Changes of Klotho protein and Klotho mRNA expression in a hydroxy-L-proline induced hyperoxaluric rat model

J Vet Med Sci. 2017 Nov 17;79(11):1861-1869. doi: 10.1292/jvms.17-0340. Epub 2017 Sep 23.

Abstract

Klotho protein is recognized as having a renoprotective effect and is used as a biomarker for kidney injury. We investigated the level of Klotho protein in hyperoxaluria-induced kidney injury and the effects of vitamin E (Vit E) and vitamin C (Vit C) supplementation. Hyperoxaluria was induced by feeding 2% (w/v) Hydroxy-L-proline (HLP) in the drinking water for 21 days. Rats were divided into 5 groups; control (Group 1, n=7), HLP treated rats that received nothing else (Group 2, n=7), Vit E (Group 3, n=6), Vit C (Group 4, n=6) and both Vit E and Vit C (Group 5, n=7). Vit E (200 mg/kg) was injected on days 1, 6, 11 and 16, while Vit C (500 mg/kg) was given intravenously on days 1 and 11. The Klotho protein levels and oxidative status were measured. The expression level of kidney Klotho protein expression was significantly reduced by HLP-treatment, while the mRNA expression was higher (P<0.05), the plasma and kidney malondialdehyde and kidney superoxide dismutase activities were increased, and the kidney reduced glutathione and urinary total antioxidant status were decreased (P<0.05). All of these changes were ameliorated by administration of Vit E, Vit C or especially the co-administration of both. In conclusion, HLP-induced hyperoxaluria reduced the kidney Klotho protein level, which could be restored by Vit E and/or Vit C.

Keywords: Klotho protein; hyperoxaluria; oxidative stress; vitamin C; vitamin E.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / analysis
  • Ascorbic Acid / administration & dosage
  • Glucuronidase / metabolism*
  • Glutathione / analysis
  • Hyperoxaluria / drug therapy*
  • Hyperoxaluria / pathology
  • Kidney / drug effects*
  • Kidney / pathology
  • Klotho Proteins
  • Male
  • Malondialdehyde / analysis
  • Models, Animal
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Superoxide Dismutase
  • Vitamin E / administration & dosage

Substances

  • Antioxidants
  • RNA, Messenger
  • Vitamin E
  • Malondialdehyde
  • Superoxide Dismutase
  • Glucuronidase
  • Klotho Proteins
  • Glutathione
  • Ascorbic Acid