RESUMO
PURPOSE: Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. METHODS: In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. RESULTS: Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. CONCLUSIONS: Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Elipticinas , Ratos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico , Elipticinas/metabolismo , Elipticinas/farmacologia , Elipticinas/uso terapêutico , Rim , Estresse Oxidativo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Peso Corporal , Diabetes Mellitus/metabolismoRESUMO
Despite DNA being an important target for several drugs, most of the docking programs are validated only for proteins and their ligands. In this paper, we used AutoDock 4.0 to perform self-dockings and cross dockings between two DNA ligands (a minor groove binder and an intercalator) and four distinct receptors: 1) crystallographic DNA without intercalation gap; 2) crystallographic DNA with intercalation gap; 3) canonical B-DNA; and 4) modified B-DNA with intercalation gap. Besides being efficient in self-dockings, AutoDock is capable of correctly identifying two of the main DNA binding modes with the condition that the target possesses an artificial intercalation gap. Therefore, we suggest a default protocol to identify DNA binding modes which uses a modified canonical DNA (with gap) as receptor. This protocol was applied to dock two different Troger bases to DNA and the predicted binding modes agree with those suggested, yet not established, by experimental data. We also applied the protocol to dock aflatoxin B(1) exo-8,9-epoxide, and the results are in complete agreement with experimental data from the literature. We propose that this approach can be used to investigate other ligands whose binding mode to DNA remains unknown, yielding a suitable starting point for further theoretical studies such as molecular dynamics simulations.