RESUMEN
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.
Asunto(s)
Antidepresivos/farmacología , Benzamidas/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Hipocampo/metabolismo , Tiramina/análogos & derivados , Anhedonia/efectos de los fármacos , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Conducta Animal/efectos de los fármacos , Corticosterona/farmacología , Depresión/inducido químicamente , Depresión/psicología , Femenino , Fluvoxamina/farmacología , Suspensión Trasera/psicología , Hipocampo/efectos de los fármacos , Relaciones Interpersonales , Ratones , Actividad Motora/efectos de los fármacos , Natación/psicología , Tiramina/farmacologíaRESUMEN
Nephrotoxicity is the main complication of gentamicin (GM) treatment. GM induces renal damage by overproduction of reactive oxygen species and inflammation in proximal tubular cells. Phenolic compounds from ginger, called gingerols, have been demonstrated to have antioxidant and anti-inflammatory effects. We investigated if oral treatment with an enriched solution of gingerols (GF) would promote a nephroprotective effect in an animal nephropathy model. The following six groups of male Wistar rats were studied: (i) control group (CT group); (ii) gingerol solution control group (GF group); (iii) gentamicin treatment group (GM group), receiving 100 mg/kg of body weight intraperitoneally (i.p.); and (iv to vi) gentamicin groups also receiving GF, at doses of 6.25, 12.5, and 25 mg/kg, respectively (GM+GF groups). Animals from the GM group had a significant decrease in creatinine clearance and higher levels of urinary protein excretion. This was associated with markers of oxidative stress and nitric oxide production. Also, there were increases of the mRNA levels for proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1ß [IL-1ß], IL-2, and gamma interferon [IFN-γ]). Histopathological findings of tubular degeneration and inflammatory cell infiltration reinforced GM-induced nephrotoxicity. All these alterations were attenuated by previous oral treatment with GF. Animals from the GM+GF groups showed amelioration in renal function parameters and reduced lipid peroxidation and nitrosative stress, in addition to an increment in the levels of glutathione (GSH) and superoxide dismutase (SOD) activity. Gingerols also promoted significant reductions in mRNA transcription for TNF-α, IL-2, and IFN-γ. These effects were dose dependent. These results demonstrate that GF promotes a nephroprotective effect on GM-mediated nephropathy by oxidative stress, inflammatory processes, and renal dysfunction.