Prevention by tretinoin (all-trans-retinoic acid) of age-related renal changes

The present work shows that dietary tretinoin (all-trans-retinoic acid) supplementation may be a useful manoeuvre for the prevention of age-related renal changes. 18-month-old male Fischer 344 rats fed during three months with standard chow plus tretinoin (1 mg/kg/day) did not exhibit any adverse effect in terms of bodyweight, urinary volume, renal handling of sodium and both hematological and blood chemistry parameters. Although the diet did not reduce age-related proteinuria nor renal lipid peroxidation, glomerular filtration rate and renal cortex protein content were, respectively, 30% higher and 30% lower than in age-matched control rats. These results suggest that dietary tretinoin supplementation may be a useful manoeuvre to slow the progression of age-related renal changes. Since glomerular H2O2 production increases during renal aging in rats, we studied the effect of tretinoin on the biology of cultured glomerular rat mesangial cells exposed to H2O2. Preincubation with tretinoin abolished cell proliferation or cell death induced, respectively, by low and high concentrations of H2O2. These results suggest that the modulation of the cellular actions of H2O2 may be relevant in the mechanisms through which tretinoin prevents age-related renal changes.