The Effect of Curcumin on Oxaliplatin and Cisplatin Neurotoxicity in Rats: Some Behavioral, Biochemical, and Histopathological Studies

被引:106
作者
Al Moundhri M.S. [1 ]
Al-Salam S. [2 ]
Al Mahrouqee A. [3 ]
Beegam S. [3 ]
Ali B.H. [3 ]
机构
[1] Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod
[2] Department of Pathology, Faculty of Medicine, UAE University, Al Ain
[3] Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod, 123, SQU
关键词
Cisplatin; Curcumin; Neurotoxicity; Oxaliplatin; Rats;
D O I
10.1007/s13181-012-0239-x
中图分类号
学科分类号
摘要
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. © 2012 American College of Medical Toxicology.
引用
收藏
页码:25 / 33
页数:8
相关论文
共 39 条
[1]  
Saif M.W., Reardon J., Management of oxaliplatin-induced peripheral neuropathy, Ther Clin Risk Manag, 1, pp. 249-258, (2005)
[2]  
Shah N., Dizon D.S., New-generation platinum agents for solid tumors, Future Oncol, 5, pp. 33-42, (2009)
[3]  
Grothey A., Clinical management of oxaliplatin-associated neurotoxicity, Clin Colorectal Cancer, 5, SUPPL. 1, (2005)
[4]  
Broomand A., Jerremalm E., Yachnin J., Ehrsson H., Elinder F., Oxaliplatin neurotoxicity-no general ion channel surface-charge effect, J Negat Results Biomed, 8, (2009)
[5]  
Cavaletti G., Marmiroli P., Chemotherapy-induced peripheral neurotoxicity, Nature Review Neurology, 6, pp. 657-666, (2011)
[6]  
Holmes J., Stanko J., Varchenko M., Ding H., Madden V.J., Bagnell C.R., Wyrick S.D., Chaney S.G., Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model, Toxicol Sci, 46, pp. 342-351, (1998)
[7]  
Webster R.G., Brain K.L., Wilson R.H., Grem J.L., Vincent A., Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels, Br J Pharmacol, 146, pp. 1027-1039, (2005)
[8]  
Montagnani F., Turrisi G., Marinozzi C., Aliberti C., Fiorentini G., Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unrespectable gastric cancer: a systematic review and meta-analysis, Gastric Cancer, 14, pp. 50-55, (2011)
[9]  
Podratz J.L., Knight A.M., Ta L.E., Staff N.P., Gass J.M., Genelin K., Schlattau A., Lathroum L., Windebank A.J., Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons, Neurobiol Dis, 41, pp. 661-668, (2011)
[10]  
Shord S.S., Bernard S.A., Lindley C., Blodgett A., Mehta V., Churchel M.A., Poole M., Pescatore S.L., Luo F.R., Chaney S.G., Oxaliplatin biotransformation and pharmacokinetics: a pilot study to determine the possible relationship to neurotoxicity, Anticancer Res, 22, pp. 2301-2309, (2002)