Protective effect of proanthocyanidins against doxorubicin-induced nephrotoxicity in rats

El-Sayed M El-Sayed1, Ahmed M Mansour1, Waleed S El-Sawy2

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

Insights

Proanthocyanidins (PAs) protect against Doxorubicin (DOX)-induced kidney damage by reducing oxidative stress and inflammation. This study demonstrates PAs

Area of Science:

  • Pharmacology
  • Toxicology
  • Nephrology

Background:

  • Doxorubicin (DOX) is a widely used chemotherapy agent with significant nephrotoxic side effects.
  • Kidney damage from DOX can manifest as impaired function and structural damage.
  • Identifying protective agents against DOX-induced nephrotoxicity is crucial for improving cancer patient outcomes.

Purpose of the Study:

  • To evaluate the protective effects of proanthocyanidins (PAs) against Doxorubicin (DOX)-induced nephrotoxicity in a rat model.
  • To investigate the underlying mechanisms of PA-mediated protection, focusing on oxidative stress and inflammation.

Main Methods:

  • Rats were pretreated with proanthocyanidins (PAs) orally before and after a single intravenous dose of Doxorubicin (DOX).
  • Kidney function was assessed by measuring serum urea and creatinine levels.
  • Oxidative stress markers, including malondialdehyde, nitric oxide, reduced glutathione (GSH), and superoxide dismutase activity, were analyzed.
  • Inflammatory markers (tumor necrosis factor alpha, cyclooxygenase-2) and apoptotic activity (caspase-3) were quantified.
  • Histopathological examination of kidney tissues was performed.

Main Results:

  • DOX administration significantly increased kidney weight, serum urea and creatinine, and kidney levels of oxidative stress and inflammatory markers.
  • DOX treatment led to decreased final body weight, serum albumin, and kidney antioxidant enzyme activities.
  • PA pretreatment significantly ameliorated DOX-induced changes in kidney function and oxidative stress parameters.
  • Histopathology confirmed that PAs protected kidney tissues from DOX-induced damage.

Conclusions:

  • Proanthocyanidins (PAs) exhibit significant nephroprotective effects against Doxorubicin (DOX)-induced kidney injury in rats.
  • The protective mechanisms of PAs involve antioxidant, anti-inflammatory, and anti-apoptotic activities.
  • PAs represent a potential therapeutic strategy to mitigate the renal toxicity associated with DOX chemotherapy.

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