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Drug Res (Stuttg) 2019; 69(02): 75-82
DOI: 10.1055/a-0641-5148
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Pre-Treatment with Curcumin Ameliorates Cisplatin-Induced Kidney Damage by Suppressing Kidney Inflammation and Apoptosis in Rats

Vivian Soetikno
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Shinta Dewi Permata Sari
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Lulu Ul Maknun
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Nielda Kezia Sumbung
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Deliana Nur Ihsani Rahmi
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Bashar Adi Wahyu Pandhita
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Melva Louisa
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
,
Ari Estuningtyas
1   Department of Pharmacology and Therapeutic, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
› Author Affiliations
Further Information

Publication History

received 13 April 2018

accepted 06 June 2018

Publication Date:
26 June 2018 (online)

Also available at
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Abstract

Objective In addition to oxidative stress, inflammation and apoptosis have an important role in the pathogenesis of cisplatin-induced kidney damage. This study aimed to investigate the molecular mechanisms of protective effects of curcumin against cisplatin-induced kidney inflammation and apoptosis in rats.

Materials and Methods Eighteen rats were equally divided into three groups; normal (0.5% CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups. Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week before giving a single dose of cisplatin. Kidney and plasma were taken for analysis.

Results Cisplatin challenged rats demonstrated kidney injury as shown by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and kidney MDA, decreased of kidney GSH levels, and kidney histopathology alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-κB expression, which subsequently increased mRNA expression of TNF-α, IL-6, KIM-1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in kidney tissues. Pre-treatment with curcumin significantly ameliorated inflammation and apoptosis induced by cisplatin. In addition, curcumin downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group. Histopathological examination furthers confirmed the kidney damage protection effect of curcumin.

Conclusions These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration.

Key words

apoptosis - inflammation - renal pharmacology
 

  • References

  • 1 Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 2008; 73: 994-1007
    CrossrefPubMedGoogle Scholar
  • 2 Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol 2003; 23: 460-464
    CrossrefPubMedGoogle Scholar
  • 3 Jiang M, Dong Z. Regulation and pathological role of p53 in cisplatin nephrotoxicity. J Pharmacol Exp Ther 2008; 327: 300-307
    CrossrefPubMedGoogle Scholar
  • 4 Kuhlmann MK, Burkhardt G, Köhler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant 1997; 12: 2478-2480
    CrossrefPubMedGoogle Scholar
  • 5 Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410: 37-40
    CrossrefPubMedGoogle Scholar
  • 6 Prasaja Y, Sutandyo N, Andrajati R. Incidence of cisplatin-induced nephrotoxicity and associated factors among cancer patients in Indonesia. Asian Pac J Cancer Prev 2015; 16: 1117-1122
    CrossrefPubMedGoogle Scholar
  • 7 Ueki M, Ueno M, Morishita J. et al. Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice. J Biosci Bioeng 2013; 115: 547-551
    CrossrefPubMedGoogle Scholar
  • 8 Kuhad A, Pilkhwal S, Sharma S. et al. Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. J Agric Food Chem 2007; 55: 10150-10155
    CrossrefPubMedGoogle Scholar
  • 9 Topcu-Tarladacalisir Y, Sapmaz-Metin M, Karaca T. Curcumin counteracts cisplatin-induced nephrotoxicity by preventing renal tubular cell apoptosis. Ren Fail 2016; 38: 1741-1748
    CrossrefPubMedGoogle Scholar
  • 10 El-Naga RN. Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: Impact on NOX-1, inflammation and apoptosis. Toxicol Appl Pharmacol. 2014; 274: 87-95
    CrossrefPubMedGoogle Scholar
  • 11 Toora BD, Rajagopal G. Measurement of creatinine by Jaffe's reaction – determination of concentration of sodium hydroxide required for maximum color development in standard, urine and protein free filtrate of serum. Indian J Exp Biol 2002; 40: 352-354
    PubMedGoogle Scholar
  • 12 Bazzano T, Restel TI, Porfirio LC. et al. Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion. Acta Cir Bras 2015; 30: 277-288
    CrossrefPubMedGoogle Scholar
  • 13 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-408
    CrossrefPubMedGoogle Scholar
  • 14 Mohan IK, Khan M, Shobha JC. et al. Protection against cisplatin-induced nephrotoxicity by Spirulina in rats. Cancer Chemother Pharmacol 2006; 58: 802-808
    CrossrefPubMedGoogle Scholar
  • 15 Kalpana C, Sudheer AR, Rajasekharan KN. et al. Comparative effects of curcumin and its synthetic analogue on tissue lipid peroxidation and antioxidant status during nicotine-induced toxicity. Singapore Med J. 2007; 48: 124-130
    PubMedGoogle Scholar
  • 16 Ugur S, Ulu R, Dogukan A. et al. The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity. Ren Fail 2015; 37: 332-336
    PubMedGoogle Scholar
  • 17 Cetin R, Devrim E, Kiliçoğlu B. et al. Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods. J Appl Toxicol 2006; 26: 42-46
    CrossrefPubMedGoogle Scholar
  • 18 Agarwal R, Goel SK, Behari JR. Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercury. J Appl Toxicol 2010; 30: 457-468
    PubMedGoogle Scholar
  • 19 Ulu R, Arslan O, Dogukan A. et al. Effects of curcumin on anion/cation transporters and multidrug response proteins in cisplatin induced nephrotoxicity. Int J Clin Exp Med 2016; 9: 19623-19633
    PubMedGoogle Scholar
  • 20 Pabla N, Murphy RF, Liu K. et al. The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol 2009; 296: F505-F511
    CrossrefPubMedGoogle Scholar
  • 21 Ciarimboli G, Deuster D, Knief A. et al. Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions. Am J Pathol 2010; 176: 1169-1180
    CrossrefPubMedGoogle Scholar
  • 22 Sprowl JA, van Doorn L, Hu S. et al. Conjunctive therapy of cisplatin with the OCT2 inhibitor cimetidine: Influence on antitumor efficacy and systemic clearance. Clin Pharmacol Ther. 2013; 94: 585-592
    PubMedGoogle Scholar
  • 23 Arany I, Megyesi JK, Kaneto H. et al. Activation of ERK or inhibition of JNK ameliorates H(2)O(2) cytotoxicity in mouse renal proximal tubule cells. Kidney Int 2004; 65: 1231-1239
    CrossrefPubMedGoogle Scholar
  • 24 Kohda Y, Hiramatsu J, Gemba M. Involvement of MEK/ERK pathway in cephaloridine-induced injury in rat renal cortical slices. Toxicol Lett 2003; 143: 185-194
    CrossrefPubMedGoogle Scholar
  • 25 Jo SK, Cho WY, Sung SA. et al. MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis. Kidney Int 2005; 67: 458-466
    CrossrefPubMedGoogle Scholar
  • 26 Rubinfeld H, Seger R. The ERK cascade: A prototype of MAPK signaling. Mol Biotechnol 2005; 31: 151-174
    CrossrefPubMedGoogle Scholar
  • 27 Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene 2007; 26: 3100-3112
    CrossrefPubMedGoogle Scholar
  • 28 Keshet Y, Seger R. The MAP kinase signaling cascades: A system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 2010; 661: 3-38
    PubMedGoogle Scholar
  • 29 Kim YK, Kim HJ, Kwon CH. et al. Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol 2005; 25: 374-382
    CrossrefPubMedGoogle Scholar
  • 30 Park BG, Yoo CI, Kim HT. et al. Role of mitogen-activated protein kinases in hydrogen peroxide-induced cell death in osteoblastic cells. Toxicology 2005; 215: 115-125
    CrossrefPubMedGoogle Scholar
  • 31 Omar HA, Mohamed WR, Arab HH. et al. Tangeretin alleviates cisplatin-induced acute hepatic injury in rats: Targeting MAPKs and apoptosis. PLoS One 2016; 11: e0151649
    CrossrefPubMedGoogle Scholar
  • 32 Wada Y, Iyoda M, Matsumoto K. et al. Epidermal growth factor receptor inhibition with erlotinib partially prevents cisplatin-induced nephrotoxicity in rats. PLoS One 2014; 9: e111728
    CrossrefPubMedGoogle Scholar
  • 33 Humanes B, Lazaro A, Camano S. et al. Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats. Kidney Int 2012; 82: 652-663
    CrossrefPubMedGoogle Scholar
  • 34 Kang KP, Kim DH, Jung YJ. et al. Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation. Nephrol Dial Transplant 2009; 24: 3012-3020
    CrossrefPubMedGoogle Scholar
  • 35 Kim MG, Yang HN, Kim HW. et al. IL-10 mediates rosiglitazone-induced kidney protection in cisplatin nephrotoxicity. J Korean Med Sci 2010; 25: 557-563
    CrossrefPubMedGoogle Scholar
  • 36 Deng J, Kohda Y, Chiao H. et al. Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 2001; 60: 2118-2128
    CrossrefPubMedGoogle Scholar
  • 37 Ozer JS, Dieterle F, Troth S. et al. A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol 2010; 28: 486-494
    CrossrefPubMedGoogle Scholar
  • 38 Sinha V, Vence LM, Salahudeen AK. Urinary tubular protein-based biomarkers in the rodent model of cisplatin nephrotoxicity: A comparative analysis of serum creatinine, renal histology, and urinary KIM-1, NGAL, and NAG in the initiation, maintenance, and recovery phases of acute kidney injury. J Investig Med 2013; 61: 564-568
    CrossrefPubMedGoogle Scholar
  • 39 Sasaki D, Yamada A, Umeno H. et al. Comparison of the course of biomarker changes and kidney injury in a rat model of drug-induced acute kidney injury. Biomarkers 2011; 16: 553-566
    CrossrefPubMedGoogle Scholar
  • 40 Sabbisetti VS, Waikar SS, Antoine DJ. et al. Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol 2014; 25: 2177-2186
    CrossrefPubMedGoogle Scholar