RESUMO
Background: Diabetic nephropathy (DN) is a critical complication of diabetes mellitus. This study evaluates whether administration of conditioned medium from kidney tubular cells (KTCs-CM) has the ability to be efficacious as an alternative to cell-based therapy for DN. Materials and Methods: CM of rabbit kidney tubular cells (RK13; KTCs) has been collected and after centrifugation, filtered with 0.2 filters. Four groups of rats have been utilized, including control, DN, DN treated with CM, and sham group. After diabetes induction by streptozotocin (50 mg/kg body weight) in rats, 0.8 ml of the CM was injected to each rat three times per day for 3 consecutive days. Then, 24-h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) have been measured through detection kits. The histopathological effects of CM on kidneys were evaluated by periodic acid-Schiff staining and the expression of microRNAs (miRNAs) 29a and 377 by using the real-time polymerase chain reaction. The expression of aquapurin-1 (AQP1) protein was also examined by Western blotting. Results: Intravenous injections of KTCs-CM significantly reduced the urine volume, protein 24-h, BUN, and Scr, decreased the miRNA-377, and increased miRNA-29a and AQP1 in DN treated with CM rats. Conclusion: KTCs-CM may have the potential to prevent kidney injury from diabetes by regulating the microRNAs related to DN and improving the expression of AQP1.
RESUMO
This work aims to evaluate the renoprotective effect of luteolin on expression of Nrf2 and miR320 in ischemia-reperfusion (I/R) injury in rats. Thirty rats were randomly divided into five groups; control, Luteolin (50 mg/kg), ischemia-reperfusion (I/R), DMSO (0/1%) + I/R and Luteolin+I/R, (n = 6 each). Administration of luteolin and DMSO was carried out by gavage for 3 days before renal I/R. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 2 h. All rats were killed and the renal function, histological changes, oxidative stress degree, in all of groups were evaluated. In addition, the effects of luteolin on renal expression of Nrf2 and miR320 were examined by immunohistochemistry and real time- PCR. Luteolin significantly improved the creatinine (Cr) and blood urea nitrogen (BUN) levels in Luteolin + I/R group compared to I/R group (p < 0.001 and p < 0.001 respectively). Reduction of enzymatic activity of superoxide dismutase, glutathione peroxidase and catalase in I/R and DMSO + I/R groups, was significantly improved by Luteolin (p < 0.05) in Luteolin + I/R group. Pre-treatment with luteolin also resulted in significant reduction in tissue MDA level (p < 0.001), Nrf2 (p < 0.001) and miR320 expression (P < 0.05) that were increased by renal I/R. Also, the rats pretreated with luteolin had nearly normal structure of the kidney. These results indicate that luteolin protects the kidney against I/R injury via reducing oxidative stress, increasing antioxidant enzymes and reducing expression of Nrf2 and miR320.