Fenofibrate attenuates diabetic nephropathy in experimental diabetic rat's model via suppression of augmented

Nouf Mohamed Al-Rasheed1, Nawal Mohamed Al-Rasheed1,2, Maha Abdelrahman Al-Amin1

  • 1a Pharmacology and Toxicology Department , College of Pharmacy, King Saud University , Riyadh , KSA.

Abstract

Insights

Fenofibrate demonstrates renal protective effects in diabetic nephropathy by reducing key biomarkers and inhibiting the TGF-β1/Smad3 pathway. This suggests fenofibrate as a potential therapeutic strategy for preventing diabetic kidney disease.

Area of Science:

  • Pharmacology
  • Nephrology
  • Molecular Biology

Background:

  • Fibrates, peroxisome proliferator-activated receptor-α ligands, exhibit renal protective effects in diabetic nephropathy (DN).
  • Diabetic nephropathy is a significant complication of diabetes, leading to kidney damage.

Purpose of the Study:

  • To investigate the impact of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in a rat model of STZ-induced DN.
  • To elucidate the molecular mechanisms underlying fenofibrate's renoprotective action in DN.

Main Methods:

  • Diabetes was induced in rats using streptozotocin (STZ).
  • Diabetic rats were treated with fenofibrate (100 mg/kg).
  • Renal biomarkers, including serum creatinine and albumin excretion, and mRNA expression of collagen I, III, TGF-β1, and Smad3 were assessed using RT-PCR after 12 weeks.

Main Results:

  • Fenofibrate significantly reduced serum creatinine and kidney/body weight ratio.
  • Treatment with fenofibrate led to decreased serum albumin excretion.
  • Fenofibrate administration significantly lowered the mRNA expression of collagen I, collagen III, TGF-β1, and Smad3.

Conclusions:

  • Fenofibrate exhibits a protective role in diabetic nephropathy.
  • The renoprotective effects of fenofibrate may be mediated through the inhibition of the TGF-β1/Smad3 signaling pathway.
  • Targeting the TGF-β1/Smad3 pathway represents a potential therapeutic strategy for preventing diabetic nephropathy.