Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase |
| |
Authors: | Katarzyna Winiarska Jolanta M Dzik Mateusz Labudda Dorota Focht Bartosz Sierakowski Aleksandra Owczarek Lukasz Komorowski Wojciech Bielecki |
| |
Institution: | 1. Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, Warsaw, Poland;2. Department of Biochemistry, Faculty of Agriculture and Biology, Warsaw University of Life Sciences – SGGW, Warsaw, Poland;3. Department of Exotic, Laboratory and Non‐domesticated Animals Pathology, Faculty of Veterinary Medicine, Warsaw University of Life Sciences – SGGW, Warsaw, Poland |
| |
Abstract: | Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47phox subunits, elevated level of p47phox phosphorylation, and enlarged phospho‐p47phox and p67phox content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho‐p47phox and p67phox. Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits. |
| |
Keywords: | diabetes melatonin NADPH oxidase nephropathy Zucker diabetic fatty rat |
|
|