Wang Yan, Feng Shaohua, Du Qian, Liu Yiwei, Qin Chuanjie, Wu Bangyuan
Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
Key Laboratory of Southwest China Wildlife Resources Conservation, Ministry of Education, Nanchong, 637000, Sichuan, China.
Biol Trace Elem Res. 2024 Oct 8. doi: 10.1007/s12011-024-04408-w.
Nickel (Ni) is a human carcinogen that causes oxidative damage to many organs, and methionine has been studied to protect mammals from similar toxic effects by other heavy metals possibly through sulfur metabolism. This study aimed to investigate the protective effects of methionine on Ni-induced injuries to the kidneys. In this study, the mice were randomly divided into BC (normal diet), MD (methionine deficiency diet), MN (methionine plus nickel diet), and MDN (methionine deficiency plus nickel diet) treatment groups. Their renal function, histological changes, cell cycle, apoptosis, oxidative damage, and NF-κB inflammatory cytokines were detected after 21 days by HE, immunohistochemistry, TUNEL staining, and biochemical and ELISA methods. The results showed that serum Cr, BUN, and the NAG content increased in MDN (P < 0.01), MN (P < 0.05), and MD (P < 0.05) group mice compared to BC group mice. Glomerulus atrophy and renal tubular atrophy were observed in the MDN, MN, and MD groups but less severe in MN group mice. The PCNA protein content was the highest in BC group mice followed by MD, MN, and MDN. The activities of antioxidant enzymes (SOD, CAT, GSH, GSH-Px, and GSH-ST) were lower significantly in MD, MN, and MDN group mice, and the oxidant products content (MDA, LPO, and ROS) in the BC group were higher than those in other groups with a similar trend. The contents of NF-κB, TNF-α, IFN-γ, IL-1a, and IL-6 in the BC group were found to increase significantly in MD, MN, and MDN groups. In conclusion, Ni-induced kidney injury was indicated by renal tissue and cell damage, increased kidney metabolism products release in the serum, and renal oxidative stress while methionine addition helped alleviate the injury. In addition, the NF-κB signal pathway was involved in the renal inflammatory reaction induced by Ni where methionine helped mitigate it.
镍（Ni）是一种人类致癌物，会对许多器官造成氧化损伤，并且已经对蛋氨酸进行了研究，其可能通过硫代谢保护哺乳动物免受其他重金属类似的毒性作用。本研究旨在探讨蛋氨酸对镍诱导的肾脏损伤的保护作用。在本研究中，将小鼠随机分为BC（正常饮食）、MD（蛋氨酸缺乏饮食）、MN（蛋氨酸加镍饮食）和MDN（蛋氨酸缺乏加镍饮食）治疗组。21天后，通过苏木精-伊红（HE）染色、免疫组织化学、TUNEL染色以及生化和酶联免疫吸附测定（ELISA）方法检测它们的肾功能、组织学变化、细胞周期、细胞凋亡、氧化损伤和核因子κB（NF-κB）炎性细胞因子。结果显示，与BC组小鼠相比，MDN组（P＜0.01）、MN组（P＜0.05）和MD组（P＜0.05）小鼠的血清肌酐（Cr）、尿素氮（BUN）和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）含量升高。在MDN组、MN组和MD组中观察到肾小球萎缩和肾小管萎缩，但MN组小鼠的情况较轻。增殖细胞核抗原（PCNA）蛋白含量在BC组小鼠中最高，其次是MD组、MN组和MDN组。MD组、MN组和MDN组小鼠中抗氧化酶（超氧化物歧化酶（SOD）﹑过氧化氢酶（CAT）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）和谷胱甘肽S-转移酶（GSH-ST））的活性显著降低，并且BC组中的氧化产物含量（丙二醛（MDA）、脂质过氧化物（LPO）和活性氧（ROS））高于其他组，趋势相似。发现BC组中的NF-κB、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素-1α（IL-1α）和白细胞介素-6（IL-6）含量在MD组、MN组和MDN组中显著增加。总之，肾脏组织和细胞损伤、血清中肾脏代谢产物释放增加以及肾脏氧化应激表明镍诱导的肾脏损伤，而添加蛋氨酸有助于减轻损伤。此外，NF-κB信号通路参与了镍诱导的肾脏炎症反应，蛋氨酸有助于减轻这种反应。
