MON-218 Protective role of TV-induced autophagy in an in vivo model of unilateral ureteral obstruction-induced renal cell injury

Abstract

Toxicodendron vernicifluum is used as a traditional herbal medicine in Asia. The physiological properties and antioxidative effects of Toxicodendron vernicifluum extract (TV) have been demonstrated in several experimental studies. Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to obstructive nephropathy. Toxicodendron vernicifluum is used as a traditional herbal medicine in Asia. The physiological properties and antioxidative effects of Toxicodendron vernicifluum extract (TV) have been demonstrated in several experimental studies. Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to obstructive nephropathy. Oxidative stress resulting from UUO may be aggravated by increased ROS production. Furthermore, oxidative stress may induce renal apoptosis and contribute to the pathogenesis of kidney disease caused by UUO. This study evaluated the possible renoprotective effects of TV on UUO-induced tubular damage, as well as the mechanism through which it exerts antioxidative and anti-apoptotic effects against UUO-induced cell death. Male Sprague–Dawley rats weighing 180–200 g each were assigned to one of two groups. The first group (UUO+TV) of rats drank TV for 2 weeks before surgery. The second group (UUO) of rats drank water for 2 weeks. Three days later, a morphologic evaluation of renal injury was conducted using hematoxylin and eosin and TUNEL staining. The renal protein expression of PCNA, caspase-3, Nrf2, catalase, and phosphorylated p38 as markers of autophagy was determined by immunoblotting. Obstruction injury caused marked apoptosis and oxidative stress in the UUO group. It also increased the level of phosphorylated p38 and decreased the level of PCNA, suggesting delayed recovery from damage. The number of TUNEL-positive cells, which were detected based on DNA fragmentation, was increased in the UUO group. Notably, there was a significant relationship with increased expression of cleaved caspase-3, which was counteracted by TV treatment. Moreover, a comparison with the UUO group revealed that TV significantly enhanced the regulation of autophagy and autophagic flux. Taken together, our findings suggest that the induction of autophagy protects against UUO-induced apoptotic damage via ROS and a p38-regulated pathway in this in vivo model. TV-induced autophagy may be a useful target for therapeutic intervention in ischemia-reperfusion renal injury.