title: Probucol inhibited Nox2 expression and attenuated podocyte injury in type 2 diabetic nephropathy of db/db mice.
abstract: The present study was conducted to investigate the effects of probucol on the progression of diabetic nephropathy and the underlying mechanism in type 2 diabetic db/db mice. Eight weeks db/db mice were treated with regular diet or probucol-containing diet (1%) for 12 weeks. Non-diabetic db/m mice were used as controls. We examined body weight, blood glucose, and urinary albumin. At 20 weeks, experimental mice were sacrificed and their blood and kidneys were extracted for the analysis of blood chemistry, kidney histology, oxidative stress marker, and podocyte marker. As a result, 24 h urinary albumin excretions were reduced after probucol treatment. There were improvements of extracellular matrix accumulation and fibronectin and collagen IV deposition in glomeruli in the probucol-treated db/db mice. The reduction of nephrin and the loss of podocytes were effectively prevented by probucol in db/db mice. Furthermore, probucol signiﬁcantly decreased the production of thiobarbituric acid-reactive substances (TBARS), an index of reactive oxygen species (ROS) generation and down-regulated the expression of Nox2. Taken together, our findings support that probucol may have the potential to protect against type 2 diabetic nephropathy via amelioration of podocyte injury and reduction of oxidative stress.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhou
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Detian
authors.initials: D
authors.lastname: Li
mesh_terms: D000419:Albuminuria / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D024141:Collagen Type IV / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D000975:Antioxidants; D024141:Collagen Type IV; D005353:Fibronectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D025721:WT1 Proteins; C113267:nephrin; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D011341:Probucol