RESUMO
Objective: Nephropathy is known to be the leading cause of kidney failure in diabetic patients. Troxerutin, as a flavonoid component, could provide a novel protective strategy in the prevention of diabetic nephropathy. A large number of reports on the salutary effects of troxerutin inspired us to investigate its effect on the nephropathy signaling events (i.e., expression of TGF-ß, miRNA192, and SIP1) in type-1 induced diabetic rats. Materials and Methods: 50 male Wistar rats were divided into 5 groups including control group, sham group treated with troxerutin for 4 weeks, diabetic group induced by streptozotocin (STZ) injection, DI group including insulin-treated diabetic animals and DT group treated with troxerutin. Ultimately, rat kidneys were extracted, and the level of miR-192 (using qPCR), transforming growth factor-beta (TGF-ß), and smad interacting protein 1 (SIP1) using an ELISA kit, was measured. Results: The level of TGF-ß and miRNA192 significantly increased in the diabetic group. However, their expression levels decreased following the administration of troxerutin and insulin (p<0.05) compared to control group. SIP1 was down-regulated in the diabetic group, whereas a spike in the expression levels was observed after troxerutin administration compared to control and troxerutin groups (p<0.05). However, no significant difference was found in the effects of insulin and troxerutin on the level of miR-192, SIP1, and TGF- ß. Conclusion: According to the previous literatures, during the progression of nephropathy, TGF-ß represses SIP1 (the repression region in the collagen gene) by increasing the expression of miR-192. Ultimately, in this study, diabetes led to up-regulation of TGF-ß while troxerutin proved to have a protective effect on the kidney by increasing SIP and lowering miR-192 levels.
RESUMO
Phencyclidine (PCP, I) and many of its derivatives have demonstrated many pharmacological effects. They interact with a number of neurotransmitter systems within the central nervous system. For example, Phencyclidine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, and it causes the release and inhibits the reuptake of monoaminergic neurotransmitters, including dopamine, serotonin and norepinephrine. In this study, new thienyl (TCP, II), as well as benzothiophen (BTCP, III) derivatives (IV-VII) were synthesized. The acute and chronic pain activities of these drugs were studied using the tail immersion and formalin tests on mice and the results were compared with PCP, TCP and control groups at dosage of 10 mg/kg. The results indicated that the drug VII produced more analgesic effects on acute chemical pain in formalin test compared with other drugs. In addition, this analgesic effect was remarkably seen for drugs II, VI and VII in chronic pain in the mentioned test in comparison with other drugs. Also, the results showed that acute thermal pain could be diminished by drugs VI, II and I compared with other drugs in tail immersion test. It can be concluded that more analgesic effects of new BTCP analogues (VI and VII) may be concerned with antinociception activities of benzothiophene group and also with binding to cocaine site on the dopamine transporter receptor which seems to be more potent than PCP receptor in decreasing pain.
