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Retinoic acid improves recovery after nephrectomy and decreases renal TGF‐β1 expression. Gender‐related effects
Authors:Dealmy Delgadillo  Olivier Barbier  Gerardo Sierra  Jose L Reyes
Institution:1. Pharmacology Department, Center for Research and Advanced Studies, National Polytechnic Institute of Mexico (Cinvestav‐IPN), , C.P. 07360 Mexico City, Mexico;2. Toxicology Department, Center for Research and Advanced Studies, National Polytechnic Institute of Mexico (Cinvestav‐IPN), , C.P. 07360 Mexico City, Mexico;3. Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies, National Polytechnic Institute of Mexico (Cinvestav‐IPN), , C.P. 07360 Mexico City, Mexico
Abstract:End‐stage renal disease is a cause for death worldwide. Renal transplant is a therapeutic alternative, restricted by the scant number of donors. Function of the donor kidney is under risk of adverse circumstances such as fibrosis, where profibrotic effect of transforming growth factor beta 1 (TGF‐β1) plays a key role. Efforts to diminish risks of damage in the remnant kidney of the donor are required. Vitamin A represents one alternative. It has beneficial effects on some nephropathies, mainly those related to oxidative stress. It also participates in normal intrauterine renal development. We studied the effect of all‐trans retinoic acid (ATRA), active form of vitamin A, on postnephrectomy compensatory growth, in male or female rats. Compensatory growth and renal function were evaluated on four experimental groups: Control without treatment (CTL), ATRA‐treated intact rats (CTL + RA), nephrectomized rats (NFX), and ATRA‐treated nephrectomized rats (NFX + RA). We evaluated glomerular function (inulin clearance), tubular function (fractional excretions of sodium and potassium), and urinary flow. Renal mass was also estimated. In ATRA‐treated animals, compensatory growth was higher than in nephrectomized rats without treatment. Hyperfiltration after nephrectomy was less intense in ATRA‐treated female than in male rats. In tubular functions, effect of ATRA was more evident in female than in male rats. Glomerular expression of TGF‐β1 was lower in ATRA‐treated animals than in controls. ATRA reduced intensity and duration of compensatory changes after nephrectomy, improving recovery.
Keywords:renal compensatory growth  retinoic acid  TGF‐β  1
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