Influence of the green tea leaf extract on neurotoxicity of aluminium chloride in rats.

Aluminium may have an important role in the aetiology/pathogenesis/precipitation of Alzheimer's disease. Because green tea (Camellia sinensis L.) reportedly has health-promoting effects in the central nervous system, we evaluated the effects of green tea leaf extract (GTLE) on aluminium chloride (AlCl3 ) neurotoxicity in rats. All solutions were injected into the cornu ammonis region 1 hippocampal region. We measured the performance of active avoidance (AA) tasks, various enzyme activities and total glutathione content (TGC) in the forebrain cortex (FbC), striatum, basal forebrain (BFb), hippocampus, brain stem and cerebellum. AlCl3 markedly reduced AA performance and activities of cytochrome c oxidase (COX) and acetylcholinesterase (AChE) in all regions. It decreased TGC in the FbC, striatum, BFb, hippocampus, brain stem and cerebellum, and increased superoxide dismutase activity in the FbC, cerebellum and BFb. GTLE pretreatment completely reversed the damaging effects of AlCl3 on AA and superoxide dismutase activity, markedly corrected COX and AChE activities, and moderately improved TGC. GTLE alone increased COX and AChE activities in almost all regions. GTLE reduces AlCl3 neurotoxicity probably via antioxidative effects and improves mitochondrial and cholinergic synaptic functions through the actions of (-)-epigallocatechin gallate and (-)-epicatechin, compounds most abundantly found in GTLE. Our results suggest that green tea might be beneficial in Alzheimer's disease.

Beneficial effect of agmatine in the acute phase of experimental autoimmune encephalomyelitis in iNOS-/- knockout mice.

The aim of the study was to investigate the hypothesis that agmatine (AGM) provides protection against oxidative stress in experimental autoimmune encephalomyelitis (EAE). Wild-type (WT) and knockout (KO) CBA/H iNOS-/- 3 months old (15 ± 5 g) mice, were used for EAE induction by myelin basic protein (MBP), dissolved in Complete Freund's Adjuvant (CFA). The animals were divided into control, EAE, CFA, EAE+AGM and AGM groups. After the development of full clinical remission, animals were decapitated and oxidative stress parameters were determined in whole encephalitic mass (WEM) and cerebellum homogenates. The EAE clinical expression manifested to greater extent in WT than KO mice, was significantly decreased during AGM treatment. We demonstrated significant elevations of superoxide dismutase activity in WT and KO EAE animals, in WEM and cerebellum tissues, which were decreased during AGM treatment in both groups. Superoxide anion content was increased in WEM of both study groups, with a decrease during AGM treatment. The observed changes were more pronounced in WT than in KO animals. Also, the increased expressions of transferrin receptor and glial fibrillary acidic protein observed in WT and KO EAE mice were significantly decreased during AGM treatment. The results suggest potentially beneficial AGM effects in EAE, which might be used for a modified antioxidative approach in MS therapy.

Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos.

The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.

Evaluation of Tanacetum larvatum for an anti-inflammatory activity and for the protection against indomethacin-induced ulcerogenesis in rats.

Oral administration of the chloroform extract from Tanacetum larvatum (Griseb. ex Pant.) Kanitz caused a dose-dependent anti-inflammatory effect in the carrageenan-induced rat paw oedema test. The obtained anti-inflammatory effect was 8.6, 32.8, 37.0 and 49.5% for the extract doses of 25, 50, 100 and 200mg/kg, respectively, being statistically significant at a dose of 50mg/kg. Indomethacin had a strong anti-inflammatory effect of 73.4% at a dose of 8mg/kg, but large gastric lesions were detected. When the plant extract in the highest tested dose (200mg/kg) was concomitantly given with indomethacin, the anti-inflammatory effect was slightly enhanced, but the gastric lesions were significantly reduced. The anti-inflammatory and anti-ulcer activity may be mainly due to the inhibition of DNA binding of the transcription factor NF-kappaB by components of the plant extract. This was proven in an electrophoretic mobility shift assay at a concentration of 50microg/ml. Due to its anti-inflammatory as well as anti-ulcer effects, Tanacetum larvatum should especially be used combined with those drugs that are known both for their strong anti-inflammatory activities and the ulcerogenic side effects such as NSAIDs.

Maternal and fetal cadmium and selenium status in normotensive and hypertensive pregnancy.

Cadmium and selenium concentrations in maternal and umbilical cord blood and amniotic fluid were determined in 37 normotensive and 23 hypertensive women during the last trimester of pregnancy in relation to their smoking status. Thiocyanate concentration in plasma was used as the index of smoking status. Cadmium and selenium were determined with atomic absorption spectrometry (graphite furnace and mercury hydride system). In the group of normotensive and hypertensive women, significantly higher cadmium and lower selenium concentrations in blood in smokers were observed than in nonsmokers. Umbilical cord blood selenium concentrations in both normotensive and hypertensive smokers were significantly lower than in nonsmokers as well. In the group of normotensive women, significant differences in selenium concentrations in amniotic fluid were observed between smokers and non-smokers. In conclusion, the results of this study show that hypertension in pregnant women smokers is related to significantly higher blood cadmium concentrations, which indicates that cadmium may be considered as an independent factor involved in hypertension.

Gaba-benzodiazepine receptor complex in brain oxidative metabolism regulation.

This study investigated the impact of modulating the gamma-aminobutyric acid(A) (GABA)(A)-benzodiazepine receptor complex activity on the rat frontal cortex slices oxygen consumption (QO(2)), polarographically determined using the biological oxygen monitor. Throughout the study, diazepam, flumazenil and picrotoxin were administered i.p. 30 min before sacrificing animals and obtaining slice preparations, while GABA was added directly into the medium in the reaction chamber. GABA decreased QO(2) in concentrations of 5 x 10(-4), 10(-2) and 5 x 10(-2)mol l(-1), while 10(-5) and 10(-6)mol l(-1) GABA had no effect, as well as diazepam, flumazenil and picrotoxin. All diazepam doses (1, 2.5 and 5 mg kg(-1)) increased action of 5 x 10(-4)mol l(-1) GABA, whereas 2.5 mg kg(-1) dose amplified the effect of 10(-6)mol l(-1) GABA. Flumazenil and picrotoxin (5 mg kg(-1) both) blocked diazepam's effects. Flumazenil augmented 10(-6)mol l(-1) GABA effects, while picrotoxin and flumazenil abolished the effects of 5 x 10(-4)mol l(-1) GABA. To our knowledge, this is the first study to examine the influence of modulation of GABA(A)-benzodiazepine receptor function on cerebral metabolism of oxygen in in vitro settings. The results are in accordance with those obtained in numerous in vivo studies, pointing to the moderate level of influence of GABA(A)-benzodiazepine receptor complex on QO(2) regulation.