The Effect of Curcumin on Oxaliplatin and Cisplatin Neurotoxicity in Rats: Some Behavioral, Biochemical, and Histopathological Studies
The Effect of Curcumin on Oxaliplatin and Cisplatin Neurotoxicity in Rats: Some Behavioral, Biochemical, and Histopathological Studies
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DOI：
10.1007/s13181-012-0239-x
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Ali, Badreldin H.
中科院分区：
文献类型：
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作者：
Al Moundhri, Mansour S.;Al-Salam, Suhail;Ali, Badreldin H.
顺铂通常用于治疗几种实体瘤，奥沙利铂是一种有效的细胞毒药物，用于结直肠癌。在接受顺铂或奥沙利铂治疗的患者中，影响10%-40%的主要临床问题是导致感觉、运动和自主神经功能障碍的严重周围神经病变，症状包括感冒敏感和神经病理性疼痛。神经毒性的生化基础尚不确定，但与氧化应激有关。姜黄素是一种天然酚类黄色素，具有很强的抗氧化、抗癌、抗炎等作用。在此，我们报道了姜黄素对顺铂和奥沙利铂诱导的大鼠行为、生化和组织病理学改变的可能保护作用。治疗结束24小时后，进行一些运动和行为测试(运动活动、热和机械伤害性感觉、神经肌肉协调)，然后测定血浆神经降压素在坐骨神经中的铂浓度，并研究坐骨神经的组织病理学。奥沙利铂(4 mg/kg)和顺铂(2 mg/kg)[每周两次，在4.5周内共9次腹腔注射]显著增加了血浆神经降压素浓度，导致坐骨神经组织学损伤，并在运动和行为测试中产生不同的影响。口服姜黄素(10 mg/kg，给药前4d，给药后4.5周)逆转了铂治疗大鼠血浆神经降压素和坐骨神经铂浓度的变化，并显著改善了坐骨神经组织学。需要使用更大剂量范围的奥沙利铂、顺铂和姜黄素进行更大规模的实验，以充分阐明姜黄素在铂诱导的神经毒性中可能的保护作用。
Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions. Here we report the possible protective effect of curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and histopathological alterations in rats. Twenty-four hours after the end of treatments some motor and behavioral tests (motor activity, thermal and mechanical nociception, and neuromuscular coordination) were conducted, followed by measuring plasma neurotensin platinum concentration in the sciatic nerve, and studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal injections over 4.5 weeks] significantly increased plasma neurotensin concentration, caused specific damage in the histology of the sciatic nerve and produced variable effects in the motor and behavioral tests. Oral curcumin (10 mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for 4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve platinum concentrations, and markedly improved sciatic nerve histology in the platinum-treated rats. Larger experiments using a wider dose range of oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible protective role of curcumin in platinum-induced neurotoxicity.