Chronic alcohol feeding induces biochemical, histological, and functional alterations in rat retina.

AIMS: Ethanol consumption originates a wide spectrum of disorders, including alteration of visual function. Oxidative stress is included among the mechanisms by which alcohol predisposes nervous tissue to injury. Retina, which is the neurosensorial eye tissue, is particularly sensitive to oxidative stress. METHODS: In this study we analyze the effect of long-term alcohol consumption on oxidative stress parameters of the rat retina, and its correlation to retinal function, as well as to the expression of the antiapoptotic protein Bcl-2. We also study the protective effect of ebselen, a synthetic selenoorganic antioxidant. RESULTS: Herein we show that ethanol has a toxic effect on rat retina associated with oxidative stress. Decreases in retina glutathione concentration and increases in malondialdehyde content in whole eye homogenate significantly correlate with ERG b-wave decrease and Bcl-2 overexpression. We also show how ebselen is able to prevent all the alterations observed. CONCLUSION: Chronic ethanol consumption induces oxidative stress in rat retina associated with an impairment of ERG and Bcl-2 overexpression, suggesting a role for glial cells. All these alterations in the rat allow the proposal of an alcoholic retinopathy in this species.

Ebselen prevents chronic alcohol-induced rat hippocampal stress and functional impairment.

BACKGROUND: Most of the previously published data suggest a role for oxidative or nitrosative stress in ethanol-induced nervous system damage. Moreover, ethanol is able to impair learning abilities in adult mammalian brain, a process suggested to be directly related to hippocampal neurogenesis. Ebselen, a synthetic compound with antioxidant properties, is able to prevent ethanol-induced impairment of neurogenesis in adult rats. The aim of the present work was to further demonstrate the ability of ebselen to prevent biochemical alterations, and preserve long-term potentiation (LTP) and learning abilities, in the hippocampus of chronic alcoholic adult rats. METHODS: Biochemical markers of oxidative stress (glutathione and malondialdehyde) were assayed in hippocampi of control rats and animals fed a liquid alcoholic diet (Lieber-De Carli) supplemented or not with ebselen. Long-term potentiation and hippocampal-dependent tests were studied in all animal groups. RESULTS: The hippocampal concentrations of glutathione and malondialdehyde were decreased and increased, respectively, in alcohol-treated animals, and did not differ from those of the control and the alcohol+ebselen groups. Long-term potentiation in hippocampal slices from ethanol-treated animals was prevented, when compared with controls, and occurred with a similar profile in control animals and in the alcohol+ebselen groups. Learning ability was tested with the Morris water maze test. Escape latencies were higher in ethanol-treated rats than in control animals or the ones treated with ethanol+ebselen. CONCLUSIONS: The results herein strongly suggest that oxidative mechanisms may underlie the hippocampal effects of ethanol in adult rats, in view of the protective effect of ebselen.

Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory activity of the synthetic antioxidant ebselen.

This study was aimed at examining the role of oxygen and nitrogen reactive species in a model of experimental uveitis upon intravitreal injection of bacterial endotoxin to albino New Zealand rabbits. The inflammatory response was evaluated in terms of: (i) the integrity of the blood aqueous barrier (protein and cell content in samples of aqueous humor), (ii) histopathological changes of the eyes, (iii) clinical evaluation (with a score index based on clinical symptoms), and (iv) the concentration of malondialdehyde (MDA), in aqueous humor, as a marker of oxidative stress. Betamethasone was used as reference treatment, superoxide dismutase as quencher of superoxide anion, L-N(G)-nitro-L-arginine-methyl-esther (L-NAME) and chlorpromazine as nitric oxide synthase inhibitors, and ebselen, a glutathione peroxidase mimic, as peroxynitrite reductant. All the substances were injected subconjunctivally to the rabbits immediately after the intravitreal endotoxin injection. Ebselen was the only treatment able to decrease MDA concentration to control values, exerting an effect similar to that elicited by L-NAME on the rest of the parameters tested. The data presented render ebselen a notable choice for the treatment of uveitis, with implications for clinical trials.

Serum malondialdehyde correlates with therapeutic efficiency of high activity antiretroviral therapies (HAART) in HIV-1 infected children.

Serum malondialdehyde (MDA) levels are increased in human immunodeficiency virus (HIV)-infected children, as it happens also in infected adult individuals. Introduction of high activity antiretroviral therapy (HAART) has promoted an intense decline in morbidity and mortality of these patients. Here we present data on the effect of HAART on serum MDA of HIV+ children and compare them with levels prior to HAART. MDA levels reflect, as other markers do, the HAART-induced clinical improvement and probably also the pro-oxidant/antioxidant side effects of the different drugs used. The results herein allow the proposal of including serum MDA levels as an additional parameter for the clinical management of HIV+ children.