO0.2 和 0.4 组(RBO0.2 和 0.4mL/大鼠/天,po)和标准组(水飞蓟素 100mg/kg/天,po),在 TAA 注射后两周。收集血液和肝组织样本进行生化、分子和组织学分析。评估肝功能、氧化应激、炎症、肝纤维化标志物。结果表明,RBO 可减轻 TAA 诱导的肝纤维化并抑制细胞外基质形成。与阳性对照组相比,RBO 显著降低总胆红素、AST 和 ALT 血液水平。此外,RBO 降低 MDA 并增加肝中 GSH 含量。同时,RBO 下调 NF-κβ信号通路,从而抑制一些炎症介质的表达,包括 Cox-2、IL-1β 和 TNF-α。RBO 通过抑制 TGF-β1、α-SMA、胶原 I、羟脯氨酸、CTGF 和粘着斑激酶(FAK)的生物学作用来减轻肝纤维化。RBO 通过抑制肝星状细胞激活和调节 TGF-β1/FAK 信号转导之间的相互作用来减轻肝纤维化。较大剂量 0.4mL/kg 的影响更大。因此,本研究表明 RBO 是 TAA 模型中一种有前途的抗纤维化剂,通过抑制 TGF-β1/FAK/α-SMA。