Department of Food Science & Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2023 Feb 16;28(4):1879. doi: 10.3390/molecules28041879.
This study investigated some possible mechanisms underlying the nephrotoxic effect of gold nanoparticles (AuNPs) in rats and compared the protective effects of selected known antioxidants-namely, melanin, quercetin (QUR), and α-lipoic acid (α-LA). Rats were divided into five treatment groups (eight rats per group): control, AuNPs (50 nm), AuNPs + melanin (100 mg/kg), AuNPs + QUR (200 mg/kg), and AuNPs + α-LA (200 mg/kg). All treatments were administered i.p., daily, for 30 days. AuNPs promoted renal glomerular and tubular damage and impaired kidney function, as indicated by the higher serum levels of creatinine (Cr), urinary flow, and urea and albumin/Cr ratio. They also induced oxidative stress by promoting mitochondrial permeability transition pore (mtPTP) opening, the expression of NOX4, increasing levels of malondialdehyde (MDA), and suppressing glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). In addition, AuNPs induced renal inflammation and apoptosis, as evidenced by the increase in the total mRNA and the cytoplasmic and nuclear levels of NF-κB, mRNA levels of Bax and caspase-3, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Treatment with melanin, QUR, and α-lipoic acid (α-LA) prevented the majority of these renal damage effects of AuNPs and improved kidney structure and function, with QUR being the most powerful. In conclusion, in rats, AuNPs impair kidney function by provoking oxidative stress, inflammation, and apoptosis by suppressing antioxidants, promoting mitochondrial uncoupling, activating NF-κB, and upregulating NOX4. However, QUR remains the most powerful drug to alleviate this toxicity by reversing all of these mechanisms.
本研究探讨了金纳米粒子（AuNPs）在大鼠体内肾毒性的一些可能机制，并比较了几种已知抗氧化剂——黑色素、槲皮素（QUR）和α-硫辛酸（α-LA）——的保护作用。大鼠被分为五组（每组 8 只）：对照组、AuNPs（50nm）组、AuNPs+黑色素（100mg/kg）组、AuNPs+QUR（200mg/kg）组和 AuNPs+α-LA（200mg/kg）组。所有治疗均通过腹腔注射，每天一次，共 30 天。AuNPs 导致肾小球和肾小管损伤，肾功能受损，表现为血清肌酐（Cr）、尿流量和尿素及白蛋白/ Cr 比值升高。它们还通过促进线粒体通透性转换孔（mtPTP）开放、NOX4 表达、增加丙二醛（MDA）水平和抑制谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）来诱导氧化应激。此外，AuNPs 诱导肾炎症和细胞凋亡，这表现在 NF-κB 的总 mRNA 及其细胞质和核水平、Bax 和 caspase-3 的 mRNA 水平以及肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平的增加。黑色素、QUR 和 α-LA 的治疗预防了 AuNPs 对大多数这些肾损伤作用，并改善了肾脏结构和功能，其中 QUR 最为有效。总之，在大鼠中，AuNPs 通过抑制抗氧化剂、促进线粒体解偶联、激活 NF-κB 和上调 NOX4 来引发氧化应激、炎症和细胞凋亡，从而损害肾功能。然而，QUR 仍然是通过逆转所有这些机制来缓解这种毒性的最有效药物。
