RESUMO
Exposure to aluminum (Al) and aluminumâ¯+â¯manganese (Mn) can trigger an increase in reactive oxygen species (ROS) and modify the activity of oxidative defense enzymes. This study investigated whether exposure to Al and Alâ¯+â¯Mn at acid pH for 24 and 96â¯h causes oxidative stress evidenced by antioxidants and oxidative damage in the gills and liver of sexually mature Astyanax altiparanae males. The fish were subsequently immersed in metal-free water for 24 and 96â¯h to see whether they recovered from the effects of these metals. Exposure to an acid pH boosted the activity of gill superoxide dismutase (SOD) at 96â¯h and the fish did not recover when immersed for the same period in water at neutral pH. Exposure to Al increased glutathione (GSH) levels (24â¯h) in the gills, returning to control levels during the recovery period, showing the efficiency of the antioxidant system in preventing lipid peroxidation of the gills and liver. Mn did not modify the activity of the enzymes studied, but did trigger late hepatic lipid peroxidation during the recovery period. The group exposed to Alâ¯+â¯Mn exhibited several alterations, including increased concentration of GSH, as well as higher GPx and GR activity in the gills. Despite the defensive responses triggered by acute exposure, during the recovery period there were alterations in catalase (96â¯h) and an increase in hepatic metallothionein (24â¯h), but this did not prevent hepatic lipid peroxidation. Al and Alâ¯+â¯Mn produced different effects, and the timing of enzymatic and non-enzymatic antioxidant defenses also differed.
Assuntos
Alumínio/toxicidade , Characidae/fisiologia , Brânquias/efeitos dos fármacos , Fígado/efeitos dos fármacos , Manganês/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluição Química da Água/efeitos adversos , Adaptação Fisiológica , Animais , Catalase/metabolismo , Sinergismo Farmacológico , Proteínas de Peixes/agonistas , Proteínas de Peixes/metabolismo , Brânquias/enzimologia , Brânquias/metabolismo , Glutationa/agonistas , Glutationa/metabolismo , Concentração de Íons de Hidrogênio , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Metalotioneína/metabolismo , Reprodutibilidade dos Testes , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo , Testes de Toxicidade AgudaRESUMO
Quercetin is a known antioxidant and protein kinase C (PKC) inhibitor. Previous studies have shown that mania involves oxidative stress and an increase in PKC activity. We hypothesized that quercetin affects manic symptoms. In the present study, manic-like behavior (hyperlocomotion) and oxidative stress were induced by 24h paradoxical sleep deprivation (PSD) in male Swiss mice. Both 10 and 40mg/kg quercetin prevented PSD-induced hyperlocomotion. Quercetin reversed the PSD-induced decrease in glutathione (GSH) levels in the prefrontal cortex (PFC) and striatum. Quercetin also reversed the PSD-induced increase in lipid peroxidation (LPO) in the PFC, hippocampus, and striatum. Pearson's correlation analysis revealed a negative correlation between locomotor activity and GSH in the PFC in sleep-deprived mice and a positive correlation between locomotor activity and LPO in the PFC and striatum in sleep-deprived mice. These results suggest that quercetin exerts an antimanic-like effect at doses that do not impair spontaneous locomotor activity, and the antioxidant action of quercetin might contribute to its antimanic-like effects.
Assuntos
Antimaníacos/farmacologia , Antioxidantes/farmacologia , Transtorno Bipolar/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Agitação Psicomotora/tratamento farmacológico , Quercetina/farmacologia , Animais , Transtorno Bipolar/etiologia , Transtorno Bipolar/metabolismo , Transtorno Bipolar/fisiopatologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Esquema de Medicação , Glutationa/agonistas , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Agitação Psicomotora/etiologia , Agitação Psicomotora/metabolismo , Agitação Psicomotora/fisiopatologia , Privação do Sono/complicações , Privação do Sono/metabolismo , Privação do Sono/fisiopatologiaRESUMO
Astrocytes play an essential role in the central nervous system (CNS) homeostasis. They providing metabolic support and protecting against oxidative stress and glutamatergic excitotoxicity. Glutamate uptake, an electrogenic function, is driven by cation gradients and the Naâº-Kâº-Clâ» co-transporter (NKCC1) carries these ions into and out of the cell. Elevated concentrations of ammonia in the brain lead to cerebral dysfunction. Ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and ion discharged. Astrocytes also convert excess ammonia and glutamate into glutamine, via glutamine synthetase (GS). Lipoic acid (LA) is a modulator of the cellular redox status potentially beneficial in neurodegenerative diseases. In this study, we investigated the effect of LA on glial parameters, in C6 cells exposed to ammonia. Ammonia increased S100B secretion and decreased glutamate uptake, GS activity and glutathione (GSH) content. LA was able to prevent these effects. LA exerts its protective effect on glutamate uptake and S100B secretion via mechanisms dependent of NKCC1 and PKC. These findings show that LA is able to modulate glial function impairments by ammonia in vitro, indicating a potential therapeutic agent to improve glutamatergic metabolism and oxidative stress against hyperammonemia.