RESUMEN
We tested the hypothesis that administration of omega (ω)-9, ω-3, and ω-6 to mice can prevent oxidative alterations responsible for behavioral and cognitive alterations related with aging. Twenty-eight-day-old mice received skim milk (SM group), SM enriched with omega oil mixture (EM group), or water (control group) for 10 and 14 months, equivalent to middle age. Mice were evaluated for behavioral alterations related to depression and memory and oxidative status [brain levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and myeloperoxidase (MPO)]. The 10-month EM group increased immobility time during the forced swimming test compared with control, indicating increased stress response. The 14-month SM- and EM-treated groups increased sucrose consumption compared with control, showing an expanded motivational state. The 14-month SM group decreased the number of rearings compared with the 14-month control and EM groups. The number of entries and time spent in the central square of the open field was higher in the 10-month EM group than in the control, revealing an anxiolytic-like behavior. TBARS decreased in the hippocampus and striatum of the 10-month EM group compared with the control. A similar decrease was observed in the striatum of the 10-month SM group. GSH levels were higher in all 14-month treated groups compared with 10-month groups. MPO activity was higher in the 14-month EM group compared with the 14-month control and SM groups, revealing a possible pro-inflammatory status. In conclusion, omega oils induced conflicting alterations in middle-aged mice, contributing to enhanced behavior and anxiolytic and expanded motivational state, but also to increased stress response and pro-inflammatory alterations.
Asunto(s)
Ansiolíticos , Ácidos Grasos Omega-3 , Animales , Ratones , Masculino , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Peroxidasa , Ansiolíticos/farmacología , Leche/química , Leche/metabolismo , Estrés Oxidativo , Ácidos Grasos Omega-3/farmacología , Glutatión/metabolismo , Sacarosa/farmacología , AguaRESUMEN
We tested the hypothesis that administration of omega (ω)-9, ω-3, and ω-6 to mice can prevent oxidative alterations responsible for behavioral and cognitive alterations related with aging. Twenty-eight-day-old mice received skim milk (SM group), SM enriched with omega oil mixture (EM group), or water (control group) for 10 and 14 months, equivalent to middle age. Mice were evaluated for behavioral alterations related to depression and memory and oxidative status [brain levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and myeloperoxidase (MPO)]. The 10-month EM group increased immobility time during the forced swimming test compared with control, indicating increased stress response. The 14-month SM- and EM-treated groups increased sucrose consumption compared with control, showing an expanded motivational state. The 14-month SM group decreased the number of rearings compared with the 14-month control and EM groups. The number of entries and time spent in the central square of the open field was higher in the 10-month EM group than in the control, revealing an anxiolytic-like behavior. TBARS decreased in the hippocampus and striatum of the 10-month EM group compared with the control. A similar decrease was observed in the striatum of the 10-month SM group. GSH levels were higher in all 14-month treated groups compared with 10-month groups. MPO activity was higher in the 14-month EM group compared with the 14-month control and SM groups, revealing a possible pro-inflammatory status. In conclusion, omega oils induced conflicting alterations in middle-aged mice, contributing to enhanced behavior and anxiolytic and expanded motivational state, but also to increased stress response and pro-inflammatory alterations.
RESUMEN
BACKGROUND: Ischemia/reperfusion injury during liver transplantation can cause severe damage to the graft. The objective of this randomized, double-blind study was to evaluate the possible protective effects of L-alanyl-glutamine on the liver graft. METHODS: The sample included 33 patients from a liver transplantation service in Northeastern Brazil. Before cold ischemia, the patients received 50 g of L-alanyl-glutamine (treatment group) or saline (control group) through the portal vein. The graft was biopsied at the time of recovery, at the beginning of warm ischemia, and at the end of transplantation to determine malondialdehyde (MDA), heat-shock protein (Hsp)70, nuclear factor kappa-beta (NFkB), superoxide dismutase (SOD), and reduced glutathione (GSH) levels. RESULTS: The blood parameters were similar in the two groups. In the treatment group, MDA did not increase at the beginning of cold ischemia and decreased at the end of transplantation. This phenomenon was not observed in the control group. GSH, SOD, Hsp70, and NFkB levels were similar in the two groups. CONCLUSIONS: Our findings suggest that preconditioning with L-alanyl-glutamine attenuates the effects of ischemia/reperfusion-related oxidative stress and reduces lipid peroxidation in the grafts of liver transplantation patients.
Asunto(s)
Dipéptidos/farmacología , Trasplante de Hígado/métodos , Estrés Oxidativo/efectos de los fármacos , Adolescente , Adulto , Anciano , Brasil , Niño , Isquemia Fría , Método Doble Ciego , Femenino , Glutatión/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacos , Trasplante de Hígado/efectos adversos , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , FN-kappa B/metabolismo , Estudios Prospectivos , Daño por Reperfusión/etiología , Superóxido Dismutasa/metabolismo , Isquemia Tibia , Adulto JovenRESUMEN
To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K+ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs-Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (approximately 50%) in HCC strips precontracted with K+ 40 mM. This effect was not blocked by tetrodotoxin (1 microM) (54.6+/-4.6 vs 48.9+/-6.4%) or (atropine (10 microM) (52.7+/-6.5 vs 58.6+/-5.6%). However, this relaxation was significantly attenuated by L-NAME (100 microM) (59.7+/-5.8 vs 27.8+/-7.1%; P<0.05; n = 8) and ODQ (100 microM) (62.7+/-5.1 vs 26.8+/-3.9%; P<0.05; n = 8). Charybdotoxin and apamin (K(Ca)-channel blockers) did not affect the phentolamine relaxations (54.6+/-4.6 vs 59.3+/-5.2%). Glibenclamide (100 microM), an inhibitor of K(ATP)-channel, caused a significant inhibition (56.7+/-6.3 vs 11.3+/-2.3%; P<0.05; n = 8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.6+/-5.6 vs 5.7+/-1.4%; P<0.05; n = 8). The results suggest that phentolamine relaxes HCC by a nonadrenergic-noncholinergic mechanism dependent on nitric oxide synthase activity and activation of K(ATP)-channel.