Division of Biotechnology, Lupin Limited, Pune, India.
Faculty of Health Sciences, Symbiosis School of Biological Sciences, Selvan Ravindran, Symbiosis International (Deemed) University, Pune, India.
Curr Pharm Biotechnol. 2022;23(7):970-977. doi: 10.2174/1389201022666210810141139.
One of the most commonly used anti-cancer agents, Cisplatin (CDDP) often causes nephrotoxicity by eliciting inflammation and oxidative stress. Golimumab, an anti-TNF biologic, is prescribed for the management of numerous inflammatory ailments like psoriatic and rheumatoid arthritis, ulcerative colitis and ankylosing spondylitis.
Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity.
Renal toxicity was caused by administration of single cisplatin injection at 22 mg/kg by intraperitoneal (i/p) route. Golimumab (24 mg/kg, s.c.) was administered consecutively for 7 days. The parameters such as renal functions, oxidative stress, inflammation, and renal damage were evaluated on the 7th day of experiments.
Cisplatin administration caused nephrotoxicity as shown by a significant elevation of various parameters viz; serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urea nitrogen (BUN), and cystatin C. There was a significant rise in urinary clusterin, kidney injury molecule 1 (KIM-1), and β-N-acetylglucosaminidase (NAG) concentrations in the animals treated with cisplatin. The markers of oxidative stress (malondialdehyde, reduced glutathione, and catalase), inflammation (IL-6, TNF-α, IL-10, IL-1β, MCP-1, ICAM-1, and TGF-β1), and apoptosis (caspase-3) were also altered in serum and/or kidneys of cisplatin animals. Further, cisplatin-caused histopathological changes in proximal tubular cells as observed in the H&E staining of renal tissue. Golimumab treatment reduced all markers of kidney injury and attenuated cell death. Golimumab significantly reduced inflammatory cytokines TNFα, IL- 6, MCP-1, IL- 1β, ICAM-1, and TGF-β1 and increased anti-inflammatory cytokine IL-10 in cisplatin-intoxicated mice.
The study's results suggest that golimumab prevented nephrotoxicity induced by cisplatin- through inhibition of oxidative stress, apoptotic cell death inflammatory response, thus improving renal function.
顺铂（CDDP）是最常用的抗癌药物之一，常通过引发炎症和氧化应激引起肾毒性。戈利木单抗是一种抗 TNF 生物制剂，用于治疗多种炎症性疾病，如银屑病关节炎、类风湿关节炎、溃疡性结肠炎和强直性脊柱炎。
本研究探讨了抗 TNF 生物制剂戈利木单抗对顺铂诱导的肾毒性小鼠的影响。
通过腹腔内（i/p）途径给予单剂量顺铂 22mg/kg 造成肾毒性。连续 7 天给予戈利木单抗（24mg/kg，皮下）。在实验的第 7 天评估肾功能、氧化应激、炎症和肾损伤等参数。
顺铂给药导致肾毒性，表现为各种参数显著升高，如血清肌酐、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、尿素氮（BUN）和胱抑素 C。顺铂处理的动物尿中簇蛋白、肾损伤分子 1（KIM-1）和 β-N-乙酰氨基葡萄糖苷酶（NAG）浓度显著升高。血清和/或肾脏中的氧化应激标志物（丙二醛、还原型谷胱甘肽和过氧化氢酶）、炎症标志物（IL-6、TNF-α、IL-10、IL-1β、MCP-1、ICAM-1 和 TGF-β1）和凋亡标志物（caspase-3）也发生改变。此外，顺铂引起的组织病理学变化在肾组织的 H&E 染色中观察到近端肾小管细胞。戈利木单抗治疗降低了所有肾损伤标志物，并减轻了细胞死亡。戈利木单抗显著降低了顺铂中毒小鼠的炎症细胞因子 TNFα、IL-6、MCP-1、IL-1β、ICAM-1 和 TGF-β1，并增加了抗炎细胞因子 IL-10。
该研究结果表明，戈利木单抗通过抑制氧化应激、细胞凋亡、炎症反应，防止顺铂引起的肾毒性，从而改善肾功能。
