SP320OXIDATIVE/NITRATIVE STRESS AND INFLAMMATION DRIVE PROGRESSION OF DOXORUBICIN-INDUCED RENAL FIBROSIS IN RATS AS REVEALED BY COMPARING A NORMAL AND A FIBROSIS-RESISTANT RAT STRAIN

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Introduction and Aims: Genetic background has a strong influence on the progression of chronic kidney disease. We recently found that Rowett black hooded rats were resistant to renal fibrosis. We aimed to investigate the role of sustained inflammation and oxidative/nitrative damage in renal fibrosis progression using this new model. Our previous data suggested the involvement of podocytes, thus we investigated renal fibrosis initiated by doxorubicin-induced podocyte damage. Methods: Rats were treated with Doxorubicin (5 mg/kg) and observed for 8-weeks. Survival was assessed in a separate cohort. Renal function was assessed as urinary protein and neutrophil gelatinase-associated lipocalin excretion and histologic analysis following periodic acid-Schiff and Picro-Sirius-red staining and nephrin and fibronectin immunohistochemistry and profibrotic factors (TGF-β1, CTGF, collagen type I alpha 1), and inflammatory (MCP1) mRNA expression were detected by PCR. Oxidative and nitrative stress was evaluated by p47phox (neutrophil cytosol factor 1) p91-phox (NADPH oxidase-2) expression on western blot and 4-hydroxynonenal (HNE) and nitrotyrosine (NT) staining.

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