Original articles
Joseph L. Jilek, Kayla L. Frost, Kevyn A. Jacobus, Wenxi He, Erica L. Toth, Michael Goedken, Nathan J. Cherrington. Altered cisplatin pharmacokinetics during nonalcoholic steatohepatitis contributes to reduced nephrotoxicity[J]. Acta Pharmaceutica Sinica B, 2021, 11(12): 3869-3878

Altered cisplatin pharmacokinetics during nonalcoholic steatohepatitis contributes to reduced nephrotoxicity
Joseph L. Jileka, Kayla L. Frosta, Kevyn A. Jacobusa, Wenxi Hea, Erica L. Totha, Michael Goedkenb, Nathan J. Cherringtona
a. Department of Pharmacology & Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85724, USA;
b. Rutgers Translational Sciences, Rutgers University, Piscataway, NJ 08901, USA
Abstract:
Disease-mediated alterations to drug disposition constitute a significant source of adverse drug reactions. Cisplatin (CDDP) elicits nephrotoxicity due to exposure in proximal tubule cells during renal secretion. Alterations to renal drug transporter expression have been discovered during nonalcoholic steatohepatitis (NASH), however, associated changes to substrate toxicity is unknown. To test this, a methionine- and choline-deficient diet-induced rat model was used to evaluate NASH-associated changes to CDDP pharmacokinetics, transporter expression, and toxicity. NASH rats administered CDDP (6 mg/kg, i.p.) displayed 20% less nephrotoxicity than healthy rats. Likewise, CDDP renal clearance decreased in NASH rats from 7.39 to 3.83 mL/min, renal secretion decreased from 6.23 to 2.80 mL/min, and renal CDDP accumulation decreased by 15%, relative to healthy rats. Renal copper transporter-1 expression decreased, and organic cation transporter-2 and ATPase copper transporting protein-7b increased slightly, reducing CDDP secretion. Hepatic CDDP accumulation increased 250% in NASH rats relative to healthy rats. Hepatic organic cation transporter-1 induction and multidrug and toxin extrusion protein-1 and multidrug resistance-associated protein-4 reduction may contribute to hepatic CDDP sequestration in NASH rats, although no drug-related toxicity was observed. These data provide a link between NASH-induced hepatic and renal transporter expression changes and CDDP renal clearance, which may alter nephrotoxicity.
Key words:    Nonalcoholic steatohepatitis    NASH    Cisplatin    Drug transporter    Nephrotoxicity   
Received: 2020-12-16     Revised: 2021-03-09
DOI: 10.1016/j.apsb.2021.05.030
Funds: This work was supported by the National Institutes of Health (R01ES028668, P30ES006694, and T32ES007091, USA).
Corresponding author: Nathan J. Cherrington,E-mail:cherring@pharmacy.arizona.edu     Email:cherring@pharmacy.arizona.edu
Author description:
Service
PDF(KB) Free
Print
0
Authors
Joseph L. Jilek
Kayla L. Frost
Kevyn A. Jacobus
Wenxi He
Erica L. Toth
Michael Goedken
Nathan J. Cherrington

References:
[1] Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol 2008;6:1-18
[2] Ishida S, Lee J, Thiele DJ, Herskowitz I. Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl Acad Sci U S A 2002;99:14298-14302
[3] Filipski KK, Mathijssen RH, Mikkelsen TS, Schinkel AH, Sparreboom A. Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity. Clin Pharmacol Ther 2009;86:396-402
[4] Lin X, Okuda T, Holzer A, Howell SB. The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae. Mol Pharmacol 2002;62:1154-1159
[5] Townsend DM, Deng M, Zhang L, Lapus MG, Hanigan MH. Metabolism of cisplatin to a nephrotoxin in proximal tubule cells. J Am Soc Nephrol 2003;14:1-10
[6] Mitchell AE, Morin D, Lakritz J, Jones AD. Quantitative profiling of tissue- and gender-related expression of glutathione S-transferase isoenzymes in the mouse. Biochem J 1997;325:207-216
[7] Sadzuka Y, Shimizu Y, Takino Y, Hirota S. Protection against cisplatin-induced nephrotoxicity in the rat by inducers and an inhibitor of glutathione S-transferase. Biochem Pharmacol 1994;48:453-459
[8] Townsend DM, Tew KD, He L, King JB, Hanigan MH. Role of glutathione S-transferase Pi in cisplatin-induced nephrotoxicity. Biomed Pharmacother 2009;63:79-85
[9] Yonezawa A, Inui K. Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br J Pharmacol 2011;164:1817-1825
[10] Yonezawa A, Inui K. Organic cation transporter OCT/SLC22A and H+/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents. Biochem Pharmacol 2011;81:563-568
[11] Hamaguchi K, Godwin AK, Yakushiji M, O'Dwyer PJ, Ozols RF, Hamilton TC. Cross-resistance to diverse drugs is associated with primary cisplatin resistance in ovarian cancer cell lines. Cancer Res 1993;53:5225-5232
[12] Targher G, Bertolini L, Rodella S, Lippi G, Zoppini G, Chonchol M. Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol 2010;5:2166-2171
[13] Shah RR, Smith RL. Addressing phenoconversion: the Achilles' heel of personalized medicine. Br J Clin Pharmacol 2015;79:222-240
[14] Canet MJ, Hardwick RN, Lake AD, Dzierlenga AL, Clarke JD, Goedken MJ, Cherrington NJ. Renal xenobiotic transporter expression is altered in multiple experimental models of nonalcoholic steatohepatitis. Drug Metab Dispos 2015;43:266-272
[15] Clarke JD, Dzierlenga AL, Nelson NR, Li H, Werts S, Goedken MJ, Cherrington NJ. Mechanism of altered metformin distribution in nonalcoholic steatohepatitis. Diabetes 2015;64:3305-3313
[16] Laho T, Clarke JD, Dzierlenga AL, Li H, Klein DM, Goedken M, Micuda S, Cherrington NJ. Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir. Biochem Pharmacol 2016;115:144-151
[17] Canet MJ, Hardwick RN, Lake AD, Dzierlenga AL, Clarke JD, Cherrington NJ. Modeling human nonalcoholic steatohepatitis-associated changes in drug transporter expression using experimental rodent models. Drug Metab Dispos 2014;42:586-595
[18] Thakkar N, Slizgi JR, Brouwer KLR. Effect of liver disease on hepatic transporter expression and function. J Pharm Sci 2017;106:2282-2294
[19] Oda M, Koyanagi S, Tsurudome Y, Kanemitsu T, Matsunaga N, Ohdo S. Renal circadian clock regulates the dosing-time dependency of cisplatin-induced nephrotoxicity in mice. Mol Pharmacol 2014;85:715-722
[20] Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW. Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. J Pharmacol Exp Ther 1980;213:551-556
[21] Shaik AN, Altomare DA, Lesko LJ, Trame MN. Development and validation of a LC-MS/MS assay for quantification of cisplatin in rat plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci 2017;1046:243-249
[22] Turner ME, Laverty KJ, Jeronimo PS, Kaufmann M, Jones G, White CA, Holden RM, Adams MA. Validation of a routine two-sample iohexol plasma clearance assessment of GFR and an evaluation of common endogenous markers in a rat model of CKD. Physiol Rep 2017;5:e13205
[23] Siddik ZH, Newell DR, Boxall FE, Harrap KR. The comparative pharmacokinetics of carboplatin and cisplatin in mice and rats. Biochem Pharmacol 1987;36:1925-1932
[24] Hanada K, Ninomiya K, Ogata H. Pharmacokinetics and toxicodynamics of cisplatin and its metabolites in rats: relationship between renal handling and nephrotoxicity of cisplatin. J Pharm Pharmacol 2000;52:1345-1353
[25] Campbell AB, Kalman SM, Jacobs C. Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity. Cancer Treat Rep 1983;67:169-172
[26] Perse M, Veceric-Haler Z. Cisplatin-induced rodent model of kidney injury: characteristics and challenges. Biomed Res Int 2018;2018:1462802
[27] Filipski KK, Loos WJ, Verweij J, Sparreboom A. Interaction of Cisplatin with the human organic cation transporter 2. Clin Cancer Res 2008;14:3875-3880
[28] Liang ZD, Stockton D, Savaraj N, Tien Kuo M. Mechanistic comparison of human high-affinity copper transporter 1-mediated transport between copper ion and cisplatin. Mol Pharmacol 2009;76:843-853
[29] Sprowl JA, Ciarimboli G, Lancaster CS, Giovinazzo H, Gibson AA, Du G, Janke LJ, Cavaletti G, Shields AF, Sparreboom A. Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2. Proc Natl Acad Sci U S A 2013;110:11199-11204
[30] Safaei R, Otani S, Larson BJ, Rasmussen ML, Howell SB. Transport of cisplatin by the copper efflux transporter ATP7B. Mol Pharmacol 2008;73:461-468
[31] Komatsu M, Sumizawa T, Mutoh M, Chen ZS, Terada K, Furukawa T, Yang XL, Gao H, Miura N, Sugiyama T, Akiyama S. Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance. Cancer Res 2000;60:1312-1316
[32] Katano K, Safaei R, Samimi G, Holzer A, Rochdi M, Howell SB. The copper export pump ATP7B modulates the cellular pharmacology of carboplatin in ovarian carcinoma cells. Mol Pharmacol 2003;64:466-473
[33] Ciarimboli G. Membrane transporters as mediators of Cisplatin effects and side effects. Scientifica (Cairo) 2012;2012:473829
[34] Stewart DJ, Benjamin RS, Luna M, Feun L, Caprioli R, Seifert W, Loo TL. Human tissue distribution of platinum after cis-diamminedichloroplatinum. Cancer Chemother Pharmacol 1982;10:51-54
[35] Cavalli F, Tschopp L, Sonntag RW, Zimmermann A. A case of liver toxicity following cis-dichlorodiammineplatinum(II) treatment. Cancer Treat Rep 1978;62:2125-2126
Similar articles:
1.Jia Yin, Joanne Wang.Renal drug transporters and their significance in drug-drug interactions[J]. Acta Pharmaceutica Sinica B, 2016,6(5): 363-373
Similar articles: