Beneficial effect of retinoic acid on the outcome of experimental acute renal failure

Nephrol Dial Transplant. 2004 Oct;19(10):2464-71. doi: 10.1093/ndt/gfh400. Epub 2004 Aug 17.

Abstract

Background: Retinoic acid (RA) exerts beneficial effects on vascular remodelling and experimental nephritis, and plays a role in kidney development. Pathological changes caused by acute renal failure (ARF) result in high mortality. We determined whether RA ameliorates ARF-induced pathology caused by potassium dichromate (PD).

Methods: Adult Wistar female rats (210-250 g) were randomly allocated to four groups: (i) an ARF group that received PD [15 mg/kg body weight (bw), single dose subcutaneously]; (ii) a group that received PD plus RA (1 mg/kg bw) beginning at 5 days before PD and that continued for 14 additional days; (iii) a group that received PD plus thyroxine (T(4); 8 micro g/100 g bw) with RA; and (iv) a group that received only the vehicle for PD (saline solution). We evaluated functional, biochemical and morphological characteristics of the kidneys.

Results: PD-induced alterations in serum creatinine, creatinine clearance (C(cr)) and fractional excretion of sodium (FeNa) were less severe when rats received RA. PD increased lipoperoxidation and this alteration was partially blocked by RA. Animals undergoing ARF showed severe histological injury (brush border loss, acidophilia, oedema, pyknosis, karyorhexis, cell detachment and disruption of the basement membrane). These alterations were less severe in RA-treated rats, indicating a protective effect on functional and morphological alterations. Alterations in urinary sediment were reduced by RA. The simultaneous administration of T(4) with RA did not produce additional protection.

Conclusion: RA exerted beneficial effects on the duration and severity of renal damage induced by PD in a model of renal failure resembling ARF in humans. The protective effect of RA may be mediated by diminished lipoperoxidative damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / pathology*
  • Acute Kidney Injury / physiopathology*
  • Acute Kidney Injury / urine
  • Animals
  • Creatinine / metabolism
  • Diuresis / drug effects
  • Drug Combinations
  • Drug Synergism
  • Female
  • Lipid Peroxidation / drug effects
  • Natriuresis / drug effects
  • Potassium Dichromate
  • Rats
  • Rats, Wistar
  • Severity of Illness Index
  • Thyroxine / pharmacology
  • Tretinoin / pharmacology*
  • Weight Loss / drug effects

Substances

  • Drug Combinations
  • Tretinoin
  • Creatinine
  • Thyroxine
  • Potassium Dichromate