Development of nobel pharmacological treatment to inhibit renal fibrosis caused by unilateral ureteral obstruction

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Introduction and Objective: We focused on the effect of alpha-lipoic acid (ALA) on renal injury caused by unilateral ureteral obstruction (UUO). Reactive oxygen species (ROS) is reportedly generated in UUO and oxidative stress caused by ROS results in irreversible renal damage including interstitial fibrosis and tubular apoptosis. Thus agents that decrease oxidative stress are potential effective tools for the treatment of UUO. ALA is an antioxidant and its renoprotective effects have been shown in several renal disease models such as glomeronephritis and diabetic nephropathy. The present study was undertaken to evaluate the effects of ALA on mediator of renal injury, TGF-β1, and parameters of renal injury in a rat UUO model. Methods: Two groups of Sprague-Dawley rats were subject to left UUO. Group 1: control (oral administration of 0.5% carboxylmethyl cellulose beginning 1 days prior to UUO and continuing throughout study, n=10). Group 2: ALA treatment (oral administration of ALA in … More 0.5% carboxylmethyl cellulose beginning 1 days prior to UUO and continuing throughout study, n=10). Kidneys were harvested at day 14 after UUO. The following was examined: interstitial fibrosis, point counting of Masson's trichrome-stained slides and fibroblast specific protein (FSP) immunostaining; macrophage infiltration, ED-1 immunostaining; apoptosis, ssDNA immunostaining; TGF-β1, ELISA. Results: Interstitial fibrosis in obstructed kidney was significantly decreased in ALA group compared to control group (See table). Tissue TGF-β levels were significantly lower in ALA group compared to control group (See table), suggesting that the decline in TGF-β level in the kidney was one of causes for the improvement of renal injury by ALA treatment. Apoptotic cells in obstructed kidney were significantly decreased by ALA treatment. In contrast, there was no significant difference in the number of infiltrated macrophage between control and ALA group. Conclusions: Antioxidant, α-lipoic acid, decreases tissue TGF-β and improved tubular apoptosis and renal fibrosis but not macrophage infiltration in UUO. Alfa-lipoic acid may be a clinically useful agent for the treatment of UUO. Less