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核桃种皮提取物对急性肾缺血/再灌注损伤的肝肾保护潜力。

The hepato-renal protective potential of walnut seed skin extract against acute renal ischemia/reperfusion damage.

作者信息

Askin Seda, Askin Hakan, Dursun Elifnur, Palabiyik Esra, Uguz Handan, Cakmak Özge, Koc Kubra

机构信息

Health Services Vocational School, Ataturk University, Erzurum, Turkey.

Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Turkey.

出版信息

Cytokine. 2022 May;153:155861. doi: 10.1016/j.cyto.2022.155861. Epub 2022 Mar 18.

Abstract

Acute kidney damage is defined as a sudden change in kidney functions that prevents the removal of nitrogenous wastes from the body, thus disrupting the body's fluid and electrolyte balance. When acute kidney injury occurs, the kidneys and liver are most affected in the body. Agents used in the treatment of acute kidney injury often have nonsteroidal anti-inflammatory properties that can produce toxic effects on the gastrointestinal tract and kidneys. Natural antioxidants can be recommended as an alternative to existing treatment or in combination to protect tissues against these toxic effects. Therefore, we conducted our current study on whether walnut seed skin (WSS) extract might have hepato-renal protective effects in kidney-damaged Sprague-Dawley rats. This study is the first to use walnut seed skin extract in liver and kidney tissues in renal ischemia/reperfusion (IR) injury. Female Sprague-Dawley rats were randomly divided into three groups: Healty control (HC), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 450 mg/kg/p.o. WSS extract (the rats were treated with WSS extract orally once 1 h before the IR procedure). For this purpose, blood, liver and kidney tissues of rats were used. In serum samples, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine values were determined separately for the administration groups. We also performed histopathological studies on liver and kidney tissues. Finally, gene markers (endothelial nitric oxide synthase (eNOS), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), Caspase-4 and Caspase-9) determined to evaluate the anti-oxidant, anti-inflammatory and apoptotic effect of walnut seed skin were measured by q-RT PCR method. As a result of the study it was determined that pre-application of WSS extract improved the deteriorated serum parameters in rats with renal ischemia. In the histopathological analysis results, it was observed that WSS had a protective effect on kidney and liver tissue. In studies on gene expression, although there were different and contradictory results for liver and kidney tissue, we determined that WSS was more protective on liver tissue. In conclusion, the healing potential of WSS in renal and hepatic tissues seems to act by inhibiting the inflammatory response, oxidative stress and apoptosis. Therefore, the potential of this extract is remarkable and may serve as a potential therapeutic that may protect against acute organ damages due to renal IR.

摘要

急性肾损伤被定义为肾功能的突然改变,这种改变会阻止身体排出含氮废物,从而扰乱身体的体液和电解质平衡。当发生急性肾损伤时,身体内的肾脏和肝脏受到的影响最大。用于治疗急性肾损伤的药物通常具有非甾体抗炎特性,可能会对胃肠道和肾脏产生毒性作用。可以推荐天然抗氧化剂作为现有治疗方法的替代方案,或者与现有治疗方法联合使用,以保护组织免受这些毒性作用。因此,我们开展了当前这项研究,以探究核桃种皮(WSS)提取物对肾损伤的Sprague-Dawley大鼠是否可能具有肝肾保护作用。本研究首次将核桃种皮提取物用于肾缺血/再灌注(IR)损伤的肝脏和肾脏组织。雌性Sprague-Dawley大鼠被随机分为三组:健康对照组(HC)、肾IR组(50分钟缺血 - 3小时再灌注)和肾IR + 450毫克/千克/口服WSS提取物组(在IR手术前1小时给大鼠口服一次WSS提取物)。为此,使用了大鼠的血液、肝脏和肾脏组织。在血清样本中,分别测定了给药组的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)、尿素和肌酐值。我们还对肝脏和肾脏组织进行了组织病理学研究。最后,通过q-RT PCR方法测定了基因标志物(内皮型一氧化氮合酶(eNOS)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、半胱天冬酶-4和半胱天冬酶-9),以评估核桃种皮的抗氧化、抗炎和凋亡作用。研究结果表明,预先应用WSS提取物改善了肾缺血大鼠恶化了的血清参数。在组织病理学分析结果中,观察到WSS对肾脏和肝脏组织具有保护作用。在基因表达研究中,尽管肝脏和肾脏组织的结果存在差异和矛盾,但我们确定WSS对肝脏组织的保护作用更强。总之,WSS在肾脏和肝脏组织中的修复潜力似乎是通过抑制炎症反应、氧化应激和凋亡来发挥作用的。因此,这种提取物的潜力显著,可能成为一种潜在的治疗方法,预防因肾IR导致的急性器官损伤。

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