Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.Fundacao de Amparo Pesquisa do Estado de Sao Paulo-FAPESP[07/07139-3]Coordenaco de Aperfeioamento de Pessoal de Nivel Superior-CAPESInstituto Nacional de Ciencia e Tecnologia de Complexos Fluidos (INCT)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNP

Senghor e o Brasil, imagens cruzadas / Senghor et le Brésil, des images croisées

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Grimorio: Translation on the Boundaries of 'Prose'.

This article aims at discussing the translation of the word grimoire, central in Mallarme's conception of language, in a poem called 'Prose' and its four translations into Portuguese. To do so, it will be necessary, in the first place, to have a closer look at this word and its meanings in Mallarme's work and discuss, in a following step, the choices in translation

“Tem alguém aí?”: nota sobre comentários a uma tradução de Jacques Brault

A tradução comentada do texto Il y a quelqu’un? de Jacques Brault levou a uma discussão sobre modos possíveis de apresentação dos comentários produzidos ao longo do processo de tradução. Neste artigo, o intuito é discutir, a partir dos estudos de Ana Cristina Cesar sobre o tema, formas de organização desses comentários

Effects of oestrogen deficiency and 17 beta-estradiol therapy on bone healing in calvarial critical size defects treated with bovine bone graft

Objective: To histomorphometrically analyze the effect of ovariectomy-induced oestrogen deficiency and 17 beta-estradiol therapy on bone healing of surgically created critical-size defects (CSDs) treated with bovine bone graft (BBG).Methods: Forty-eight female rats were randomly assigned to the following 3 experimental groups (n = 16): sham-operated animals (SHAM), ovariectomized animals (OVX) and ovariectomized animals treated with oestrogen (OVX+E2). OVX+E2 animals received daily subcutaneous injections of 17 beta-estradiol (20 mu g/kg) from 8 days after ovariectomy until euthanasia. Thirty days after the surgery, an 8 mm CSD was surgically created in each calvaria of all animals and filled with BBG. Animals were euthanized at either 30 or 60 days postoperative. A histological analysis, percentage of Newly Formed Bone Area (NFBA), osteoblast and osteoclast number was histomorphometrically performed (p <= 0.05).Results: At 30 days, SHAM group (8.82% +/- 2.93) had significantly greater NFBA than OVX (4.66% +/- 1.35) and OVX+E2 groups (5.85% +/- 4.08) (p <= 0.05). At 60 days, SHAM group (11.51% +/- 3.08) and OVX+E2 group (9.84% +/- 1.87) had significantly greater NFBA than OVX animals (5.12% +/- 0.68) (p <= 0.05). Fewer osteoblasts were observed in the OVX group at 30 (763.40 +/- 121.60) and 60 (696.60 +/- 80.92) days than in the SHAM group at 30 days (1356.00 +/- 95.38). Fewer osteoclasts were observed in the OVX+E2 group (3.25 +/- 2.16) than in the SHAM (9.75 +/- 1.82) and OVX (12.75 +/- 1.47) groups at 30 days (p <= 0.05).Conclusions: Oestrogen deficiency compromises bone healing in calvarial CSDs treated with BBG in ovariectomized rats. After 60 days post-surgery, 17 beta-estradiol therapy improved bone healing in calvarial CSDs treated with BBG in ovariectomized rats.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP