Navegando por Palavras-chave "Heme oxygenase 1"
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- ItemAcesso aberto (Open Access)Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats(Biomed Central Ltd, 2013-01-16) Ptilovanciv, Ellen O. N. [UNIFESP]; Fernandes, Gabryelle S. [UNIFESP]; Teixeira, Luciana C. [UNIFESP]; Reis, Luciana A. [UNIFESP]; Pessoa, Edson A. [UNIFESP]; Convento, Marcia B. [UNIFESP]; Simoes, Manuel J. [UNIFESP]; Albertoni, Guilherme A. [UNIFESP]; Schor, Nestor [UNIFESP]; Borges, Fernanda T. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1) is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. the goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. the hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME). A group of normoglycemic, untreated rats was used as the control (CTL).Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS) were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. in the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group.There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. in the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. in conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant activity of HO-1.
- ItemSomente MetadadadosModulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury(Birkhauser Verlag Ag, 2010-03-01) Feitoza, Carla Q. [UNIFESP]; Semedo, Patricia [UNIFESP]; Goncalves, Giselle M. [UNIFESP]; Cenedeze, Marcos A. [UNIFESP]; Pinheiro, Helady S.; Pavao dos Santos, Oscar Fernando [UNIFESP]; Landgraf, Richardt Gama [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Saraiva Camara, Niels Olsen [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Univ Fed Juiz de Fora; Hosp Israelita Albert EinsteinThis work explored the role of inhibition of cyclooxygenases (COXs) in modulating the inflammatory response triggered by acute kidney injury.C57Bl/6 mice were used.Animals were treated or not with indomethacin (IMT) prior to injury (days -1 and 0).Animals were subjected to 45 min of renal pedicle occlusion and sacrificed at 24 h after reperfusion. Serum creatinine and blood urea nitrogen, reactive oxygen species (ROS), kidney myeloperoxidase (MPO) activity, and prostaglandin E2 (PGE(2)) levels were analyzed. Tumor necrosis factor (TNF)-alpha, t-bet, interleukin (IL)-10, IL-1 beta, heme oxygenase (HO)-1, and prostaglandin E synthase (PGES) messenger RNA (mRNA) were studied. Cytokines were quantified in serum.IMT-treated animals presented better renal function with less acute tubular necrosis and reduced ROS and MPO production. Moreover, the treatment was associated with lower expression of TNF-alpha, PGE(2), PGES, and t-bet and upregulation of HO-1 and IL-10. This profile was mirrored in serum, where inhibition of COXs significantly decreased interferon (IFN)-gamma, TNF-alpha, and IL-12 p70 and upregulated IL-10.COXs seem to play an important role in renal ischemia and reperfusion injury, involving the secretion of pro-inflammatory cytokines, activation of neutrophils, and ROS production. Inhibition of COX pathway is intrinsically involved with cytoprotection.