Subcellular localization of cis-dichlorodiammineplatinum(II) in rat kidney and liver

Choie, David D.; Campo, A A del; Guarino, Anthony M.

doi:10.1016/0041-008x(80)90086-1

Cited by 69 publications

(22 citation statements)

References 15 publications

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“…Renal high Pt content, which was accumulated 6 hr after i.p. injection of cisplatin, decreased thereafter at a relatively rapid rate, but the rate of decrease in the Pt content in the kidney was relatively slow from 48 hr over several days in rats and mice (16)(17)(18). Then, we examined whether the antioxidant, given 24 hr before the injection of cisplatin, could have the effect on Pt distribution 3 days after cisplatin injection.…”

Section: Resultsmentioning

confidence: 99%

Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues.

et al. 1987

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Abstract-Cisplatin(cis-diamminedichloroplatinum II), an anticancer chemo therapeutic agent with the dose-limiting side effect of nephrotoxicity, caused a statistically significant increase in lipid peroxidation, monitored by measuring the production of malondialdehyde, in rat kidney 72 hr after injection. Treatment of rats beforehandwith the antioxidant a-tocopherol or N-N'-diphenyl-p-phenyl enediamine (DPPD) effectively decreased such peroxidation. DPPD was a more effective inhibitor than a-tocopherol, since it is known for its ability to scavenge free radicals more powerfully.The ability of renal cortical slices to accumulate p-aminohippurate (PAH) was examined as a biochemical parameter that would change in nephrotoxicity.The ability to accumulate PAH by the incubated slices decreased 72 hr after administration of cisplatin. The pretreatment with DPPD prevented the decrease in PAH accumulation in the slices from rats treated with cisplatin.

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Section: Resultsmentioning

confidence: 99%

Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues.

et al. 1987

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“…DEM affected GSH in the slices without affecting the mitochondrial GSH level, suggesting that DEM depleted the cytoplasmic GSH. The kidney accumulates high concentrations of cisplatin injected into rats (14), and the drug shows subcellular localization in kidney (15). In our study, cisplatin moved into the mitochondria in rat kidney cortical slices in vitro, and such movement was not affected by the decrease in cytoplasmic GSH caused by DEM.…”

mentioning

confidence: 61%

Cisplatin-induced injury to calcium uptake by mitochondria in glutathione-depleted slices of rat kidney cortex.

Kameyama

Gemba

1991

Jpn.J.Pharmacol

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“…14,15) The selective accumulation and retention of CDDP in the kidney is regarded as the most critical aspect of its nephrotoxicity. Therefore, we examined the stability of the complex against the tissue protein binding by use of a kidney homogenate, which is a simple method for the study of drug binding.…”

Section: Discussionmentioning

confidence: 99%

Stability of a Cisplatin-Chondroitin Sulfate A Complex in Plasma and Kidney in Terms of Protein Binding.

Zhang

Suenaga

et al. 2001

Biological & Pharmaceutical Bulletin

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In spite of the successful application of cisplatin (CDDP) as a chemotherapy agent, alone or in combination against several solid tumors, 1,2) it would be desirable to modify it by synthetic chemical or pharmaceutical formulation methods, in order to overcome some of its side effects, especially its nephrotoxicity.3) In order to reduce the nephrotoxicity, which is associated with CDDP treatment, we developed a CDDP complex using chondroitin sulfate A (CSA), a polycarboxyl polysaccharide. The CDDP-CSA complex had the same activity as the parent drug but showed reduced nephrotoxicity at high doses of CDDP. 4) Thus, the results suggest that CDDP-CSA might reversibly release the active parent drug, due to reversible binding with the carboxyl group of the CSA, as observed with other carbohydrate compounds. 5)Therefore, it is important to examine the stability of the CDDP-CSA complex in the circulation, since plasma proteins may potentially compete for CDDP to form irreversibly bound species. Approximately 90% of the platinum in the blood exists in a protein-bound form following intravenous administration of CDDP. 6,7)Based on the above objective, we compared the plasma levels of total and protein-free platinum for both CDDP and the CDDP-CSA complex following intravenous administration. The availability of protein-free platinum in the circulation was used to evaluate the stability toward the protein binding. Moreover, the stability of the complex in the kidney was examined by incubation with a kidney homogenate. MATERIALS AND METHODSChemicals and Animals CDDP was purchased from Sigma Chemical Company (St. Louis, MO, U.S.A.). Chondroitin sulfate A (CSA) with a mean molecular weight of 23 KDa was obtained from Seikagaku Corporation (Kanagawa, Japan). A CDDP-CSA complex was prepared by dissolving CDDP (1 mg/ml) and CSA (8.4 mg/ml) in deionized water, followed by shaking for 2 d until a reaction equilibrium of 80-85% of the CDDP forming a complex with the CSA had been reached. All other chemicals were of analytical grade. 7-week-old male Wistar rats (230-250 g) were used in the experiments.Measurement of Total and Unbound Platinum Plasma Disposition Cannulations were performed on rats via the femoral vein and artery using polyethylene tubing (PE50) as described previously.4) CDDP was dissolved in saline at a concentration of 1 mg/ml; the prepared complex (containing 1 mg/ml of CDDP) was made iso-osmotic by the addition of glucose. The freshly prepared solution, CDDP or CDDP-CSA was then administered at a dose of 2 mg/kg via the formal vein. Blood samples (0.3-0.4 ml) were collected from the femoral artery at 2, 5, 10, 30, 60, 90, 120, and 180 min into heparinized microtubes, followed by rapid centrifugation, in order to isolate the plasma immediately. Following this procedure, 0.2 ml of plasma was added to an equal volume of a cold mixture of 10% TCA and 5% HCl, and the supernatant was analyzed for TCA-soluble platinum which represents the sum of the free and reversibly bound species. 8)The remaining plasma samples were u...

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Subcellular localization of cis-dichlorodiammineplatinum(II) in rat kidney and liver

Cited by 69 publications

References 15 publications

Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues.

Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues.

Cisplatin-induced injury to calcium uptake by mitochondria in glutathione-depleted slices of rat kidney cortex.

Stability of a Cisplatin-Chondroitin Sulfate A Complex in Plasma and Kidney in Terms of Protein Binding.

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