ABSTRACT
Abstract Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid Reactive Substances (TBARS) and reduced glutathione (GSH). The evaluation of cell death and the mitochondrial depolarization were analyzed by flow cytometry. Quercetin prevents cell death reducing oxidative stress and preventing mitochondrial membrane depolarization. Molecular docking showed that quercetin prevents cell damage better than losartan and lisinopril, inhibitors of RAS. Quercetin has a potential to interact with type 1 angiotensin II receptor (AT1) with greater affinity through the formation of five hydrogen bonds of strong intensity.
ABSTRACT
A Organização Mundial de Saúde estima que aproximadamente 7 a 8 milhões de pessoas encontram-se infectadas pelo Trypanosoma cruzi no mundo. O tratamento da doença de Chagas apresenta eficácia limitada e efeitos colaterais que limitam a tolerabilidade e a adesão dos pacientes. A busca de novas alternativas terapêuticas a partir de substâncias bioativas cresceu bastante nos últimos anos. A violaceína (VIO), um pigmento bacteriano produzido por Chromobacterium violace um tem mostrado diversas ações biológicas, dentre elas, ações antiulcerogênica, antitumoral, antiviral e antiparasitária. No presente trabalho, estudamos os efeitos da VIO sobre as formas evolutivas doTrypanosoma cruzi. As formas epimastigotas foram cultivadas em meio LIT, a 28°C, na presença deVIO (0,97; 1,9; 3,9; 7,8; 15,62; 31,25; 62,5; 125; 250; 500; 1000μM) por 24, 48 e 72h. As formas tripomastigotas, foram obtidas após infecção em células LLC-MK2, ressuspensas em meio DMEM2% de SBF e incubadas com VIO (0,97; 1,9; 3,9; 7,8; 15,62; 31,25μM) por 24h. Formas amastigotas foram cultivadas em lamínulas circulares no interior de placas de cultura contendo células LLC-MK2e tratadas com violaceína (4,97 e 9,94 μM)...
The World Health Organization estimates that approximately 7 to 8 million individuals areinfected with Trypanosoma cruzi worldwide. The treatment of Chagas disease has limited efficacy andside effects that limit patient tolerability and compliance. The search for new therapeutic alternativesbased on bioactive substances has increased significantly in recent years. Violacein (VIO), a bacterialpigment produced by Chromobacterium violaceum, has shown several biological actions and amongthem, antiulcer, antitumor, antiviral, and antiparasitic action. In this study, we assessed the effects ofVIO on the evolutionary forms of Trypanosoma cruzi. Epimastigotes were cultured in liver infusiontryptose (LIT) medium at 28 °C in the presence of VIO (0.97; 1.9; 3.9; 7.8; 15.62; 31.25; 62.5; 125;250 ; 500; 1000μM) for 24, 48 and 72 hours. Trypomastigotes were obtained after infection in LLCMK2cells resuspended in 2% DMEM medium of FBS and incubated with VIO (0.97; 1.9; 3.9; 7.8;15.62; 31.25μM ) for 24h. Amastigotes were cultured on circular glass slides within culture platescontaining LLC-MK2 cells and treated with violacein (4.97 and 9.94 μM)...