Cis DDP in combination with selenium and sulfur. Subcellular effect in kidney cells. Electron microprobe study

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.