Amelioration of lithiatic injury to renal tissue by candesartan and sodium thiosulfate in a rat model of nephrolithiasis

PLoS One. 2021 May 13;16(5):e0251408. doi: 10.1371/journal.pone.0251408. eCollection 2021.

Abstract

Aim: Nephrolithiasis is a chronic metabolic condition affecting 10% of population worldwide. The present study aimed to investigate the possible protective role of candesartan (CAND) and sodium thiosulfate (STS) in ameliorating ethylene glycol (EG) induced nephrolithiasis.

Methods: One hundred male Wistar rats were divided into five groups: Normal control group, nephrolithiasis (EG) group (1% EG in drinking water), Cystone (CYS) group (EG + 750 mg/kg CYS, orally, once daily), STS group (EG + 0.4 gm/kg STS, intraperitoneally, 3 times/week) and CAND group (EG + 70 μg/mL CAND in drinking water). Treatments and EG administration commenced on the same day and continued for 28 days. CYS was used as reference drug. Urine, blood, and renal tissues were collected at the end of the experiment for assessment of kidney function tests (serum creatinine and urea), urinary (8-hydroxydeoxyguanosine (8-OHdG), calcium and oxalate), inflammatory and oxdative stress biomarkers (transforming growth factor beta (TGF-β), osteopontin (OPN) and ratio of reduced glutathione to oxidized glutathione (GSH/GSSG)) in renal tissue.

Results: Serum (creatinine and urea), urinary (8-OHdG and oxalate) and renal (OPN and TGF-β) were significantly reduced in CAND and STS groups compared to EG group. Furthermore, renal GSH/GSSG and urinary calcium were significantly increased in CAND and STS groups compared to EG group. Histopathological results support the biochemical findings; CAND and STS groups showed less retention of crystals and necrotic damage in kidney. Also, microscopic examination of urine revealed less crystal for CAND and STS groups.

Conclusion: Candesartan and sodium thiosulfate exhibited protective effect against nephrolithiasis.

MeSH terms

  • Animals
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds / therapeutic use*
  • Ethylene Glycol
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Nephrolithiasis / chemically induced
  • Nephrolithiasis / drug therapy*
  • Nephrolithiasis / pathology
  • Protective Agents / therapeutic use*
  • Rats
  • Rats, Wistar
  • Tetrazoles / therapeutic use*
  • Thiosulfates / therapeutic use*

Substances

  • Benzimidazoles
  • Biphenyl Compounds
  • Protective Agents
  • Tetrazoles
  • Thiosulfates
  • Ethylene Glycol
  • sodium thiosulfate
  • candesartan

Grants and funding

The author(s) received no specific funding for this work.