RESUMEN
Acinetobacter baumannii, a prominent emerging pathogen, is responsible for persistent and recurrent healthcare-associated infections (HAIs). Its bacterial resistance and virulence factors, such as biofilm formation, contribute to its survival in hospital environments. Combination therapy has proven to be an effective approach for controlling these infections; however, antimicrobial resistance and compound toxicity can hinder antimicrobial efficacy. Numerous in vitro studies have demonstrated the synergistic effect of antimicrobials and natural products against multidrug-resistant (MDR) A. baumannii biofilm. Riparin III, a natural alkamide derived from Aniba riparia (Nees) Mez., possesses various biological activities, including significant antimicrobial potential. Nonetheless, no reports are available on the use of this compound in conjunction with conventional antimicrobials. Hence, this study aimed to investigate the inhibition and eradication of A. baumannii MDR biofilm by combining riparin III and colistin, along with potential ultrastructural changes observed in vitro. Clinical isolates of A. baumannii, known for their robust biofilm production, were inhibited, or eradicated in the presence of the riparin III/colistin combination. Furthermore, the combination resulted in several ultrastructural alterations within the biofilm, such as elongated cells and coccus morphology, partial or complete disruption of the biofilm's extracellular matrix, and cells exhibiting cytoplasmic material extravasation. At the synergistic concentrations, the riparin III/colistin combination exhibited a low hemolytic percentage, ranging from 5.74% to 6.19%, exerting inhibitory and eradicating effects on the A. baumannii biofilm, accompanied by notable ultrastructural changes. These findings suggest its potential as a promising alternative for therapeutic purposes.
RESUMEN
Stress is crucially related to the pathophysiology of mood disorders, including depression. Since the effectiveness and number of the current pharmacological options still presents significant limitations, research on new substances is paramount. In rodents, several findings have indicated that corticosterone administration induces the manifestation of behavioral and neurochemical aspects of depression. Recently, riparin III has shown antidepressant-like properties in trials performed on animal models. Thus, our goal was to investigate the effects of riparin III on behavioral tests, monoamines levels, oxidative stress and cytokines levels in chronic corticosterone-induced model of depression. To do this, female swiss mice were treated with subcutaneous administration of corticosterone for 22 days. In addition, for the last 10 days, riparin III or fluvoxamine were also administered per os in specific test groups. Control groups received subcutaneous saline injections or distilled water per os. At the end of the timeline, the animals were killed and their hippocampi, prefrontal cortex, and striatum dissected for neurochemical analysis. Brain changes following corticosterone administration were confirmed, and riparin III could reversed the most abnormal behavioral and neurochemical corticosterone-induced alterations. These results suggest the potential antioxidant, anti-inflammatory and antidepressant effects of riparin III after a chronic stress exposure.
Asunto(s)
Depresión , Preparaciones Farmacéuticas , Animales , Conducta Animal , Benzamidas , Corticosterona , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Ratones , Tiramina/análogos & derivadosRESUMEN
Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone-induced chronic depression model. Swiss female mice, 22-25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+ vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one-way anova, followed by Newman-Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders.