Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices

Kanou, Takehiro; Uozumi, Jiro; Soejima, Kyoko; Tokuda, Yuji; Masaki, Zenjiro

doi:10.1007/s10157-004-0304-0

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…8A). The nephrotoxic pattern of oxaliplatin observed in the renal slice with collapsed and nonperfused lumens resembled to that of cisplatin (Kanou et al, 2004). It is likely that oxaliplatin would be accumulated in the renal slice without efflux systems, thereby exacerbating its toxicity.…”

Section: Discussionmentioning

confidence: 86%

Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1–3 and Multidrug and Toxin Extrusion Family)

Yonezawa

Masuda²,

Yokoo

et al. 2006

The Journal of Pharmacology and Experimental Therapeutics

302

238

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We have examined the role of the human organic cation transporters [hOCTs and human novel organic cation transporter (hOCTN); SLC22A1-5] and apical multidrug and toxin extrusion (hMATE) in the cellular accumulation and cytotoxicity of platinum agents using the human embryonic kidney (HEK) 293 cells transiently transfected with the transporter cDNAs. Both the cytotoxicity and accumulation of cisplatin were enhanced by the expression of hOCT2 and weakly by hOCT1, and those of oxaliplatin were also enhanced by the expression of hOCT2 and weakly by hOCT3. The hOCT-mediated uptake of tetraethylammonium (TEA) was markedly decreased in the presence of cisplatin in a concentration-dependent manner. However, oxaliplatin showed almost no influence on the TEA uptakes in the HEK293 cells expressing hOCT1, hOCT2, and hOCT3. The hMATE1 and hMATE2-K, but not hOCTN1 and OCTN2, mediated the cellular accumulation of cisplatin and oxaliplatin without a marked release of lactate dehydrogenase. Oxaliplatin, but not cisplatin, markedly decreased the hMATE2-K-mediated TEA uptake. However, the inhibitory effect of cisplatin and oxaliplatin against the hMATE1-mediated TEA uptake was similar. The release of lactate dehydrogenase and the cellular accumulation of carboplatin and nedaplatin were not found in the HEK293 cells transiently expressing these seven organic cation transporters. These results indicate that cisplatin is a relatively good substrate of hOCT1, hOCT2, and hMATE1, and oxaliplatin is of hOCT2, hOCT3, hMATE1, and hMATE2-K. These transporters could play predominant roles in the tissue distribution and anticancer effects and/or adverse effects of platinum agent-based chemotherapy.Four platinum-based anticancer drugs are currently registered for clinical use. cis-Diamminedichloroplatinum II (cisplatin) has been clinically used for over 30 years and continues to play an essential role in cancer chemotherapy against solid tumors of the prostate, bladder, colon, lung, testis, liver, and brain (Ho et al., 2003). However, severe nephrotoxicity limits its clinical application because it was reported that an increase in the serum creatinine concentration was observed in 41% of patients treated with a high dose of cisplatin (de Jongh et al., 2003). cis-Diammine(1,1-cyclobutanedicarboxylato)platinum II (carboplatin), trans-L-1,2-diaminocyclohexaneoxalatoplatinum II (oxaliplatin), and cis-diammineglycolatoplatinum (nedaplatin) are analogs of cisplatin and show a lowered nephrotoxicity compared with cisplatin. However, it is not clear why the nephrotoxicity of these analogs is low, although cisplatin induces severe nephrotoxicity. The chemical structures of platinum agents are shown in Fig.

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Section: Discussionmentioning

confidence: 86%

Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1–3 and Multidrug and Toxin Extrusion Family)

Yonezawa

Masuda²,

Yokoo

et al. 2006

The Journal of Pharmacology and Experimental Therapeutics

302

238

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“…Unlike other platinum compounds, carboplatin is excreted mainly via glomerular filtration (Sorensen et al, 1992) and is not transported by organic cation transporters including hOCT1 and hOCT2 (Yonezawa et al, 2006). Moreover, a previous study reported that the accumulation of p-aminohippurate (a typical substrate of hOATs) was not inhibited by carboplatin in the experiment using rat renal cortical slices (Kanou et al, 2004). Thus, it is unlikely that lansoprazole inhibits tubular secretion of carboplatin.…”

Section: Discussionmentioning

confidence: 96%

Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3

Ikemura

Hamada

Kaya

et al. 2016

Drug Metabolism and Disposition

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Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (K m = 68.3 6 11.1 mM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC 50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 6 0.17 mM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interactioninduced side effects for achievement of safe and appropriate chemotherapy with pemetrexed.

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“…3 The platinum drug-induced glutathione (GSH) depletion is a determinant step that leads to oxidative stress and to acute renal failure. Kanou et al have shown that the two platinum drugs (cisplatin and oxaliplatin) have similar in vitro nephrotoxicity, 6 whereas in vivo, only cisplatin is nephrotoxic as reported by Ali. 4 This work has been conducted to verify the comparative actions of both platinum compounds on biomarkers of oxidative stress in human embryonic kidney (HEK) 293 cells and further to investigate if the established antioxidant compound curcumin would affect these biomarkers.…”

Section: Introductionmentioning

confidence: 72%

“…4 The reason why oxaliplatin is less nephrotoxic in vivo than cisplatin is not clear, considering that in rat renal cortical slices (in vitro) the nephrotoxicity pattern of both oxaliplatin and cisplatin is similar. 6 Curcumin (diferuloyl methane) is the active principal curcuminoid in the traditional herbal remedy and the Indian curry spice turmeric (Curcuma longa). 7 It is undergoing clinical trials for different types of cancer, Alzheimer's disease, and ulcerative colitis.…”

Section: Introductionmentioning

confidence: 99%

Effect of Curcumin on Cisplatin- and Oxaliplatin-Induced Oxidative Stress in Human Embryonic Kidney (HEK) 293 Cells

2011

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Generation of reactive oxygen species (ROS) is involved in the nephrotoxicity of platinum anticancer drugs. This study involved incubation of human embryonic kidney (HEK) 293 cells in cell culture media supplemented with cisplatin or oxaliplatin in the presence or absence of curcumin, a well-studied antioxidant. Thereafter several indices of oxidative stress have been measured, which included glutathione (GSH), total antioxidant capacity (TAC), and antioxidant enzymes [(superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX)]. The impact of platinum drugs on cells viability, lipid peroxidation, and lactate dehydrogenase leakage was also examined. The results show that at both acute (60 min) and chronic (24 h) durations of incubation, cisplatin and oxaliplatin induced oxidative stress as evidenced by significant inhibition of the activities of SOD, CAT, and GPX enzymes as well as significant reduction of the concentrations of GSH and TAC. Curcumin ameliorated the oxidative stress induced by these insults by significantly restoring the measured oxidative indices. Our findings provide evidence that curcumin significantly ameliorates oxidative stress induced by both cisplatin and oxaliplatin in HEK cells.

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Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices

Cited by 4 publications

References 17 publications

Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1–3 and Multidrug and Toxin Extrusion Family)

Cisplatin and Oxaliplatin, but Not Carboplatin and Nedaplatin, Are Substrates for Human Organic Cation Transporters (SLC22A1–3 and Multidrug and Toxin Extrusion Family)

Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3

Effect of Curcumin on Cisplatin- and Oxaliplatin-Induced Oxidative Stress in Human Embryonic Kidney (HEK) 293 Cells

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