Liver fibrosis is a major health issue leading to high morbidity and mortality. The potential anti-fibrotic activity and the effect of mesalazine on osteopontin (OPN), an extra cellular matrix (ECM) component were evaluated in TAA-induced liver fibrosis in rats. For this purpose, forty-two adult male Wistar rats were divided into six groups. All animals, except the normal control, were intraperitoneally injected with TAA (200 mg/kg) twice per week for 6 weeks. In the hepato-protective study, animals were administered mesalazine (50 and 100 mg/kg, orally) for 4 weeks before induction of liver fibrosis then concomitantly with TAA injection. In the hepato-therapeutic study, animals were administered mesalazine for 6 weeks after TAA discontinuation with the same doses. In both studies, mesalazine administration improved liver biomarkers through decreasing serum levels of AST, ALT and total bilirubin when compared to fibrotic group with significant increase in total protein and albumin levels. Mesalazine significantly decreased hepatic MDA level and counteracted the depletion of hepatic GSH content and SOD activity. Additionally, it limits the elevation of OPN and TGF-β1 concentrations and suppressed TNF-α as well as α-SMA levels in hepatic tissue homogenate. Histopathologically, mesalazine as a treatment showed a good restoration of the hepatic parenchymal cells with an obvious decreased intensity and retraction of fibrous proliferation, while as a prophylaxis it didn't achieve enough protection against the harmful effect of TAA, although it decreased the intensity of portal to portal fibrosis and pseudolobulation. Furthermore, mesalazine could suppress the expression of both α-SMA and caspase-3 in immunohistochemical sections. In conclusion, mesalazine could have a potential new indication as anti-fibrotic agent through limiting the oxidative damage and altering TNF-ɑ pathway as an anti-inflammatory drug with down-regulating TGF-β1, OPN, α-SMA and caspase-3 signaling pathways.

肝纤维化是导致高发病率和高死亡率的主要健康问题。在TAA诱导的大鼠肝纤维化中评估了潜在的抗纤维化活性以及美沙拉嗪对骨桥蛋白（OPN）和骨桥蛋白（ECM）的影响，骨桥蛋白是一种额外的细胞基质（ECM）成分。为此，将四十二只成年雄性Wistar大鼠分成六组。除正常对照组外，所有动物每周两次腹膜内注射TAA（200 mg / kg），持续6周。在保护肝脏的研究中，在诱导肝纤维化之前，先给动物服用美沙拉嗪（50和100 mg / kg，口服）达4周，然后再注射TAA。在肝治疗研究中，以相同剂量在TAA停用后对动物给予美沙拉嗪治疗6周。在两项研究中 与纤维化组相比，美沙拉嗪的给药通过降低血清AST，ALT和总胆红素水平来改善肝脏生物标志物，总蛋白和白蛋白水平显着增加。美沙拉嗪显着降低了肝脏MDA水平，并抵消了肝脏GSH含量和SOD活性的消耗。此外，它限制了肝组织匀浆中OPN和TGF-β1浓度的升高，并抑制了TNF-α和α-SMA的水平。从组织病理学上看，美沙拉嗪作为一种治疗方法能够很好地恢复肝实质细胞，强度明显降低，并且纤维增殖抑制，尽管作为预防措施，尽管它降低了TAA的强度，但仍未获得足够的针对TAA有害作用的保护作用。门静脉纤维化和假小叶形成。此外，美沙拉嗪可以抑制免疫组织化学切片中α-SMA和caspase-3的表达。总之，美沙拉嗪可能通过限制氧化损伤并改变TNF-ɑ途径作为抗炎药，具有下调TGF-β1，OPN，α-SMA和caspase-3信号传导的潜力，作为抗纤维化药具有潜在的新适应症。途径。