Objective: To analyze the effect of curcumin and vitamin E on kidney function and inflammatory response of Wistar strain rats that received cisplatin. Material & Methods: An experimental laboratory study with a post-test only control design, using male Wistar strain rats (Rattus norwegicus). Rats were randomized using the simple randomized sampling method. Samples were treated with cisplatin 5 mg/kg (positive control group), vitamin E 100 mg/kg, curcumin 100 mg/kg body, and a combination of both (treatment group), to evaluate its effect on and kidney function and inflammatory response as measured by tumor necrosis factor-α (TNF-α), blood urea nitrogen (BUN) and serum creatinine. Results: There were differences in TNF-α levels in the positive control group (cisplatin 5 mg/kg) against each treatment group (p<0.05). Further analysis showed that there was a significant difference between the treatment group that received vitamin E and curcumin from the treatment group that received a combination of both (P<0.05). In addition, there were differences in BUN and serum creatinine levels in the positive control group (cisplatin 5 mg/kg) against each treatment group (p<0.05). However, there was no significant difference in BUN levels in the treatment group that received vitamin E with the treatment group that received curcumin or a combination of both (p>0.05). No differences were found in serum creatinine levels between treatment groups receiving vitamin E, curcumin, or a combination of both. Conclusion: Vitamin E 100 mg/kg, curcumin 100 mg/kg, and the combination of both have a nephroprotector feature in Wistar rats exposed to cisplatin.
Blood urea nitrogen, cisplatin, curcumin, nephroprotector, serum creatinine, TNF-α, vitamin E
Cheung WWL, Leung C, Wong MCS, Fung FDH, Ng CF, Goggins WB. The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection. Sci Rep. 2018; 8(1): 1–12.
Grossman HB, Lotan Y, Shariat S, Karakiewicz P, Kiemeney LA, Kassouf W, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol. 2012; 63(2): 234–41.
Ploeg M, Aben KKH, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009; 27(3): 289–93.
Moon E.-K, Park H.J, Oh C.-M, Jung K.W, Shin H.Y, Park B.K, Won Y.J. 2014. Cancer Incidence and Survival among Adolescents and Young Adults in Korea. PLoS One 9. 2014; 9(5): e96088.
Wang D, Lippard S.J. Cellular processing of platinum anticancer drugs. Nat. Rev. Drug Discov. 2005; 4: 307–320.
Perše M, Večerić-Haler Ž. Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges. Biomed Res. Int. 2018; 1–29.
Rosenberg B, Charles F, Kettring P. Fundamental studies with cisplatin. Cancer. 1985; 55: 2303–2316.
Darwish M.A, Abo-Youssef A.M, Khalaf M.M, Abo-Saif A.A, Saleh I.G, Abdelghany T.M. Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation. 2017; 31(1): 1-9.
Pabla N, Dong Z. Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int. 2008; 73: 994–1007.
Arany I, Safirstein R.L. Cisplatin nephrotoxicity. Semin. Nephrol. 2003; 23: 460–464.
Arunkumar P, Viswanatha G, Radheshyam N, Mukund H, Belliyappa M. Science behind cisplatin-induced nephrotoxicity in humans: a clinical study. 2012; 1691(12): 60112-9.
Hosten A.O. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition, in: Walker HK, Hall WD, H.J. (Ed.), Clinical Methods, 3rd edition The History, Physical, and Laboratory Examinations. Butterworths, Boston; 1990. p. 875.
Dillioglugil M.O, Maral Kir H, Gulkac M.D, Özon Kanli A, Ozdogan H.K, Acar O, Dillioglugil O. Protective Effects of Increasing Vitamin E and A Doses on Cisplatin-Induced Oxidative Damage to Kidney Tissue in Rats. Urol. Int. 2005; 75: 340–344.
Weijl N.I, Wipkink-Bakker A, Lentjes E.G.W.M, Berger H.M, Cleton F.J, Osanto S. Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Ann. Oncol. 1998; 9: 1331–1337.
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin Nephrotoxicity. 2010; 2: 2490–518.
Uzunhisarcikli M, Kalender Y. Protective effects of vitamins C and E against hepatotoxicity induced by methyl parathion in rats. Ecotoxicol. Environ. Saf. 2011; 74: 2112–2118.
Nematbakhsh M, Hamid N. The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based chemotherapy: A randomized, placebo-controlled study. Journal of research in medical sciences. 2013; 18(7): 626-627.
Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008; 75: 787–809.
Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005; 41: 1955–68.
Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti- inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009; 41: 40–59.
Kuhad, A. et al. Effect of Curcumin on Inflammation and Oxidative Stress in Cisplatin-Induced Experimental Nephrotoxicity. Journal of Agricultural and Food Chemistry. 2007; 55(25): 10150–10155.
Dahlan MS. Statistik untuk kedokteran dan kesehatan: uji hipotesis. Jakarta: Bina Mitra Press; 2006.
Kunze D, Erdmann K, Froehner M, Wirth MP, Fuessel S. siRNA-mediated Inhibition of Antiapoptotic Genes Enhances Chemotherapy Efficacy in Bladder Cancer Cells. 2012; 4318: 4313–8.
Manohar S, Leung N. Cisplatin nephrotoxicity : a review of the literature. J Nephrol. 2018; 31(1): 15-25.
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.
Ramesh G, Reeves WB. p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice. American Journal of Physiology-Renal Physiology. 2005; 289(1): F166-F174.
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.
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. 2019; 9: 1–14.
Combs, Gerald F., and James P. McClung. The Vitamins: Fundamental Aspects in Nutrition and Health. Amsterdam: Elsevier ; Academic Press; 2017.
Verma, A. Vitamin E Neuroprotection for Cisplatin Neuropathy: A Randomized, Placebo-controlled Trial. Yearbook of Neurology and Neurosurgery; 2010. p. 137-38.
Kalkanis, James G., Craig Whitworth, and Leonard P. Rybak. Vitamin E Reduces Cisplatin Ototoxicity. The Laryngoscope. 2004; 114(3): 538-42.
Leonetti C, Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol. 2003; 21(5): 927‐931.
Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research [published correction appears in Altern Med Rev. Altern Med Rev. 2009; 14(2): 141‐153.
Ali BH, Al-Salam S, Al Suleimani Y, Al Kalbani J, Al Bahlani S, Ashique M, et al. Curcumin Ameliorates Kidney Function and Oxidative Stress in Experimental Chronic Kidney Disease. Basic Clin Pharmacol Toxicol. 2018 Jan; 122(1): 65–73.
Dhima I, Zerikiotis S, Lekkas P, Simos Y V, Gkiouli M, Vezyraki P, et al. Curcumin Acts as a Chemosensitizer for Leiomyosarcoma Cells In Vitro But Fails to Mediate Antioxidant Enzyme Activity in Cisplatin-Induced Experimental Nephrotoxicity in Rats. Integr Cancer Ther. 2019; 18: 1534735419872811.
Ridzuan NRA, Rashid NA, Othman F, Budin SB, Hussan F, Teoh SL. Protective Role of Natural Products in Cisplatin-Induced Nephrotoxicity. Mini Rev Med Chem. 2019; 19(14): 1134–43.
Ozkok A, Edelstein CL. Pathophysiology of Cisplatin-Induced Acute Kidney Injury. 2014; 2014: 967826.
Shaloam D, Paul BT. Cisplatin in cancer therapy : molecular mechanisms of action. 2015; 0: 364–78.
Tebano MT, Carlini P, Loizzo A, Luzi M, Petrucci F, Alimonti A, Caroli S. Clinical pharmacokinetics of cumulative very high dose of cisplatin in chemotherapy resistant solid tumors. Annali dell’Istituto superiore di sanita. 1995; 31(3): 351-357.
Tsang, RY, Al-Fayea T, Au HJ. Cisplatin overdose: toxicities and management. Drug safety. 2009; 32(12): 1109–1122.
Siddik ZH. Mechanisms of Action of Cancer Chemotherapeutic Agents : DNA-Interactive Alkylating Agents and Antitumour Platinum-Based Drugs. John Wiley & Sons, Ltd; 2002.
Kim JY, Do YR, Park KU, et al. A multi-center phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer. Cancer Chemother Pharmacol. 2010; 66(1): 31‐36.
Ueki M, Ueno M, Morishita J, Maekawa N. Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice. J Biosci Bioeng. 2013; 115(5): 547–51.
Darwish MA, Saleh IG, Abo-youssef AM, Abdelghany TM, Khalaf MM, Abo-saif AA. Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation. 2016; (May): 1–9.
Venkatanarayana G, Sudhakara G, Sivajyothi P, Indira P. Protective effects of curcumin and vitamin E on carbon tetrachloride-induced nephrotoxicity in rats. EXCLI J. 2012; 11: 641–50.
Poston HA, Combs GF, Leibovitz L. Vitamin E and Selenium Interrelations in the Diet of Atlantic Salmon (Salmo salar): Gross, Histological and Biochemical Deficiency Signs. J Nutr. 1976; 106(7): 892–904.
Nisr RB, Shah DS, Ganley IG, Hundal HS. Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading. Cell Mol Life Sci. 2019; 76(24): 4887–904.
Subudhi U, Das K, Paital B, Bhanja S, Chainy GBN. Supplementation of curcumin and vitamin E enhances oxidative stress, but restores hepatic histoarchitecture in hypothyroid rats. Life Sci. 2009; 84(11–12): 372–9.
Soyalıç H, Gevrek F, Koç S, Avcu M, Metin M, Aladağ İ. Intraperitoneal curcumin and vitamin E combination for the treatment of cisplatin-induced ototoxicity in rats. Int J Pediatr Otorhinolaryngol. 2016; 89(2016): 173–8.
Hummel M, Kurian SM, Lin S, Borodyanskiy A, Zhang Z, Li Z, et al. Intragraft TNF receptor signaling contributes to activation of innate and adaptive immunity in a renal allograft model. Transplantation. 2009; 87(2): 178–88.
Zelová H, Hošek J. TNF-α signalling and inflammation: Interactions between old acquaintances. Inflamm Res. 2013; 62(7): 641–51.