Related Experiment Videos
Cis DDP in combination with selenium and sulfur. Subcellular effect in kidney cells. Electron microprobe study
1SC 27 de l'INSERM, Centre de Microanalyse du CNRS, Faculté de Médecine, Créteil, France.
Abstract:
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.
Insights
Selenium dioxide (SeO2) combined with cisplatin (Cis DDP) effectively protected kidneys from nephrotoxicity. This combination prevented kidney lesions and mineral deposits, unlike sodium thiosulfate (S2O3--).
Area of Science:
- Nephrology
- Oncology
- Toxicology
- Biochemistry
Background:
- Cisplatin (Cis DDP) is a crucial anticancer agent with significant nephrotoxic side effects limiting its clinical application.
- Investigating co-administration of sodium thiosulfate (S2O3--) or selenium dioxide (SeO2) aims to mitigate cisplatin-induced kidney damage.
Purpose of the Study:
- To evaluate the protective effects of SeO2 and/or S2O3-- against Cis DDP-induced nephrotoxicity using ultrastructural and X-ray microanalysis.
- To elucidate the roles of sulfur and selenium in the cellular handling of platinum in kidney lysosomes.
Main Methods:
- Administration of Cis DDP alone, Cis DDP with S2O3--, Cis DDP with SeO2, and Cis DDP with both S2O3-- and SeO2 to assess kidney ultrastructure.
- X-ray microanalysis to detect the presence and distribution of platinum, sulfur, and selenium within kidney lysosomes.
Main Results:
- No kidney lesions were observed with the co-administration of SeO2 and Cis DDP.
- Cis DDP with S2O3-- (or with both S2O3-- and SeO2) showed kidney lesions and intralysosomal platinum and sulfur deposits.
- Co-administration of SeO2 and Cis DDP resulted in no observed mineral deposits in kidney cells.
Conclusions:
- Selenium dioxide (SeO2) demonstrates a protective role against cisplatin (Cis DDP) nephrotoxicity, unlike sodium thiosulfate (S2O3--).
- The findings suggest that selenium may facilitate the urinary elimination of platinum, potentially by associating with it.
- Sulfur's role appears distinct, possibly promoting intralysosomal platinum concentration, whereas selenium may prevent platinum accumulation.