Yousef Mokhtar Ibrahim, Khalil Dina K A M, Abdou Heba M
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.
Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Toxicol Rep. 2018 Apr 30;5:568-578. doi: 10.1016/j.toxrep.2018.04.006. eCollection 2018.
The combination of thalidomide and carboplatin is one of the most potent chemotherapeutic strategies for the treatment of cancer. However, limited studies have been conducted on the neurotoxicity and nephrotoxicity of both chemotherapeutic agents. The aim of our study was to assess the toxicity of thalidomide and carboplatin combination on brain and kidney and investigate the protective effect of grape seed proanthocyanidin extract (GSPE). Thalidomide and carboplatin induced up-regulation of the expression of p53, tumor necrosis factor-α and interleukin-6 in brain and kidney. Acetylcholinesterase, dopamine and serotonin were decreased and norepinephrine was increased. Thiobarbituric acid reactive substances, nitric oxide, lipid profile, bilirubin and creatinine were elevated, while antioxidants enzymes (GST, GPX, CAT and SOD), total antioxidant capacity and the levels of glutathione were decreased. A microscopic examination showed shrinkage of capillaries, degeneration with pyknotic nuclei, loss of normal structure and neuronal degeneration. GSPE co-treatment with thalidomide and carboplatin reduced their brain and renal damage, oxidative stress, diminished cytokines, p53, neurotransmitters and biochemical parameters, and inhibited brain and renal cell apoptosis. It can be concluded that, the protective effects of GSPE against thalidomide and carboplatin induced-brain and renal damage was associated with the minimization of oxidative stress.
沙利度胺与卡铂联合使用是治疗癌症最有效的化疗策略之一。然而，针对这两种化疗药物的神经毒性和肾毒性的研究较少。我们研究的目的是评估沙利度胺与卡铂联合用药对脑和肾的毒性，并研究葡萄籽原花青素提取物（GSPE）的保护作用。沙利度胺和卡铂可诱导脑和肾中p53、肿瘤坏死因子-α和白细胞介素-6的表达上调。乙酰胆碱酯酶、多巴胺和血清素减少，去甲肾上腺素增加。硫代巴比妥酸反应物质、一氧化氮、血脂、胆红素和肌酐升高，而抗氧化酶（谷胱甘肽S-转移酶、谷胱甘肽过氧化物酶、过氧化氢酶和超氧化物歧化酶）、总抗氧化能力和谷胱甘肽水平降低。显微镜检查显示毛细血管收缩、核固缩变性、正常结构丧失和神经元变性。GSPE与沙利度胺和卡铂联合治疗可减轻它们对脑和肾的损害、氧化应激，减少细胞因子、p53、神经递质和生化参数，并抑制脑和肾细胞凋亡。可以得出结论，GSPE对沙利度胺和卡铂诱导的脑和肾损伤的保护作用与氧化应激的最小化有关。
