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Bioactive properties: enhancement of hepatoprotective, antioxidant and DNA damage protective effects of golden grey mullet protein hydrolysates against paracetamol toxicity

机译:生物活性:增强金黄色鱼蛋白水解物的肝保护,抗氧化剂和DNA损伤的保护作用,以对抗对乙酰氨基酚毒性

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This study was undertaken to examine the hepatoprotective, antioxidant, and DNA damage protective effects of protein hydrolysates from Liza aurata , against paracetamol overdose induced liver injury in Wistar rats. L. aurata protein hydrolysates (LAPHs) were mainly constituted by glutamic acid (Glu) and glutamine (Gln) and lysine (Lys). In addition, they contained high amounts of proline (Pro), leucine (Leu) and glycine (Gly). The molecular weight distribution of the hydrolysates was determined by size exclusion chromatography, which analyzed a representative hydrolysate type with a weight range of 3–20 kDa. The hepatoprotective effect of LAPHs against paracetamol liver toxicity was investigated by in vivo assay. Rats received LAPHs daily by gavage, for 45 days. Paracetamol was administrated to rats during the last five days of treatment by intraperitoneal injection. Paracetamol overdose induced marked liver damage in rats was noted by a significant increase in the activities of serum aspartate amino transferase (AST) and alanine amino transferase (ALT), and oxidative stress which was evident from decreased activity of the enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and level of glutathione (GSH), and increased concentration of lipid peroxidation products (MDA). Furthermore, paracetamol increased the DNA damage with liver histopathological changes. LAPH pretreatment significantly attenuated paracetamol-induced hepatotoxic effects, including oxidative damage, histopathological lesions, and apoptotic changes in the liver tissue. Interestingly, LAPHs restored the activities of antioxidant enzymes and the level of GSH, ameliorated histological and molecular aspects of liver cells. The present data suggest that paracetamol high-dose plays a crucial role in the oxidative damage and genotoxicity of the liver and therefore, some antioxidants such us LAPHs might be safe as hepatoprotectors. Altogether, our studies provide consistent evidence of the beneficial effect of LAPHs on animals treated with a toxic dose of paracetamol and might encourage clinical trials.
机译:这项研究旨在检查Wistar大鼠对乙酰氨基酚过量引起的肝损伤中来自Liza aurata的蛋白水解产物的保肝,抗氧化和DNA损伤的保护作用。金黄色葡萄球菌蛋白水解物(LAPH)主要由谷氨酸(Glu),谷氨酰胺(Gln)和赖氨酸(Lys)组成。此外,它们还含有大量的脯氨酸(Pro),亮氨酸(Leu)和甘氨酸(Gly)。水解产物的分子量分布通过尺寸排阻色谱法确定,该色谱分析了重量范围为3–20 kDa的代表性水解产物类型。通过体内试验研究了LAPHs对扑热息痛肝脏毒性的保肝作用。大鼠每天通过管饲法接受LAPH,持续45天。在治疗的最后五天中,通过腹膜内注射对大鼠施用扑热息痛。血清中的天门冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)的活性显着增加,以及对氧化应激的影响,这表明对乙酰氨基酚过量导致大鼠肝损伤,氧化酶的抗氧化剂(超氧化物歧化酶( SOD),过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)),谷胱甘肽水平(GSH)和脂质过氧化产物(MDA)浓度增加。此外,扑热息痛可通过肝脏组织病理学改变增加DNA损伤。 LAPH预处理可显着减弱扑热息痛诱导的肝毒性作用,包括氧化损伤,组织病理学损害和肝组织凋亡变化。有趣的是,LAPHs恢复了抗氧化酶的活性和GSH的水平,改善了肝细胞的组织学和分子学方面。目前的数据表明,对乙酰氨基酚高剂量在肝脏的氧化损伤和遗传毒性中起着至关重要的作用,因此,某些抗氧化剂(例如LAPHs)作为保肝剂可能是安全的。总而言之,我们的研究提供了一致的证据,证明了LAPH对用中毒剂量对乙酰氨基酚治疗的动物的有益作用,并且可能会鼓励临床试验。

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