title: Lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.
abstract: BACKGROUND
  Hyperoxaluria is a major risk factor of calcium oxalate stone disease and renal injury is thought to be a significant initiating event. However, the relationship among oxidative stress, renal tubule injury and hyperoxaluria in the progression of nephrolithiasis is unclear, especially in animal models. In the current study, we assess the role of oxidative stress in renal tubular damage in a rat model of chronic hyperoxaluria (HYP) and chronic renal failure induced by hyperoxaluria (HRF) compared to control rats.
  
  
  METHODS
  Urinary excretion of renal tubular enzymes, including lactate dehydrogenase (LDH), alkaline phosphatase (AP), N-acetyl-beta-D-glucosaminidase (NAG), and alpha- and mu-glutathione-S-transferase (alpha-GST and mu-GST, respectively) was quantified in four groups of Sprague-Dawley rats. The study included normal controls, those made hyperoxaluric with ethylene glycol administration (HYP), unilateral nephrectomized controls, and unilateral nephrectomized rats administered ethylene glycol (HRF). Levels of catalase, superoxide dismutase (SOD), glutathione peroxidase (GP), and glutathione transferase (GST) in the renal cortex were measured after 4 weeks and lipid peroxidation was assessed by measuring 8-isoprostane in the urine and lipid hydroperoxide in the renal cortex.
  
  
  RESULTS
  Urinary excretion of NAG, AP, and LDH was elevated after 2 and 4 weeks in the HYP and HRF groups. Urinary levels of mu-GST, a marker of distal tubule damage, were elevated in HRF rats after 4 weeks. alpha-GST levels were similar between control and HYP rats but were lower in HRF rats. Levels of catalase, SOD, GP, and GST in the renal cortex were similar among control, HYP, and unilateral nephrectomized control rats, but were attenuated in the HRF rats after 4 weeks. Renal cortical content of lipid hydroperoxide and urinary 8-isoprostane levels were similar among all groups after 4 weeks.
  
  
  CONCLUSIONS
  Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats is accompanied by enzymuria, which is suggestive of renal tubular damage. The antioxidant capacity of the renal cortex in HYP rats is similar to that of control rats after 4 weeks of treatment; however, this capacity is significantly attenuated in rats that are in renal failure induced by hyperoxaluria, although significant lipid peroxidation is not evident. These results suggest that lipid peroxidation is not the underlying cause of renal injury in hyperoxaluric rats.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610-00275, USA. greenmj@pathology.ufl.edu
authors.forename: Mike L
authors.initials: ML
authors.lastname: Green
authors.forename: Robert W
authors.initials: RW
authors.lastname: Freel
authors.forename: Marguerite
authors.initials: M
authors.lastname: Hatch
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D002129:Calcium Oxalate / Q000652:urine; D006959:Hyperoxaluria / Q000378:metabolism* / Q000473:pathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014545:Urinary Calculi / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species; D002129:Calcium Oxalate