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PREVENTION OF CISPLATIN-INDUCED NEPHROTOXICITY BY METHIMAZOLE

Osman1, El-Sayed, El-Demerdash

  • 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt,

Pharmacological Research
|March 14, 2000
PubMed

Insights

Methimazole protects against cisplatin-induced kidney damage by reducing serum creatinine and blood urea nitrogen. This antithyroid drug preserves kidney function without compromising cisplatin's cancer-fighting efficacy in mice.

Area of Science:

  • Nephrology
  • Pharmacology
  • Oncology

Background:

  • Cisplatin is a vital chemotherapy drug for solid tumors.
  • Nephrotoxicity is a significant side effect limiting cisplatin dosage.
  • Methimazole, an antithyroid drug, shows potential for chemical nephrotoxicity protection.

Purpose of the Study:

  • To investigate cisplatin's nephrotoxic effects at the nuclear level in rat kidneys.
  • To evaluate methimazole's protective potential against cisplatin-induced nephrotoxicity.
  • To examine the combined effect of methimazole and cisplatin on cancer cells.

Main Methods:

  • Rats were administered a therapeutic dose of cisplatin (7 mg/kg).
  • Methimazole (40 mg/kg) was given 30 minutes before cisplatin.
  • Biochemical markers (creatinine, BUN, lipid peroxides, glutathione) and DNA fragmentation were analyzed.
  • Kidney histopathology was performed.
  • Ehrlich ascites carcinoma (EAC)-bearing mice were used to assess combined drug efficacy.

Main Results:

  • Cisplatin significantly increased serum creatinine, BUN, and kidney lipid peroxides.
  • Cisplatin induced kidney DNA fragmentation and histopathological damage.
  • Methimazole pretreatment significantly reduced cisplatin's nephrotoxic biochemical and histological effects.
  • Combined treatment in EAC-bearing mice maintained cisplatin's cytotoxic activity.

Conclusions:

  • Methimazole demonstrates significant nephroprotective effects against cisplatin-induced kidney damage.
  • Methimazole does not interfere with the oncolytic action of cisplatin.
  • The combination of methimazole and cisplatin is a promising therapeutic strategy warranting further investigation.

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