Jabbar Ahmed A J, Alamri Zaenah Zuhair, Abdulla Mahmood Ameen, AlRashdi Ahmed S, Najmaldin Soran Kayfi, Zainel Mustafa AbdulMonam
Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil 44001, Iraq.
Department of Biological Sciences, Faculty of Science, University of Jeddah, Jeddah 23218, Saudi Arabia.
Biomedicines. 2023 May 15;11(5):1447. doi: 10.3390/biomedicines11051447.
Sinapic acid (SA) is a natural pharmacological active compound found in berries, nuts, and cereals. The current study aimed to investigate the protective effects of SA against thioacetamide (TAA) fibrosis in rats by histopathological and immunohistochemical assays. The albino rats (30) were randomly divided into five groups (G). G1 was injected with distilled water 3 times/week and fed orally daily with 10% Tween 20 for two months. G2-5 were injected with 200 mg/kg TAA three times weekly for two months and fed with 10% Tween 20, 50 mg/kg silymarin, 20, and 40 mg/kg of SA daily for 2 months, respectively. The results showed that rats treated with SA had fewer hepatocyte injuries with lower liver index (serum bilirubin, total protein, albumin, and liver enzymes (ALP, ALT, and AST) and were similar to that of control and silymarin-treated rats. Acute toxicity for 2 and 4 g/kg SA showed to be safe without any toxic signs in treated rats. Macroscopic examination showed that hepatotoxic liver had an irregular, rough surface with micro and macro nodules and histopathology expressed by Hematoxylin and Eosin, and Masson Trichrome revealed severe inflammation and infiltration of focal necrosis, fibrosis, lymphocytes, and proliferation bile duct. In contrast, rats fed with SA had significantly lower TAA toxicity in gross and histology and liver tissues as presented by less liver tissue disruption, lesser fibrosis, and minimum in filtered hepatocytes. Immunohistochemistry of rats receiving SA showed significant up-regulation of HSP 70% and down-regulation of alpha-smooth muscle actin (α-SMA) protein expression compared to positive control rats. The homogenized liver tissues showed a notable rise in the antioxidant enzymes (SOD and CAT) actions with significantly lower malondialdehyde (MDA) levels compared to that of the positive control group. Furthermore, the SA-treated rats had significantly lower TNF-a, IL-6, and higher IL-10 levels than the positive control rats. Thus, the findings suggest SA as a hepatoprotective compound due to its inhibitory effects on fibrosis, hepatotoxicity, liver cell proliferation, up-regulation of HSP 70, and downregulation of α-SMA expression, inhibiting lipid peroxidation (MDA), while retaining the liver index and antioxidant enzymes to normal.
芥子酸（SA）是一种存在于浆果、坚果和谷物中的天然药理活性化合物。本研究旨在通过组织病理学和免疫组织化学分析，探讨SA对大鼠硫代乙酰胺（TAA）纤维化的保护作用。将30只白化大鼠随机分为五组（G）。G1组每周注射3次蒸馏水，每天口服10%吐温20，持续两个月。G2 - 5组每周注射3次200 mg/kg TAA，持续两个月，并分别每天口服10%吐温20、50 mg/kg水飞蓟宾、20 mg/kg和40 mg/kg的SA，持续2个月。结果表明，SA处理的大鼠肝细胞损伤较少，肝脏指数较低（血清胆红素、总蛋白、白蛋白和肝酶（碱性磷酸酶、谷丙转氨酶和谷草转氨酶）），与对照组和水飞蓟宾处理的大鼠相似。2 g/kg和4 g/kg SA的急性毒性试验表明，处理后的大鼠安全，无任何中毒迹象。肉眼检查显示，肝毒性肝脏表面不规则、粗糙，有微小结节和大结节，苏木精和伊红染色及Masson三色染色的组织病理学表现为严重炎症、局灶性坏死、纤维化、淋巴细胞浸润和胆管增生。相比之下，喂食SA的大鼠在大体和组织学以及肝脏组织中的TAA毒性显著降低，表现为肝组织破坏较少、纤维化较轻，肝细胞坏死最少。与阳性对照组大鼠相比，接受SA的大鼠免疫组织化学显示热休克蛋白（HSP）上调70%，α - 平滑肌肌动蛋白（α - SMA）蛋白表达下调。肝脏组织匀浆显示抗氧化酶（超氧化物歧化酶和过氧化氢酶）活性显著升高，丙二醛（MDA）水平显著低于阳性对照组。此外，SA处理的大鼠肿瘤坏死因子 - α、白细胞介素 - 6水平显著低于阳性对照组，白细胞介素 - 10水平较高。因此，研究结果表明SA是一种肝脏保护化合物，因为它对纤维化、肝毒性、肝细胞增殖具有抑制作用，上调HSP 70，下调α - SMA表达，抑制脂质过氧化（MDA），同时使肝脏指数和抗氧化酶保持正常。
