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Tempol Attenuates Renal Fibrosis in Mice with Unilateral Ureteral Obstruction: The Role of PI3K-Akt-FoxO3a Signaling
Journal of Korean Medical Science ; : 230-237, 2014.
Article in English | WPRIM | ID: wpr-35685
ABSTRACT
This study investigated whether tempol, an anti-oxidant, protects against renal injury by modulating phosphatidylinositol 3-kinase (PI3K)-Akt-Forkhead homeobox O (FoxO) signaling. Mice received unilateral ureteral obstruction (UUO) surgery with or without administration of tempol. We evaluated renal damage, oxidative stress and the expression of PI3K, Akt, FoxO3a and their target molecules including manganese superoxide dismutase (MnSOD), catalase, Bax, and Bcl-2 on day 3 and day 7 after UUO. Tubulointerstitial fibrosis, collagen deposition, alpha-smooth muscle actin-positive area, and F4/80-positive macrophage infiltration were significantly lower in tempol-treated mice compared with control mice. The expression of PI3K, phosphorylated Akt, and phosphorylated FoxO3a markedly decreased in tempol-treated mice compared with control mice. Tempol prominently increased the expressions of MnSOD and catalase, and decreased the production of hydrogen peroxide and lipid peroxidation in the obstructed kidneys. Significantly less apoptosis, a lower ratio of Bax to Bcl-2 expression and fewer apoptotic cells in TUNEL staining, and decreased expression of transforming growth factor-beta1 were observed in the obstructed kidneys from tempol-treated mice compared with those from control mice. Tempol attenuates oxidative stress, inflammation, and fibrosis in the obstructed kidneys of UUO mice, and the modulation of PI3K-Akt-FoxO3a signaling may be involved in this pathogenesis.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Spin Labels / Superoxide Dismutase / Ureteral Obstruction / Severity of Illness Index / Fibrosis / Lipid Peroxidation / Signal Transduction / Collagen / Oxidative Stress Limits: Animals Language: English Journal: Journal of Korean Medical Science Year: 2014 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphorylation / Spin Labels / Superoxide Dismutase / Ureteral Obstruction / Severity of Illness Index / Fibrosis / Lipid Peroxidation / Signal Transduction / Collagen / Oxidative Stress Limits: Animals Language: English Journal: Journal of Korean Medical Science Year: 2014 Type: Article