Oral administration of lutein attenuates ethanol-induced memory deficit in rats by restoration of acetylcholinesterase activity.

The excessive consumption of alcohol affects the central nervous system, resulting in memory and learning deficits. Lutein is a carotenoid known for its antioxidant properties, which can be able to prevent neurodegenerative diseases and cognitive deficits. In the present study, we evaluated the effect of lutein on ethanol-induced memory deficits in the object recognition task in adult rats, as well as the possible involvement of oxidative stress and cholinergic system. Wistar rats were randomly divided into two groups receiving lutein (50 mg/kg) or olive oil (1 mL/kg) by oral gavage once daily for 14 days. On day 8 each group was divided again into two groups receiving either ethanol (3 g/kg) or saline by oral gavage once daily for 7 days. After the last administration, the animals were submitted on the object recognition task 24 h later (on days 15, 16 and 17). After the behavioral test, the hippocampus and cerebral cortex were removed for the determination of oxidative stress indicators (superoxide dismutase, thiobarbituric acid reactive substances, and non-protein thiol) and acetylcholinesterase activity. Ethanol administration induced a memory deficit and increased acetylcholinesterase activity, however, it did not alter the parameters of oxidative stress, evaluated in the cortex and hippocampus. Oral administration of lutein (50 mg/kg during 14 days) attenuated memory deficit and the increase of acetylcholinesterase activity induced by ethanol. These results provide evidence that lutein is an alternative treatment for ethanol-induced memory deficit, and suggest the involvement of cholinergic system.

Methylmalonate Induces Inflammatory and Apoptotic Potential: A Link to Glial Activation and Neurological Dysfunction.

Methylmalonic acid (MMA) accumulates in tissues in methylmalonic acidemia, a heterogeneous group of inherited childhood diseases characterized by neurological dysfunction, oxidative stress and neuroinflammation; it is associated with degeneration of striatal neurons and cerebral cortical atrophy. It is presently unknown, however, whether transient exposure to MMA in the neonatal period is sufficient to trigger inflammatory and apoptotic processes that lead to brain structural damage. Here, newborn mice were given a single intracerebroventricular dose of MMA at 12 hours after birth. Maze testing of 21- and 40-day-old mice showed that MMA-injected animals exhibited deficit in the working memory test but not in the reference test. MMA-injected mice showed increased levels of the reactive oxygen species marker 2',7'-dichlorofluorescein diacetate, tumor necrosis factor, interleukin-1ß, caspases 1, 3, and 8, and increased acetylcholinesterase activity in the cortex, hippocampus and striatum. This was associated with increased astrocyte and microglial immunoreactivity in all brain regions. These findings suggest that transient exposure to MMA may alter the redox state and cause neuroinflammatory/apoptotic processes and glial activation during critical periods of brain development. Similar processes may underlie brain dysfunction and cognitive impairment in patients with methylmalonic acidemia.

Antinociceptive and anti-inflammatory effect of the Scutia buxifolia Reissek stem barks extract.

BACKGROUND: Scutia buxifolia (Rhamnaceae) has been extensively studied for its phenolics groups, which are able to capture free radicals; being therefore, considered promising as an antioxidant in preventing diseases resulting from oxidative stress. HYPOTHESIS: Scutia buxifolia extract (SBE) presents antinociceptive and anti-inflammatory effect in mice. STUDY DESIGN: SBE (400-800mg/kg) was tested in different pain models to investigate its antinociceptive and anti-inflammatory action. METHODS: It was carried out the abdominal writhing test, capsaicin test, thermal hyperalgesia and incisional pain. The inflamed tissue by carrageenan was used for the analysis of interleukins (IL), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), c-reactive protein (CRP), nitrite and nitrate (NOx) determination and myeloperoxidase (MPO) activity. Furthermore, we evaluate the possible action mechanism of SBE using naloxone in capsaicin test. RESULTS: SBE prevented the nociception caused by acetic acid, formalin and capsaicin test. However, neither the SBE prevented the thermal hyperalgesia in hot-plate test, nor the naloxone reversed the SBE antinociceptive effect in capsaicin test. Furthermore, the administration of SBE prevented significantly the increase of MPO activity, the NOx content, and the levels of IL-1, IL-6, TNF-α, INF-γ and CRP and was able to increase the IL-10 levels after the inflammation induced by carrageenan in mice. In addition, SBE prevented mechanical hyperalgesia in a postoperative pain model. CONCLUSION: The SBE presents great antinociceptive and anti-inflammatory activity in mice but this effect not seem to have its action mechanism like opioids. It is possible that its antinociceptive effects are associated with levels decrease of inflammatory mediators.

Effects of butane-2,3-dione thiosemicarbazone oxime on testicular damage induced by cadmium in mice.

Our group of studies investigated the action of butane-2,3-dione thiosemicarbazone oxime against the testicular damage caused by cadmium chloride (CdCl(2)) in mice. Mice received a single injection of CdCl(2 )(5 mg/kg, intraperitoneally) and, after thirty minutes, the oxime (10 mg/kg, subcutaneously) was administered. Twenty four hours after the last administration, the animals were killed by cervical dislocation and the testes and serum were removed for analysis. The parameters determined were δ-aminolevulinate dehydratase (δ-ALA-D), myeloperoxidase (MPO), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. The levels of thiobarbituric acid-reactive substances (TBARS), nonprotein thiols (NPSH), ascorbic acid, cadmium and testosterone were also determined. In addition, histological analysis and cytokines quantification (IL-1, IL-6, IL-10, TNF-α and IFN-γ) were performed. Our results demonstrated that the oxime was effective in restoring the inhibition in δ-ALA-D activity induced by CdCl(2). The activation of MPO and increase in IL-1, IL-6, TNF-α and IFN-γ levels induced by CdCl(2) were also reduced by oxime. IL-10, which was reduced by cadmium, was restored by oxime administration. In addition, the oxime was effective in restoring the increase in TBARS levels and the reduction on NPSH levels induced by CdCl(2). Our results demonstrated that oxime was effective in containing the histological alterations induced by CdCl(2). In addition, oxime was able to increase the testosterone levels, reduced by cadmium exposure. In conclusion, the oxime tested was effective in reducing the testicular damage induced by CdCl(2) in mice. The beneficial effects of this oxime are related to its antioxidant and anti-inflammatory action.