Skip to main content
SpringerLink
Log in

The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity

  • Original Article
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aydın E, Türkez H, Keleş MS (2014) The effect of carvacrol on healthy neurons and N2a cancer cells: some biochemical, anticancerogenicity and genotoxicity studies. Cytotechnology 66:149–157

    Article  Google Scholar 

  • Barabas K, Milner R, Lurie D, Adin C (2008) Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol 6:1–18

    Article  CAS  Google Scholar 

  • Cacciatore I, Caccuri AM, Di Stefano A, Luisi G, Nalli M, Pinnen F, Ricci G, Sozio P (2003) Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage. Farmaco 58:787–793

    Article  CAS  Google Scholar 

  • Cacciatore I, Caccuri AM, Cocco A, De Maria F, Di Stefano A, Luisi G, Pinnen F, Ricci G, Sozio P, Turella P (2005) Potent isozyme-selective inhibition of human glutathione S-transferase A1-1 by a novel glutathione S-conjugate. Amino Acids 29:255–261

    Article  CAS  Google Scholar 

  • 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 92:50–57

    Google Scholar 

  • Cingolani GM, Di Stefano A, Mosciatti B, Napolitani F, Giorgioni G, Ricciutelli M, Claudi F (2000) Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as potential prodrug of L-dopa. Bioorg Med Chem Lett 10:1385–1388

    Article  CAS  Google Scholar 

  • Colak S, Geyikoǧlu F, Keles ON, Turkez H, Topal A, Unal B (2011) The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity. Toxicol Ind Health 27:700–710

    Article  CAS  Google Scholar 

  • Daikhin Y, Yudkoff M (2000) Compartmentation of brain glutamate metabolism in neurons and glia. J Nutr 130:1026–1031

    Google Scholar 

  • Dirican E, Turkez H (2014) In vitro studies on protective effect of Glycyrrhiza glabra root extracts against cadmium-induced genetic and oxidative damage in human lymphocytes. Cytotechnology 66:9–16

    Article  Google Scholar 

  • Di Stefano A, D’Aurizio E, Trubiani O, Grande R, Di Campli E, Di Giulio M, Di Bartolomeo S, Sozio P, Iannitelli A, Nostro A, Cellini L (2009) Viscoelastic properties of Staphylococcus aureus and Staphylococcus epidermidis mono-microbial biofilms. Microb Biotechnol 2:634–641

    Article  Google Scholar 

  • Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285

    Article  CAS  Google Scholar 

  • Feghali JG, Liu W, Van De Water TR (2001) L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 111:1147–1155

    Article  Google Scholar 

  • Ferger B, Teismann P, Earl CD, Kuschinsky K, Oertel WH (1999) Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice. Naunyn Schmiedebergs Arch Pharmacol 360:256–261

    Article  CAS  Google Scholar 

  • Geyikoglu F, Turkez H (2008) Boron compounds reduce vanadium tetraoxide genotoxicity in human lymphocytes. Environ Toxicol Pharmacol 26:342–347

    Article  CAS  Google 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 19:230–236

    Google Scholar 

  • Gornstein E, Schwarz TL (2014) The paradox of paclitaxel neurotoxicity: mechanisms and unanswered questions. Neuropharmacology 76:175–183

    Article  CAS  Google Scholar 

  • Hassan HA, Edrees GM, El-Gamel EM, El-Sayed EA (2014) Amelioration of cisplatin-induced nephrotoxicity by grape seed extract and fish oil is mediated by lowering oxidative stress and DNA damage. Cytotechnology 66:419–429

    Article  CAS  Google Scholar 

  • Heuking S, Iannitelli A, Di Stefano A, Borchard G (2009) Toll-like receptor-2 agonist functionalized biopolymer for mucosal vaccination. Inter J Pharmaceut 381:97–105

    Article  CAS  Google Scholar 

  • Hospers GA, Eisenhauer EA, de Vries EG (1999) The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects. Br J Cancer 80:629–638

    Article  CAS  Google Scholar 

  • Huang GC, Liu SY, Lin MH, Kuo YY, Liu YC (2004) The synergistic cytotoxicity of cisplatin and taxol in killing oral squamous cell carcinoma. Jpn J Clin Oncol 34:499–504

    Article  Google Scholar 

  • Jekunen AP, Christen RD, Shalinsky DR, Howell SB (1994) Synergistic interaction between cisplatin and taxol in human ovarian-carcinoma cells in-vitro. Br J Cancer 69:299–306

    Article  CAS  Google Scholar 

  • Kamisli S, Ciftci O, Cetin A, Kaya K, Kamisli O, Celik H (2014) Fish oil protects the peripheral and central nervous systems against cisplatin-induced neurotoxicity. Nutr Neurosci 17:116–126

    Article  CAS  Google Scholar 

  • Karpińska A, Gromadzka G (2013) Oxidative stress and natural antioxidant mechanisms: the role in neurodegeneration. From molecular mechanisms to therapeutic strategies. Postepy Hig Med Dosw 6 67:43–53

    Article  Google Scholar 

  • Kusano C, Ferrari B (2008) Total antioxidant capacity: a biomarker in biomedical and nutritional studies. J Cell Mol Biol 7:1–15

    CAS  Google Scholar 

  • Mao-Ying QL, Kavelaars A, Krukowski K, Huo XJ, Zhou W, Price TJ, Cleeland C, Heijnen CJ (2014) The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model. PLoS One 9:e100701

    Article  Google Scholar 

  • Marupudi NI, Han JE, Li KW, Renard VM, Tyler BM, Brem H (2007) Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin Drug Saf 6:609–621

    Article  CAS  Google Scholar 

  • Minami SB, Sha SH, Schacht J (2004) Antioxidant protection in a new animal model of cisplatin-induced ototoxicity. Hear Res 198:137–143

    Article  CAS  Google Scholar 

  • Mohanakumar KP, Muralikrishnan D, Thomas B (2000) Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res 864:281–290

    Article  CAS  Google 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 10:461–467

    Article  CAS  Google 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 9:5756–5767

    CAS  Google Scholar 

  • Ramanathan B, Jan KY, Chen CH, Hour TC, Yu HJ, Pu YS (2005) Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res 65:8455–8460

    Article  CAS  Google Scholar 

  • Rick O, Beyer J, Schwella N, Schubart H, Schleicher J, Siegert W (2001) Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor. Ann Oncol 12:1151–1155

    Article  CAS  Google 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 356:199–202

    Article  CAS  Google Scholar 

  • Rivas-San Vicente M, Plasencia J (2011) Salicylic acid beyond defence: its role in plant growth and development. J Exp Bot 62:3321–3338

    Article  CAS  Google Scholar 

  • Rovini A, Carré M, Bordet T, Pruss RM, Braguer D (2010) Olesoxime prevents microtubule-targeting drug neurotoxicity: selective preservation of EB comets in differentiated neuronal cells. Biochem Pharmacol 80:884–894

    Article  CAS  Google Scholar 

  • Shabana YM, Abdel-Fattah GM, Ismail AE, Rashad YM (2008) Control of brown spot pathogen of rice (Bipolaris oryzae) using some phenolic antioxidants. Braz J Microbiol 39:438–444

    Article  CAS  Google Scholar 

  • Song W, Tang Z, Li M, Lv S, Sun H, Deng M, Liu H, Chen X (2014) Polypeptide-based combination of paclitaxel and cisplatin for enhanced chemotherapy efficacy and reduced side-effects. Acta Biomater 10:1392–1402

    Article  CAS  Google Scholar 

  • Sozio P, D’Aurizio E, Iannitelli A, Cataldi A, Zara S, Cantalamessa F, Nasuti C, Di Stefano A (2010) Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity. Arch Pharm 343:133–142

    Article  CAS  Google 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, Geyikoglu F (2011) The efficiacy of bismuth subnitrate against genotoxicity and oxidative stress induced by aluminum sulphate. Toxicol Ind Health 27:133–142

    Article  CAS  Google Scholar 

  • Turkez H, Tatar A, Hacimuftuoglu A, Ozdemir E (2010) Boric acid as a protector against paclitaxel genotoxicity. Acta Biochim Pol 57:95–97

    CAS  Google 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 64:687–699

    Article  CAS  Google Scholar 

  • Turkez H, Geyikoglu F, Mokhtar YI, Togar B (2012b) Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin- induced hepatic toxicity in cultured rat hepatocytes. Cytotechnology 64:15–25

    Article  CAS  Google Scholar 

  • Turkez H, Celik K, Toğar B (2014) Effects of copaene, a tricyclic sesquiterpene, on human lymphocytes cells in vitro. Cytotechnology 66:597–603

    Article  CAS  Google Scholar 

  • Van den Berg JH, Beijnen JH, Balm AJ, Schellens JH (2006) Future opportunities in preventing cisplatin induced ototoxicity. Cancer Treat Rev 32:390–397

    Article  Google Scholar 

  • Vlot AC, Dempsey DA, Klessig DF (2009) Salicylic acid, a multifaceted hormone to combat disease. Annu Rev Phytopathol 47:177–206

    Article  CAS  Google Scholar 

  • Wang Y, Wang M, Qi H, Pan P, Hou T, Li J, He G, Zhang H (2014) Pathway-dependent inhibition of paclitaxel hydroxylation by kinase inhibitors and assessment of drug-drug interaction potentials. Drug Metab Dispos 42:782–795

    Article  Google Scholar 

  • Xue LJ, Guo W, Yuan Y, Anino EO, Nyamdari B, Wilson MC, Frost CJ, Chen HY, Babst BA, Harding SA, Tsai CJ (2013) Constitutively elevated salicylic acid levels alter photosynthesis and oxidative state but not growth in transgenic populus. Plant Cell 25:2714–2730

    Article  CAS  Google 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 28:1629–1637

    Article  CAS  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

  1. Department of Medical Pharmacology, Faculty of Medicine, Kafkas University, Kars, Turkey

    Damla Cetin

  2. Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey

    Ahmet Hacımuftuoglu

  3. Department of Medical Genetics, Faculty of Medicine, Atatürk University, Erzurum, Turkey

    Abdulgani Tatar

  4. Department of Molecular Biology and Genetics, Faculty of Sciences, Erzurum Technical University, Erzurum, Turkey

    Hasan Turkez

  5. Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Chieti, Italy

    Hasan Turkez

  6. Department of Biology, Faculty of Science, Atatürk University, Erzurum, Turkey

    Basak Togar

Authors
  1. Damla Cetin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmet Hacımuftuoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdulgani Tatar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hasan Turkez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Basak Togar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmet Hacımuftuoglu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cetin, D., Hacımuftuoglu, A., Tatar, A. et al. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology 68, 1361–1367 (2016). https://doi.org/10.1007/s10616-015-9896-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-015-9896-3

Keywords

Search

Navigation