Single Dose Safety, Tolerance, and Pharmacokinetics of LY450108, an AMPA Potentiator, in Young Healthy Male Subjects

In this study, we investigated the therapeutic efficacy and potential mechanisms of rhein to mitigate chronic allograft nephropathy (CAN) in rats.Fisher rat donors and Lewis rat recipients were used to establish the CAN model. Thirty rats with transplanted kidneys were randomly divided into two groups: 16 untreated and 14 rhein = treated rats. Five Lewis rat controls underwent removal of their right kidneys. The Intervention group was administered rhein oral solution (100 mg kg-1 d-1) by gavage after transplantation. The untreated and control groups were given 0.5% sodium carboxymethyl cellulose. Blood and urine samples were collected at 4, 8, and 16 weeks to examine renal function and total urine protein. Half of the rats in each group were sacrifice at 8 or 16 weeks to examine renal pathology. Immunohistochemical examination and real-time polymerase chain reaction of renal tissues were performed to detect expressions of transforming growth-β1(TGF-β1), hepatic growth factor (HGF), bone morphogenetic protein 7 (BMP7), frobronectin, and collgen IV.Rhein improved renal function and significantly reduced renal fibrosis and interstitial inflammation. The levels of BMP7 and HGF were significantly elevated in the renal tissues of the rhein intervention group. In the meantime, fibronectin and collagen IV were decreased in the extracellular matrix. The expression of TGF-β1 was similar between these two groups.Rhein improved renal function and reduced renal fibrosis and interstitial inflammation by inducing production of HGF and BMP7.