Pentavalent antimonial nephrotoxicity in the rat

Area of Science:

• Pharmacology
• Nephrology
• Toxicology

Background:

• Pentavalent antimonials are primary treatments for leishmaniasis.
• Renal function is a critical consideration for drug safety.
• Understanding drug-induced nephrotoxicity is essential for patient care.

Purpose of the Study:

• To investigate the renal effects of Glucantime and Pentostam in a rat model.
• To assess the impact of these antimonials on urine concentrating capacity and renal histology.
• To determine the reversibility and dose-dependency of observed renal changes.

Main Methods:

• Rats were treated with Glucantime or Pentostam at specific doses for 30 days.
• Renal function was assessed by measuring urine osmolality, urinary flow, and free-water clearance.
• Kidney tissues were examined for histopathological alterations.
• Reversibility was studied after a drug-free period.

Main Results:

• Low-dose antimonial treatment (30 mg Sb/100g/day) caused impaired urine concentrating ability, evidenced by decreased urine osmolality, increased urinary flow, and negative free-water clearance.
• These functional changes suggest interference with antidiuretic hormone.
• No significant histopathological changes were seen at low doses, and effects were reversible.
• High-dose Pentostam (200 mg/100g/day) induced acute tubular necrosis.

Conclusions:

• Pentavalent antimonials can induce reversible renal functional disturbances, primarily affecting urine concentration.
• The observed effects are likely due to interference with antidiuretic hormone action.
• High doses of Pentostam pose a risk of acute tubular necrosis, highlighting dose-dependent nephrotoxicity.