The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity
- 270 Downloads
Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro.
KeywordsPaclitaxel Cisplatin Salicylic acid Neurotoxicity Antioxidant capacity Oxidative stress
This work supported by the Scientific & Technological Research Council of Turkey (TÜBİTAK, Project Number: 107S067).
Conflict of interest
The authors declared that there are no conflicts of interest.
- Chen C, Bai X, Bi Y, Liu G, Li H, Liu Z, Liu H (2015) Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro. Nutr Neurosci. doi: 10.1179/1476830514Y.0000000147
- Chentanez V, Thanomsridejchai N, Duangmardphon N, Agthong S, Kaewsema A, Huanmanop T, Maneesri S (2009) Ganglioside GM1 (porcine) ameliorates paclitaxel-induced neuropathy in rats. J Med Assoc Thai 92:50–57Google Scholar
- Daikhin Y, Yudkoff M (2000) Compartmentation of brain glutamate metabolism in neurons and glia. J Nutr 130:1026–1031Google Scholar
- Gören B, Mimbay Z, Bilici N, Zarifoğlu M, Oğul E, Korfali E (2009) Investigation of neuroprotective effects of cyclooxygenase inhibitors in the 6-hydroxydopamine induced rat Parkinson model. Turk Neurosurg 19:230–236Google Scholar
- Kusano C, Ferrari B (2008) Total antioxidant capacity: a biomarker in biomedical and nutritional studies. J Cell Mol Biol 7:1–15Google Scholar
- Openshaw H, Beamon K, Synold TW, Longmate J, Slatkin NE, Doroshow JH, Forman S, Margolin K, Morgan R, Shibata S, Somlo G (2004) Neurophysiological study of peripheral neuropathy after high-dose Paclitaxel: lack of neuroprotective effect of amifostine. Clin Cancer Res 10:461–467CrossRefGoogle Scholar
- Pisano C, Pratesi G, Laccabue D, Zunino F, Lo Giudice P, Bellucci A, Pacifici L, Camerini B, Vesci L, Castorina M, Cicuzza S, Tredici G, Marmiroli P, Nicolini G, Galbiati S, Calvani M, Carminati P, Cavaletti G (2003) Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of acetyl-l-carnitine. Clin Cancer Res 9:5756–5767Google Scholar
- Rispoli V, Rotiroti D, Carelli V, Liberatore F, Scipione L, Marra R, Giorgioni G, Di Stefano A (2004) Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert. Neurosci Lett 356:199–202CrossRefGoogle Scholar
- Togar B, Turkez H, Tatar A, Hacimuftuoglu A, Geyikoglu F (2014) Cytotoxicity and genotoxicity of zingiberene on different neuron cell lines in vitro. Cytotechnology. doi: 10.1007/s10616-014-9729-9
- Turkez H, Tatar A, Hacimuftuoglu A, Ozdemir E (2010) Boric acid as a protector against paclitaxel genotoxicity. Acta Biochim Pol 57:95–97Google Scholar
- Turkez H, Geyikoglu F, Yousef MI, Celik K, Bakir TO (2012a) Ameliorative effect of supplementation with l-glutamine on oxidative stress, DNA damage, cell viability and hepatotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat hepatocyte cultures. Cytotechnology 64:687–699CrossRefGoogle Scholar
- Zhang H, Mizumachi T, Carcel-Trullols J, Li L, Naito A, Spencer HJ, Spring PM, Smoller BR, Watson AJ, Margison GP, Higuchi M, Fan CY (2007) Targeting human 8-oxoguanine DNA glycosylase (hOGG1) to mitochondria enhances cisplatin cytotoxicity in hepatoma cells. Carcinogenesis 28:1629–1637CrossRefGoogle Scholar