L-Arginine attenuates the ethylene glycol induced urolithiasis in ininephrectomized hypertensive rats: role of KIM-1, NGAL, and NOs

Ren Fail. 2015 May;37(4):709-21. doi: 10.3109/0886022X.2015.1011967. Epub 2015 Feb 16.

Abstract

Background: Ethylene glycol (EG) exposure caused formation of calcium oxalate crystal that led to renal failure, which is associated with higher prevalence of hypertension. L-Arginine is known to have an antioxidant and nephro-protective potential.

Objective: To evaluate the effect of L-arginine against EG-induced urolithiasis in uninephrectomized hypertensive rats.

Material and methods: Uninephrectomized male Wistar rats (180-200 g) were used to induce urinary calculi through oral administration of EG (0.75%) in distilled water. Rats were treated with either distilled water (10 mg/kg, p.o.) or telmisartan (10 mg/kg, p.o.) or Cystone (500 mg/kg, p.o.) or L-arginine (250, 500, and 1000 mg/kg, p.o.) for 28 days. Various hemodynamic, biochemical, molecular, and histological parameters were assessed in kidney and heart.

Results: Rats treated with L-arginine (500 and 1000 mg/kg) significantly restored altered relative organ weight, urine output, urine density, urinary pH, and water intake. EG-induced alterations in electrocardiographic (QRS interval, HR, and ST height) and hemodynamic (SBP, DBP, MABP, and LVEDP) abnormalities were significantly restored by L-arginine (500 and 1000 mg/kg) treatment. It also significantly restored alteration in serum and urine biochemical parameters induced by EG. The elevated oxido-nitrosative stress was also significantly decreased by L-arginine (500 and 1000 mg/kg) treatment. It also significantly down-regulated EG-induced up-regulated renal KIM-1, NGAL, eNOS, and iNOs mRNA expressions. Histological aberrations induced in the renal and cardiac tissues were also ameliorated by l-arginine treatment.

Conclusion: L-Arginine exerts its nephro- and cardio-protective potential in EG-induced urolithiasis in uninephrectomized hypertensive rats via modulation of KIM-1, NGAL, eNOS, and iNOs mRNA expression.

Keywords: Ethylene glycol; KIM-1; NGAL; eNOs; iNOs; l-arginine; uninephrectomy; urolithiasis.

MeSH terms

  • Acute-Phase Proteins / physiology
  • Animals
  • Arginine / therapeutic use*
  • Cell Adhesion Molecules / physiology
  • Ethylene Glycol / administration & dosage
  • Lipocalin-2
  • Lipocalins / physiology
  • Male
  • Nitric Oxide Synthase Type III / physiology
  • Proto-Oncogene Proteins / physiology
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Urolithiasis / chemically induced
  • Urolithiasis / drug therapy*

Substances

  • Acute-Phase Proteins
  • Cell Adhesion Molecules
  • Havcr1protein, rat
  • Lcn2 protein, rat
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Arginine
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Ethylene Glycol