Mona A H Yehia, Kawther M Foud, Hanan A El Sayed, Hagar M Mohamed, Ahmad M Attia
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引用次数: 0
Abstract
Cyclosporine A (CsA) is a powerful immunosuppressant drug most widely used in managing organ transplantation and autoimmune diseases. The aim of this work was to investigate the role of taurine in alleviating the apoptotic hepatocytes and oxidative stress caused by CsA in rats' livers. The four experimental groups were evaluated, including (GpI) vehicle control (olive oil), (GpII) Tau (5 mg/kg/day), (GpIII) CsA (50 mg/kg/day), and (GpIV) CsA + Tau. The biochemical assay in liver functions and antioxidant enzymes was assayed, and the histopathology of hepatic tissue and immunohistochemical staining of apoptotic protein (p53) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were determined. Induction of CsA in rats caused severe hepatotoxicity, as evidenced by the elevation of serum aspartate aminotransferase, alanine aminotransferase activities, and alkaline phosphatase concentration and decreased catalase (CAT), glutathione peroxidase, and glutathione reductase activities. The histopathological examination revealed mild to marked disorganization in the liver tissue, characterized by hepatocyte degeneration/necrosis, apoptotic hepatocytes, sinusoidal dilatation, and inflammatory cell infiltration. Whereas Tau treatment improved the liver function enzymes and increased the oxidative stress by elevating the antioxidant enzyme CAT and glutathione reductase. There is recovery of destructive liver tissue preserved hepatic trabecular architecture; dark nuclei with prominent nucleoli, hepatocytes, and mild dilated sinusoids; small area of pyknotic hepatocytes have vacuolated cytoplasm was seen, and the number of apoptotic cells detected by TUNEL and p53 protein was significantly decreased (P = .001). The results may contribute to the hepatoprotective role of Tau and its ability to ameliorate the oxidative stress and alleviate the apoptotic hepatocytes induced by CsA. So, Tau may have had a beneficial role in reducing tissue damage in patients exposed to CsA.
环孢素A (Cyclosporine A, CsA)是一种强大的免疫抑制药物,广泛用于器官移植和自身免疫性疾病的治疗。本研究旨在探讨牛磺酸在减轻CsA引起的肝细胞凋亡和氧化应激中的作用。对(GpI)对照(橄榄油)、(GpII) Tau (5 mg/kg/d)、(GpIII) CsA (50 mg/kg/d)和(GpIV) CsA + Tau四个实验组进行评价。进行肝功能、抗氧化酶生化检测,肝组织病理学检测及凋亡蛋白(p53)、末端脱氧核苷酸转移酶dUTP nick end labeling (TUNEL)免疫组化染色。CsA诱导大鼠产生严重的肝毒性,血清天冬氨酸转氨酶、丙氨酸转氨酶活性和碱性磷酸酶浓度升高,过氧化氢酶(CAT)、谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性降低。组织病理学检查显示肝组织轻度至明显紊乱,表现为肝细胞变性/坏死、肝细胞凋亡、肝窦扩张、炎症细胞浸润。而Tau处理通过提高抗氧化酶CAT和谷胱甘肽还原酶,改善肝功能酶,增加氧化应激。破坏肝组织恢复,保留肝小梁结构;细胞核暗,核仁、肝细胞明显,窦状窦轻度扩张;肝细胞小面积缩缩,胞浆空泡化,TUNEL及p53蛋白检测的凋亡细胞数量明显减少(P = 0.001)。这些结果可能与Tau的肝保护作用及其改善氧化应激和减轻CsA诱导的肝细胞凋亡的能力有关。因此,Tau可能在减少暴露于CsA的患者的组织损伤方面发挥了有益的作用。
期刊介绍:
Journal of Medicinal Food is the only peer-reviewed journal focusing exclusively on the medicinal value and biomedical effects of food materials. International in scope, the Journal advances the knowledge of the development of new food products and dietary supplements targeted at promoting health and the prevention and treatment of disease.