EFFECTS OF CURCUMIN AND NANOCURCUMIN ON CISPLATIN-INDUCED NEPHROTOXICITY IN RAT: COPPER TRANSPORTER 1 AND ORGANIC CATION TRANSPORTER 2 AS DRUG TRANSPORTERS

Authors

  • Deliana Nur Ihsani Rahmi Department of Biomedical Science Postgraduate Program, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.
  • Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.
  • Vivian Soetikno Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.

DOI:

https://doi.org/10.22159/ijap.2018.v10s1.37

Keywords:

Cisplatin nephrotoxicity, Copper transporter 1, Curcumin, nanocurcumin, Organic cation transporter

Abstract

Objective: This study aimed to investigate the efficacy of curcumin (CMN) and nanocurcumin (NC) at preventing cisplatin (CDPP)-induced
nephrotoxicity.
Methods: Two membrane transporters, copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2), have been identified involved in active
accumulation of CDPP into renal tubular cells. We analyzed OCT2 transcription levels in rat kidney tissue and determined whether renoprotective
mechanism of CMN involves CTR1. Rats were randomly divided into five groups: (1) Control, (2) CDPP (7 mg/kg as single dose (i.p.), (3) CDPP+CMN
(7 mg/kg CDPP as a single dose, i.p.+100 mg/kg/day of CMN), (4) CDPP+50 mg NC (7 mg/kg CDPP as single dose, i.p.+50 mg/kg/day NC), and
(5) CDPP+100 mg NC (7 mg/kg CDPP as single dose, i.p.+100 mg/kg/day NC). Quantitative reverse transcription-polymerase chain reaction was
performed to calculate relative expression of CTR1 and OCT2 genes in rat kidney.
Results: Expression of CTR1 was unassociated with administration of CMN or NC, indicating CTR1 is uninvolved in renoprotective mechanism of CMN.
The administration of 100 mg/kg/day NC increased expression of OCT2; this increase was higher compared with normal expression levels. This may
be due to another regulatory mechanism from the CMN itself.
Conclusion: NC has a better renoprotective effect compared with curcumin, suggested by the increased OCT2 expression on its administration in
CDPP-treated rats.

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References

Dasari S, Tchounwou PB. Cisplatin in cancer therapy: Molecular

mechanisms of action. Eur J Pharm 2014;740:364-78.

Sushma M, Prasad KV, Jhansi LB, Vijay R, Uma MR. Prophylactic and

curative effect of ethanolic extract of Bassia malabarica bark against

cisplatin induced nephrotoxicity. Asian J Pharm Clin Res 2014;7:143-6.

Sreedevi A. Alleviation of cisplatin induced nephrotoxicity in albino

rats by roots Catunaregam uliginosa. Asian J Pharm Clin Res

;9:147‑51.

Pabla N, Dong Z. Cisplatin nephrotoxicity: Mechanisms and

renoprotective strategies. Kidney Int 2008;73:994-1007.

Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol

;23:460-4.

Burger H, Loos WJ, Eechoute K, Verweij J, Mathijssen RH, Wiemer EA,

et al. Drug transporters of platinum-based anticancer agents and their

clinical significance. Drug Resist Updat 2011;14:22-34.

Pabla N, Murphy RF, Liu K, Dong Z. The copper transporter Ctr1

contributes to cisplatin uptake by renal tubular cells during cisplatin

nephrotoxicity. J Physiol Renal Physiol 2008;296:F505-11.

Ciarimboli G, Ludwig T, Lang D, Pavenstädt H, Koepsell H,

Piechota HJ, et al. Cisplatin nephrotoxicity is critically mediated via

the human organic cation transporter 2. Am J Pathol 2005;167:1477-84.

Rezaee R, Momtazi AA, Monemi A, Sahebkar A. Curcumin:

A potentially powerful tool to reverse cisplatin-induced toxicity. Pharm

Res 2017;117:218-27.

Steffi PF, Srinivasan M. Curcumin, a potent anticarcinogenic

polyphenol – A review. Asian J Pharm Clin Res 2014;7 Suppl.2:10-8.

Shankar TN, Shantha NV, Ramesh HP, Murthy IA, Murthy VS. Toxicity

studies on turmeric (Curcuma longa): Acute toxicity studies in rats,

guineapigs and monkeys. Indian J Exp Biol 1980;18:73-5.

Qureshi S, Shah AH, Ageel AM. Toxicity studies on Alpinia galanga

and Curcuma longa. Planta Med 1992;58:124-7.

Lao CD, Demierre MF, Sondak VK. Targeting events in melanoma

carcinogenesis for the prevention of melanoma. Expert Rev Anticancer

Ther 2006;6:1559-68.

Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM,

et al. Dose escalation of a curcuminoid formulation. BMC Complement

Altern Med 2006;6:10.

Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I

clinical trial of curcumin, a chemopreventive agent, in patients with

high-risk or pre-malignant lesions. Anticancer Res 2001;21:2895-900.

Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS, et al.

Influence of piperine on the pharmacokinetics of curcumin in animals

and human volunteers. Planta Med 1998;64:353-6.

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB.

Bioavailability of curcumin: Problems and promises. Mol Pharm

;4:807-18.

Yallapu MM, Jaggi M, Chauhan SC. Curcumin nanoformulations:

A future nanomedicine for cancer. Drug Discov Today 2012;17:71-80.

Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of

cisplatin nephrotoxicity. Toxins (Basel) 2010;2:2490-518.

Aleksunes LM, Augustine LM, Scheffer GL, Cherrington NJ,

Manautou JE. Renal xenobiotic transporters are differentially expressed

in mice following cisplatin treatment. Toxicology 2008;250:82-8.

Published

20-12-2018

How to Cite

Rahmi, D. N. I., Louisa, M., & Soetikno, V. (2018). EFFECTS OF CURCUMIN AND NANOCURCUMIN ON CISPLATIN-INDUCED NEPHROTOXICITY IN RAT: COPPER TRANSPORTER 1 AND ORGANIC CATION TRANSPORTER 2 AS DRUG TRANSPORTERS. International Journal of Applied Pharmaceutics, 10(1), 172–174. https://doi.org/10.22159/ijap.2018.v10s1.37

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