Cis DDP in combination with selenium and sulfur. Subcellular effect in kidney cells. Electron microprobe study.
Cis DDP is an anticancer agent used in the treatment of diverse cancers, but its use has been limited by its nephrotoxic effect. We sought to modify this major toxic side effect by the addition of S2O3-- (sodium thiosulfate) or SeO2 (selenium dioxide) or both. In the present study, only ultrastructural and X-ray microanalysis data are reported. No kidney lesions were observed after the administration of SeO2 and Cis DDP in contrast to Cis DDP with S2O3-- or with S2O3-- plus selenium. An organelle of the kidney cell, the lysosome, has a particular role in the concentration of mineral elements in this cell. Platinum was observed in the lysosome along with sulfur, after the administration of Cis DDP and S2O3. Platinum, selenium and sulfur were observed after administration of SeO2, S2O3 and Cis DDP. No mineral deposits were observed after administration of SeO2 and Cis DDP. The role of sulfur seems to be very different from that of selenium. We hypothesize that sulfur favors the intralysosomal concentration of platinum or that selenium associates with platinum. The fact that selenium is not reabsorbed by the kidney cell seems to favor the hypothesis of urinary elimination of platinum. The present work confirms our previous study concerning the role of SeO2 in combination with Cis DDP.
Berry
J P
JP
SC 27 de l'INSERM, Centre de Microanalyse du CNRS, Faculté de Médecine, Créteil, France.
Lespinats
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G
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D004577:Electron Probe Microanalysis; D007668:Kidney / Q000032:analysis / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008247:Lysosomes / Q000032:analysis / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008903:Minerals / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*; D013455:Sulfur / Q000494:pharmacology*
D008903:Minerals; D013455:Sulfur; D012643:Selenium; D002945:Cisplatin