RESUMO
Alcohol is a severe hepatotoxicant that causes a variety of liver disorders. Rosmarinic acid (RA), a natural phenol, shows some biological activities, including antioxidant and anti-inflammatory effects. We investigated the effects of RA (10 mg/kg) against ethanol-induced oxidative damage and hepatotoxicity in rats. Animals received ethanol (4 g/kg, i.g.) and (or) RA (10 mg/kg, i.g.) daily for 4 weeks. At the end of the treatment period, rats were weighed and use for biochemical, molecular, and histopathological examinations. Ethanol increased hepatic lipid peroxidation (P < 0.001) and decreased hepatic levels of reduced glutathione (P < 0.01), catalase (P < 0.05), and superoxide dismutase (P < 0.001) compared with control group. RA prevented the prooxidant and antioxidant imbalance induced by ethanol in liver. Furthermore, RA ameliorated the increased liver mass, serum levels of ALT, AST, LDH, TNF-α, and IL-6 in ethanol group. Necrosis and infiltration of inflammatory cells in liver parenchyma were attenuated by RA treatment. Our findings showed that RA prevents ethanol-induced oxidant/antioxidant imbalance and liver injury in an experimental model of ethanol-induced hepatotoxicity. Therefore, RA may be a good candidate to protect against ethanol-induced hepatotoxicity; this deserves consideration and further examination.
Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Etanol/toxicidade , Fígado/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Cinamatos/administração & dosagem , Citocinas/sangue , Depsídeos/administração & dosagem , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Inclusão em Parafina , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangue , Ácido RosmarínicoRESUMO
OBJECTIVES: Ethanol consumption induces neurological disorders including cognitive dysfunction. Oxidative damage is considered a likely cause of cognitive deficits. We aimed to investigate the effects of rosmarinic acid (RA) in different doses for 30 days on chronic ethanol-induced cognitive dysfunction using the passive avoidance learning (PAL) and memory task in comparison with donepezil, a reference drug. We also evaluated the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation in hippocampus as possible mechanisms. METHODS: Memory impairment was induced by 15%â w/v ethanol (2 g/kg, i.g.) administration for 30 days. RA (8, 16, and 32â mg/kg, i.g.) or donepezil (2â mg/kg, i.g.) was administered 30 minutes before ethanol. The acquisition trial was done 1â hour after the last administration of RA and donepezil. At the end, animals were weighed and hippocami were isolated for analyzing of oxidant/antioxidant markers. RESULTS: Ethanol caused cognition deficits in the PAL and memory task. While RA 16 and 32â mg/kg improved cognition in control rats, it prevented learning and memory deficits of alcoholic groups. RA 8â mg/kg did not influence cognitive function in both control and alcoholic rats. RA 32â mg/kg had comparable effects with donepezil in prevention of acquisition and retention memory impairment. The higher doses of RA not only prevented increased lipid peroxidation and nitrite content but also decreased SOD, CAT, GSH, and FRAP levels in alcoholic groups and exerted antioxidant effects in non-alcoholic rats. DISCUSSION: We showed that RA administration dose-dependently prevented cognitive impairment induced by chronic ethanol in PAL and memory and disturbed oxidant/antioxidant status as a possible mechanism. The antioxidant, anticholinesterase, and neuroprotective properties of RA may be involved in the observed effects. Therefore, RA represents a potential therapeutic option against chronic ethanol-induced amnesia which deserves consideration and further examination.