Preventive effect of selenium pretreatment against cisplatin-induced oral mucositis in rats

Abstract

Objective. The aim of the present study was to investigate the protective role of selenium against cisplatin-induced oral mucositis in rats. Methods. Healthy wistar albino rats (n=21) were randomly divided into three groups: Cisplatin (Cis), cisplatin and selenium (Cis+Se) and control (C). Cisplatin was administered for 3 days to Cis and Cis+Se groups. Cis+Se group received selenium 5 days before cisplatin injection and continued for 11 consecutive days. Malondialdehyde (MDA) levels of the rats were determined before and at the end of experimental protocol. The tongues of rats were harvested for immunuhistochemical examinations. Results. In biochemichal analysis, MDA levels significantly increased in the Cis group (p=0.018). On the contrary, there was no significant difference between pretreatment and posttreatment MDA levels in Cis+Se group (p=0.128). In the immunohistochemical examinations of lingual tissues stained with anti-caspase-3, when the Cis and Cis+Se groups were compared, there were significantly more immunopositivity in the Cis group and significantly less immunopositivity in the Cis+Se group (p<0.05). Conclusions. Selenium might have played a protective role against cisplatin-induced oral mucositis in rats. Further studies are necessary before its clinical use in patients.

Keywords

• Cisplatin,oral mucositis; selenium; toxicity

References

1. [1] Sonis ST. Oral mucositis in head and neck cancer: risk, biology, and management. Am Soc Clin Oncol Educ Book 2013. doi: 10.1200/EdBook_AM.2013.33.e236.
2. [2] Nomura M, Kamata M, Kojima H, Hayashi K, Sawada S. Irsogladine maleate reduces the incidence of fluorouracil-based chemotherapy-induced oral mucositis. Ann Oncol 2013;24:1062- 66.
3. [3] Mortensen HR, Overgaard J, Specht L, Overgaard M, Johansen J, Evensen JF, et al. Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer. Radiother Oncol 2012;103:69-75.
4. [4] Kikkawa YS, Nakagawa T, Taniguchi M, Ito J. Hydrogen protects auditory hair cells from cisplatin-induced free radicals. Neurosci Lett 2014;579:125-9.
5. [5] Feghali JG, Liu W, Water TRVD. L-N-acetyl-cysteine protection against cisplatin induced auditory neuronal and hair cell toxicity. Laryngoscope 2001;111:1147-55.
6. [6] Rezvanfar MA, Rezvanfar MA, Shahverdi AR, Ahmadi A, Baeeri M, Mohammadirad A, et al. Protection of cisplatininduced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles. Toxicol Appl Pharmacol 2013;266:356-65.
7. [7] Ognjanovic BI, Djordjevic NZ, Matic MM, Obradovic JM, Mladenovic JM, Stajn AS, et al. Lipid peroxidative damage on cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium. Int J Mol Sci 2012;13:1790-803.
8. [8] Erken HA, Koc ER, Yazici H, Yay A, Onder GO, Sarici SF. Selenium partially prevents cisplatin-induced neurotoxicity: a preliminary study. Neurotoxicology 2014;42:71-5.

9. [9] Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453-61.
10. [10] Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 2007;109:820-31.
11. [11] Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004;100(9Suppl):1995-2025.
12. [12] Blijlevens N, Schwenkglenks M, Bacon P, Einsele H, D'Addio A, Maertens J, et al. Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy – European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol 2008;26:1519-25.
13. [13] Nicolatou-Galitis O, Sarri T, Bowen J, Di Palma M, Kouloulias VE, Niscola P, et al. Systematic review of antiinflammatory agents for the management of oral mucositis in cancer patients. Support Care Cancer 2013;21:3179-89.
14. [14] Nicolatou-Galitis O, Sarri T, Bowen J, Di Palma M, Kouloulias VE, Niscola P, et al. Systematic review of amifostine for the management of oral mucositis in cancer patients. Support Care Cancer 2013;21:357-64.
15. [15] Moslehi A, Taghizadeh-Ghehi M, Gholami K, Hadjibabaie M, Jahangard-Rafsanjani Z, Sarayani A, et al. N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a doubleblind, randomized, placebo-controlled trial. Bone Marrow Transplant 2014;49:818-23.
16. [16] Villa A, Sonis ST. Mucositis: pathobiology and management. Curr Opin Oncol 2015;27:159-64.
17. [17] Melo ML, Brito GA, Soares RC, Carvalho SB, Silva JV, Soares PM, et al. Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide. Cancer Chemother Pharmacol 2008;61:775-84.
18. [18] Van Ruijven MW, De Groot JC, Klis SF, Smoorenburg GF. The cochlear targets of cisplatin: an electrophysiological and morphological time-sequence study. Hear Res 2005;205:241-8.
19. [19] Salvesen GS, Duckett CS. IAP proteins: blocking the road to death's door. Nat Rev Mol Cell Biol 2002;3:401-10.
20. [20] Krieser RJ, Eastman A. Cleavage and nuclear translocation of the caspase 3 substrate Rho GDP-dissociation inhibitor, D4- GDI, during apoptosis. Cell Death Differ 1999;6:412-19.
21. [21] Kim SJ, Ho Hur J, Park C, Kim HJ, Oh GS, Lee JN, et al. Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes. Exp Mol Med 2015;47:e142.