Published 2020-07-20
Eldien Muhammad Shidqy Doddy M. Soebadi Lukman Hakim


Objective: To analyze the protective effect of vitamin E on TNF-α levels in white Wistar strains exposed to Cisplatin. Material & Methods: The design of this study was an experimental laboratory with post-test only control group design, with the evaluation of TNF-α levels carried out after the animals were treated. The grouping of experimental animals was carried out by randomization. This study using male Wistar white rats as samples. The control group in this study included a negative control group (CN), which was given an injection of 1 cc intravenous normal saline 0.9% on the 7th day as a placebo, then on the 10th day the blood sample was taken. The positive control group (CP), which was given cisplatin treatment at a dose of 5 mg/kg intraperitoneally, once on the 7th day. Treatment group (P1) was treated using cisplatin 5 mg/kg intra-peritoneally and Vitamine E 100 mg/KgBW, and Treatment group (P2) was treated using cisplatin 5 mg/kg intra-peritoneally and Vitamine E 200 mg/KgBW. Blood samples were taken on the 10th day, intra-cardiac and TNF-α levels were analyzed using ELISA. Results: There were significant differences in the mean TNF-α levels in the negative control group for all treatment groups with a p-value <0.05. There was also a significant difference in TNF-α levels in the positive control group for treatment group 1 and treatment 2 with p<0.05. On the other hand, further analysis showed that there was no significant difference between treatment group 1 and treatment group 2 (p>0.05). Conclusion: TNF-α levels in mice given cisplatin was much higher compared with the control group. Vitamin E 100 and 200 mg/kgBW cause a decrease in TNF-α protein levels in mice injected with cisplatin when compared with controls. There is no difference in TNF-α levels in mice receiving vitamin E at doses of 100 and 200 mg/kgBW



vitamin E, Cisplatin, TNF-α


Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 v1.0. International Agency for Research on Cancer, editor. World Health Organization; 2013.

Fuertes M, Castilla J, Alonso C, Pérez J. Cisplatin Biochemical Mechanism of Action: From Cytotoxicity to Induction of Cell Death Through Interconnections Between Apoptotic and Necrotic Pathways. Curr Med Chem. 2012; 10(3): 257–66.

Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel). 2010; 2(11): 2490–518.

Nematbakhsh M, Nasri H. The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based chemotherapy: A randomized, placebo-controlled study. J Res Med Sci. 2013; 18(7): 626–7.

Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: An historical perspective and an update. Eur J Cancer. 1998; 34(10): 1522–34.

Kunze D, Wuttig D, Füssel S, Meye A, Wirth MP. Sirna-Mediated Inhibition of Antiapoptotic Genes in Human Bladder Cancer Cells. Eur Urol Suppl. 2006; 5(14): 800.

Zhang B, Ramesh G, Norbury CC, Reeves WB. Cisplatin-induced nephrotoxicity is mediated by tumor necrosis factor-α produced by renal parenchymal cells. Kidney Int. 2007; 72(1): 37–44.

Pabla N, Dong Z. Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int. 2008 May; 73(9): 994–1007.

Kumar P, Barua CC, Sulakhiya K, Sharma RK. Curcumin ameliorates cisplatin-induced nephrotoxicity and potentiates its anticancer activity in SD rats: Potential role of curcumin in breast cancer chemotherapy. Front Pharmacol. 2017; 8(APR): 1–12.

Liu M, Chien CC, Burne-Taney M, Molls RR, Racusen LC, Colvin RB, et al. A pathophysiologic role for T lymphocytes in murine acute cisplatin nephrotoxicity. J Am Soc Nephrol. 2006; 17(3): 765–74.

Volarevic V, Djokovic B, Jankovic MG, Harrell CR, Fellabaum C, Djonov V, et al. Molecular mechanisms of cisplatin-induced nephrotoxicity: A balance on the knife edge between renoprotection and tumor toxicity. J Biomed Sci. 2019; 26(1): 1–14.

Kosmidou I, Vassilakopoulos T, Xagorari A, Zakynthinos S, Papapetropoulos A, Roussos C. Production of interleukin-6 by skeletal myotubes: Role of reactive oxygen species. Am J Respir Cell Mol Biol. 2002; 26(5): 587–93.

Ramesh G, Reeves WB. TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest. 2002; 110(6): 835–42.

Combs GF, McClung JP. The Vitamins: Fundamental Aspects in Nutrition and Health. 5th ed. Academic Press, Inc., San Diego; 2017. 628 p.

Pace A, Giannarelli D, Galiè E, Savarese A, Carpano S, Della Giulia M, et al. Vitamin e neuroprotection for cisplatin neuropathy: A randomized, placebo-controlled trial. Neurology. 2010; 74(9): 762–6.

Kalkanis JG, Whitworth C, Rybak LP. Vitamin E Reduces Cisplatin Ototoxicity. Laryngoscope. 2004; 114(3): 538–42.

Mehany HA, Abo-youssef AM, Ahmed LA, Arafa E-SA, Abd El-Latif HA. Protective effect of vitamin E and atorvastatin against potassium dichromate-induced nephrotoxicity in rats. Beni-Suef Univ J Basic Appl Sci. 2013; 2(2): 96–102.

Roberts NJ, Zhou S, Diaz LA, Holdhoff M. Systemic use of tumor necrosis factor alpha as an anticancer agent. Oncotarget. 2011; 2(10): 739–51.

Rizvi S, Raza ST, Ahmed F, Ahmad A, Abbas S, Mahdi F. The role of Vitamin E in human health and some diseases. Sultan Qaboos Univ Med J. 2014; 14(2): 157–65.

Copyright Information
Department of Urology, Faculty of Medicine/Airlangga University