Evaluation of Cisplatin Neurotoxicity in Cultured Rat Dorsal Root Ganglia via Cytosolic Calcium Accumulation

Year 2016, Volume: 33 Issue: 2, 0 - 0, 01.03.2016

Kevser Erol Semra Yiğitaslan Çiğdem Ünel Bilgin Kaygısız Engin Yıldırım

Abstract

Background: Calcium homeostasis is considered to be important in antineoplastic as well as in neurotoxic adverse effects of cisplatin.  Aims: This study aimed to investigate the role of Ca2+ in cisplatin neurotoxicity in cultured rat dorsal root ganglia (DRG) cells.  Study Design: Cell culture study. Methods: DRG cells prepared from 1-day old Sprague-Dawley rats were used to determine the role of Ca2+ in the cisplatin (10-600 μM) neurotoxicity. The cells were incubated with cisplatin plus nimodipine (1-3 μM), dizocilpine (MK-801) (1-3 μM) or thapsigargin (100-300 nM). Toxicity of cisplatinon DRG cells was determined by the MTT assay.  Results: The neurotoxicity of cisplatin was significant when used in high concentrations (100-600 μM). Nimodipine (1 μM) but not MK-801 or thapsigargin prevented the neurotoxic effects of 200 μM of cisplatin.  Conclusion: Voltage-dependent calcium channels may play a role in cisplatin neurotoxicity.

Keywords

Calcium, cisplatin, dorsal root ganglia, primary cell culture

References

• 1. Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst 2008;13:27-46. [CrossRef]
• 2. Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C. Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer 2008;44:1507-15. [CrossRef]
• 3. von Schlippe M, Fowler CJ, Harland SJ. Cisplatin neurotoxicity in the treatment of metastatic germ cell tumour: time course and prognosis. Br J Cancer 2001;85:823-6. [CrossRef]
• 4. Wu F, Lin X, Okuda T, Howell SB. DNA polymerase zeta regulates cisplatin cytotoxicity, mutagenicity, and the rate of development of cisplatin resistance. Cancer Res 2004;64:8029- 35. [CrossRef]
• 5. McDonald ES, Randon KR, Knight A, Windebank AJ. Cisplatin preferentially binds to DNA in dorsal root ganglion neurons in vitro and in vivo: a potential mechanism for neurotoxicity. Neurobiol Dis 2005;18:305-13. [CrossRef]