Bkhairia Intidhar, Dhibi Sabah, Nasri Rim, Elfeki Abdelfettah, Hfaiyedh Najla, Ben Amara Ibtissem, Nasri Moncef
Laboratory of Enzyme Engineering and Microbiology, University of Sfax, National School of Engineering of Sfax (ENIS) B. P. 1173 3038 Sfax Tunisia
Laboratory of Environmental Physiopathology, Valorization of Bioactive Molecules and Mathematical Modeling, Faculty of Sciences of Sfax Road Soukra km 3.5 PB no. 1171-14 3000 Sfax Tunisia.
RSC Adv. 2018 Jun 26;8(41):23230-23240. doi: 10.1039/c8ra02178c. eCollection 2018 Jun 21.
This study was undertaken to examine the hepatoprotective, antioxidant, and DNA damage protective effects of protein hydrolysates from , against paracetamol overdose induced liver injury in Wistar rats. 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 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.
本研究旨在考察[具体来源]的蛋白质水解产物对扑热息痛过量诱导的Wistar大鼠肝损伤的保肝、抗氧化及DNA损伤保护作用。[具体来源]蛋白质水解产物（LAPHs）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）。通过尺寸排阻色谱法测定水解产物的分子量分布，该方法分析了一种代表性的水解产物类型，其重量范围为3 - 20 kDa。通过[具体检测方法]检测LAPHs对扑热息痛肝毒性的保肝作用。大鼠每天经口灌胃给予LAPHs，持续45天。在治疗的最后五天，通过腹腔注射给大鼠施用扑热息痛。扑热息痛过量导致大鼠明显肝损伤，表现为血清天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）活性显著升高，以及氧化应激，这从酶促抗氧化剂（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））活性降低、谷胱甘肽（GSH）水平降低以及脂质过氧化产物（MDA）浓度升高可以明显看出。此外，扑热息痛增加了DNA损伤并伴有肝脏组织病理学变化。LAPH预处理显著减轻了扑热息痛诱导的肝毒性作用，包括氧化损伤、组织病理学病变以及肝组织中的凋亡变化。有趣的是，LAPHs恢复了抗氧化酶的活性和GSH水平，改善了肝细胞的组织学和分子方面。目前的数据表明，高剂量扑热息痛在肝脏的氧化损伤和遗传毒性中起关键作用，因此，一些抗氧化剂如LAPHs可能作为保肝剂是安全的。总之，我们的研究提供了一致的证据，证明LAPHs对用有毒剂量扑热息痛治疗的动物具有有益作用，并可能鼓励进行临床试验。
