Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate–cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.

中文翻译：

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柠檬提取物通过上调老年大鼠 Nrf2 和 Trx1 表达来降低肝脏氧化应激和过硫化水平

在健康老龄化的概念中，柑橘黄烷酮被认为是有前途的生物活性物质。因此，本研究调查了营养相关剂量的柠檬提取物 (LE) 对 24 个月大 Wistar 大鼠肝脏氧化还原调节和过硫化水平的影响。LE（40 mg/kg bm）每天口服一次，持续 4 周。对照组接受载体（葵花籽油）或保持完整。应用的方法考虑了qPCR、蛋白质印迹、蛋白质过硫化水平评估、符合免疫荧光的组织化学、肝脏生化测定（谷胱甘肽、总-SH基团和丙二醛；MDA）、血清中的肝酶和计算机分析，以探索潜在的相互作用/论文中研究的蛋白质之间的结合。我们的结果表明，LE 分别增加了谷胱甘肽过氧化物酶 (GPx)、还原酶 (GR)、谷氨酸-半胱氨酸连接酶催化亚基和修饰亚基以及 Nrf2 基因表达，但降低了超氧化物歧化酶 2 (SOD2) 的表达。应用 LE 后，蛋白质表达显示 NRF2、SOD2、GPx、GR 和硫氧还蛋白 1 (Trx1) 上调。LE 显着降低了蛋白质过硫化水平和 MDA 浓度（细胞氧化损伤的标志物）。组织学分析显示肝脏组织结构正常，没有病理变化，与正常血清肝酶水平一致。获得的结果表明，LE 通过调节肝脏氧化还原调节因子 Nrf2 和 Trx1，减少氧化应激并改变过硫化水平，表明柠檬黄烷酮在老年肝脏中具有相当大的有益抗氧化潜力。