Heme oxygenase 1 and renal ischemia and reperfusion injury: the impact of immunosuppressive drug

Heme oxygenase 1 and renal ischemia and reperfusion injury: the impact of immunosuppressive drug

Author Goncalves, Giselle Martins Google Scholar
Cenedeze, Marcos Antonio Google Scholar
Feitoza, Carla Quarim Google Scholar
Paula, Carolina Batista de Google Scholar
Macusso, Georgia Daniela Google Scholar
Pinheiro, Helady Sanders Google Scholar
Antunes Teixeira, Vicente de Paula Google Scholar
Reis, Marlene Antonia dos Google Scholar
Pacheco-Silva, Alvaro Google Scholar
Camara, Niels Olsen Saraiva Google Scholar
Institution Universidade de São Paulo (USP)
Univ Fed Uberaba
Universidade Federal de São Paulo (UNIFESP)
Abstract Background: Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. in the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Acute cyclosporine nephrotoxicity (ATN) can result from vasoconstriction of the afferent arterioles, which may exacerbate deceased renal transplantation. HO-1 is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in cyclosporine-induced renal dysfunction in an established model of IRLMethods: Cyclosporine (100 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Blood and kidney samples were collected at 24, 48 and 120 h after surgery. Acute tubular necrosis and tubular regeneration were quantified. HO-1 gene transcripts were amplified by real-time PCR.Results: Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05 +/- 0.23 mg/dL), decreasing thereafter. Treatment with cyclosporine caused even more renal dysfunction at 48 h, sustained up to 120 h after reperfusion (1.53 +/- 0.6 mg/dL), when compared to the controls (0.63 +/- 0.09 mg/dL, p < 0,05). Cyclosporine delayed tubular regeneration that was normally higher in controls at day 5 (67.0% vs. 37.6%, p < 0.05). HO-1 was markedly up-regulated after IRI, and its expression was decreased by cyclosporine (2.06 folds). However, prior induction of HO-1 by cobalt protoporphyrin improved renal dysfunction.Conclusions: These results demonstrated that cyclosporine used in ischemic injured organs might also negatively affect post-transplantation recovery. (c) 2006 Elsevier B.V. All rights reserved.
Keywords ischemia and reperfusion injury
cyclosporine
heme oxygenase 1
Language English
Date 2006-12-20
Published in International Immunopharmacology. Amsterdam: Elsevier B.V., v. 6, n. 13-14, p. 1966-1972, 2006.
ISSN 1567-5769 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1966-1972
Origin http://dx.doi.org/10.1016/j.intimp.2006.07.009
Access rights Closed access
Type Article
Web of Science ID WOS:000243216400015
URI http://repositorio.unifesp.br/handle/11600/29316

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