Cytoprotective role of heme oxygenase-1 upregulation in progressive renal disease

Objective: This study evaluated the ability of heme oxygenase-1 to prevent or reverse renal fibrosis. Methods: Sprague-dawley male rats were submitted to unilateral ureteral obstruction and divided into groups: non-treated and hemin. Biochemical and histological analyses were performed. We also conducted RT-PCR to verify the expression of heme oxygenase-1, MCP-1, IL1-beta, IL-6, TNF-alfa, COL-I, COL-III, PAI-1 and fibronectin mRNA. Results: heme oxygenase-1 expression significantly increased in treated animals. The non treated group showed significantly higher levels of proteinuria than the Hemin group. The protein/urinary creatinine ratio in obstructed pelvis was also higher in non treated group, which also showed greater albuminuria and higher percentage of fibrosis when compared to the Hemin group. The expression of pro-inflammatory and pro-fibrotic molecules was significantly higher in the non treated group. Conclusions: The treatment induced the expression of heme oxygenase-1, preventing the installation of fibrosis and even limiting its progression. Objetivo: Este estudo avaliou a capacidade da heme oxigenase-1 em prevenir ou reverter o quadro de fibrose renal. Metodos: Ratos Sprague-dawley machos foram submetidos a UUO e divididos nos grupos: nao-tratados e Hemin. Avaliou-se a funcao renal, fez-se analise histologica e realizou-se RT-PCR para verificar expressao de heme oxigenase-1, MCP-1, IL1-beta, IL-6, TNF-alfa, COL-I, COL-III, PAI-1 e Fibronectina. Resultados: Houve expressao significativamente maior de heme oxigenase-1 nos animais tratados. O grupo nao tratado apresentou niveis significativamente maiores de proteinuria em relacao ao grupo Hemin. O indice proteina/creatinina urinaria da pelve obstruida tambem foi maior no grupo nao tratado, que apresentou ainda maior albuminuria e maior porcentagem de fibrose em relacao ao grupo Hemin. A expressao de moleculas pro-inflamatorias e pro-fibroticas foi significativamente maior no grupo nao tratado. Conclusoes: O tratamento induziu a expressao de heme oxigenase-1, evitando a instalacao da fibrose e mesmo limitando sua progressao.