RUBOXISTAURIN AMELIORATES DIABETIC KIDNEY DISEASE IN RATS THROUGH INHIBITION OF TRANSCRIPTION NUCLEAR FACTOR-KAPPA B/P65 (NF-KB/P65)
Aly Mohamed Ahmed
Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Department of Histology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Background: Current therapeutic approaches are only moderately efficacious at preventing the progression of diabetic kidney disease (DKD). DKD is the most frequent cause of end-stage renal disease (ESRD) worldwide. Successful development of novel effective therapies for DKD is essential to reverse this trend. Ruboxistaurin (RBX), a protein kinase Cβ (PKC-β) specific inhibitor, significantly decreased albuminuria and stabilized kidney function in patients with diabetic kidney disease. Objective: The purpose of this study was to evaluate the potential protective effect of ruboxistaurin on the kidney in diabetic kidney disease through the inhibition of NF-kB/p65 activation. Material and Methods: Thirty adult male Wistar rats were allocated into three groups: control group, untreated diabetic group and RBX-treated-diabetic group. Diabetes was induced by a single intrapeitoneal injection of streptozotocin (55 mg/kg). RBX-treated diabetic rats were treated orally with RBX (10 mg/kg/day) for 6 weeks. At the end of the experiment, all rats were sacrificed and the trunkal blood samples were collected to measure the serum levels of glucose, creatinine and urea, and the right kidneys were excised and processed for histopathological and immunohistochemical studies. Results: Untreated diabetes induced severe glomerulosclerosis, mesangial expansion and necrosis, and loss of numerous renal tubular epithelial cells that were markedly ameliorated by ruboxistaurin treatment. Also, increased deposition of collagen fibers in the renal interstitium was detected in untreated diabetic rats and was obviously attenuated by ruboxistaurin administration. In addition, untreated diabetes induced strong positive immunostaining for NF-kB/p65 expression, mainly in the nuclei and cytoplasm of numerous renal tubular epithelial cells, that was inhibited by ruboxistaurin treatment. Conclusion: The results of the present study indicated that ruboxistaurin treatment ameliorated the development of diabetic kidney disease through its inhibitory effect on the NF-kB/p65 pathway in diabetic rat kidney; therefore, it could be a potential therapeutic agent for treatment of diabetic kidney disease.