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Effect of glutathione depletion on Ifosfamide nephrotoxicity in rats

Sudha Garimella-Krovi1, James E Springate

  • 1Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, USA.

International Journal of Biomedical Science : IJBS
|May 16, 2013
PubMed

Insights

Glutathione depletion worsens ifosfamide kidney injury in rats. Replenishing glutathione may protect against this chemotherapy side effect, suggesting new therapeutic strategies for cancer patients.

Area of Science:

  • Nephrology
  • Oncology
  • Biochemistry

Background:

  • Ifosfamide is a chemotherapy drug that can cause kidney injury.
  • Ifosfamide reduces kidney glutathione levels.
  • Glutathione depletion enhances ifosfamide toxicity in kidney cells.

Purpose of the Study:

  • To investigate the effect of glutathione depletion on ifosfamide-induced kidney injury in vivo.
  • To determine if buthionine sulfoximine exacerbates ifosfamide nephrotoxicity in rats.

Main Methods:

  • Rats were treated with ifosfamide and buthionine sulfoximine.
  • Renal glutathione levels and kidney function markers were assessed.
  • Glucosuria, phosphaturia, and proteinuria were measured.

Main Results:

  • Buthionine sulfoximine significantly reduced renal glutathione content.
  • Ifosfamide caused mild kidney damage (glucosuria, phosphaturia, proteinuria).
  • Concomitant buthionine sulfoximine therapy worsened ifosfamide-induced kidney injury.

Conclusions:

  • Glutathione depletion exacerbates ifosfamide nephrotoxicity in rats.
  • Pharmacological replenishment of glutathione may mitigate ifosfamide-induced renal injury.
  • This suggests potential therapeutic approaches to reduce chemotherapy side effects.
Keywords:
buthionine sulfoximineglutathioneifosfamidekidneytoxic nephropathy

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