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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 (<jats:styled-content style=\"fixed-case\">ZDF<\/jats:styled-content>) rats; (ii) untreated obese diabetic (fa\/fa) <jats:styled-content style=\"fixed-case\">ZDF<\/jats:styled-content> rats; and (iii) <jats:styled-content style=\"fixed-case\">ZDF<\/jats:styled-content> 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, <jats:styled-content style=\"fixed-case\">ZDF<\/jats:styled-content> fa\/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47<jats:sup>phox<\/jats:sup> subunits, elevated level of p47<jats:sup>phox<\/jats:sup> phosphorylation, and enlarged phospho\u2010p47<jats:sup>phox<\/jats:sup> and p67<jats:sup>phox<\/jats:sup> content in membrane. Melatonin administration to <jats:styled-content style=\"fixed-case\">ZDF<\/jats:styled-content> 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\u2010p47<jats:sup>phox<\/jats:sup> and p67<jats:sup>phox<\/jats:sup>. 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.<\/jats:p>","DOI":"10.1111\/jpi.12296","type":"journal-article","created":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T04:52:59Z","timestamp":1446180779000},"page":"109-117","source":"Crossref","is-referenced-by-count":43,"title":["Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on <scp>NADPH<\/scp> oxidase"],"prefix":"10.1111","volume":"60","author":[{"given":"Katarzyna","family":"Winiarska","sequence":"first","affiliation":[{"name":"Department of Metabolic Regulation Institute of Biochemistry Faculty of Biology University of Warsaw Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta 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