title: Targeting heme oxygenase-1 in early diabetic nephropathy in streptozotocin-induced diabetic rats.
abstract: Diabetic nephropathy (DN) is one of the most common microvascular diabetic complications. This study was designed to evaluate the possible protective effect and underlying mechanisms of HO-1 induction in streptozotocin (STZ)-induced early DN in rats. The diabetic rats were divided into three groups: STZ-diabetic, cobalt protoporphyrin (CoPP)-treated diabetic, and zinc protoporphyrin IX (ZnPP)-treated diabetic groups. Compared to the STZ-diabetic group, CoPP-induced HO-1 upregulation improved the diabetic state and renal functional parameters, suppressed the renal proinflammatory marker, NF-κB, abrogated the elevated renal hydroxyprolin, and decreased the enhanced renal nicotinamide adenine dinucleotide phosphate oxidase activity with parallel reduction of urinary oxidative stress markers. On the contrary, treatment with ZnPP abrogated HO-1 levels, aggravated the diabetic condition with further increases in renal oxidative stress, fibrotic and inflammatory markers, and exacerbated renal dysfunction in diabetic animals. These findings suggest that the reduced diabetic renal injury upon HO-1 induction implicates the role of HO-1 induction as a potential treatment for DN.
authors.affiliation: 1 Physiology Department, Faculty of Medicine, Tanta University , Tanta, Egypt.
authors.forename: R
authors.initials: R
authors.lastname: Abo El Gheit
authors.affiliation: 1 Physiology Department, Faculty of Medicine, Tanta University , Tanta, Egypt.
authors.forename: M N
authors.initials: MN
authors.lastname: Emam
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006909:Hydroxyproline / Q000378:metabolism; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D058990:Molecular Targeted Therapy; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; C000609942:ICAM1 protein, rat; D007328:Insulin; D016328:NF-kappa B; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C017803:zinc protoporphyrin; D013311:Streptozocin; C007095:cobaltiprotoporphyrin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D019255:NADPH Oxidases; D006909:Hydroxyproline
keywords: cobalt protoporphyrin; diabetic nephropathy; heme oxygenase; renal hydroxyprolin; zinc protoporphyrin IX