Chistiane Mendes Feitosa

Antioxidant and antinociceptive effects of Citrus limon essential oil in mice.

The antioxidant and antinociceptive activities of Citrus limon essential oil (EO) were assessed in mice or in vitro tests. EO possesses a strong antioxidant potential according to the scavenging assays. Moreover, it presented scavenger activity against all in vitro tests. Orally, EO (50, 100, and 150 mg/kg) significantly reduced the number of writhes, and, at highest doses, it reduced the number of paw licks. Whereas naloxone antagonized the antinociceptive action of EO (highest doses), this suggested, at least, the participation of the opioid system. Further studies currently in progress will enable us to understand the action mechanisms of EO.

Antioxidant activity of Citrus limon essential oil in mouse hippocampus

Context: Citrus limon (L.) Burms (Rutaceae) has been shown in previous studies to have various biological functions (anti-inflammatory, antiallergic, antiviral, antimutagenic, and anticarcinogenic). However, traditional uses in folk medicine suggest that C. limon may have an effect on the central nervous system (CNS). Objective: This study investigated the effects of C. limon essential oil (EO) on lipid peroxidation level, nitrite content, glutathione reduced (GSH) concentration, and antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx)] activities in mice hippocampus. Materials and methods: Swiss mice were treated with the suspension of 0.5% Tween 80, in distilled water used as vehicle (i.p., control group) and with EO in three different doses (0.05, 0.1, or 0.15 g/kg, i.p., EO 50, EO 100, and EO 150 groups, respectively). After the treatments, all groups were observed for 24 h. The enzyme activities as well as the lipid peroxidation, nitrite, and GSH concentrations in mice hippocampus were measured using spectrophotometric methods and the results were compared with values obtained from control group. Results: EO of C. limon treatment significantly reduced the lipid peroxidation level and nitrite content but increased the GSH levels and the SOD, catalase, and GPx activities in mice hippocampus. Discussion and conclusion: Our findings strongly support the hypothesis that oxidative stress in hippocampus can occur during neurodegenerative diseases, proving that hippocampal damage induced by the oxidative process plays a crucial role in brain disorders, and also imply that a strong protective effect could be achieved using EO of C. limon as an antioxidant.

Atividades larvicida e anticolinesterásica de plantas do gênero Kalanchoe

Acetylcholine esterase inhibitors are successfully used to treat the symptoms of Alzheimers disease. Extracts of three Kalanchoe species (K. brasiliensis, K. pinnata and K. gastonis-bornieri) showed acetylcholine esterase inhibitory effects and a toxic effect on Aedes aegypti larvae. Here we describe the bioassay guided fractionation of extracts of the most active extracts (K. brasiliensis) which resulted in the isolation of an active mixture of three flavonoids: 8-methoxyquercetin, 3,7-di-O-rhamnopyranoside and 8-methoxykaempferol-3,7-di-O-rhamnopyranoside. On TLC these flavonoids showed an acetylcholine esterase inhibitory effect.

Lipoic acid blocks seizures induced by pilocarpine via increases in δ-aminolevulinic dehydratase and Na+, K+-ATPase activity in rat brain

In the present study we investigated the effects of lipoic acid (LA) on delta-aminolevulinic dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities in rat brain after seizures induction by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (10mg/kg, i.p., LA group), pilocarpine (400mg/kg, i.p., pilocarpine group), or the combination of LA (10mg/kg, i.p.) with pilocarpine (400mg/kg, i.p.), 30 min before administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 1h. The enzyme activities (delta-ALA-D and Na(+), K(+)-ATPase) were measured using spectrophotometric methods, and the results were compared with that obtained from saline and pilocarpine-treated animals. Neuroprotective effects of LA against seizures were evaluated based on those enzyme activities. The pilocarpine group showed a reduction in delta-ALA-D and Na(+), K(+)-ATPase activities after seizures. In turn, LA plus pilocarpine abolished the appearance of seizures and reversed the decreased in delta-ALA-D and Na(+), K(+)-ATPase activities produced by seizures, when compared to the pilocarpine seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing delta-ALA-D and Na(+), K(+)-ATPase activities in rat brain during seizures.

Neuronal damage and memory deficits after seizures are reversed by ascorbic acid

The objective of the present study was to evaluate the neuroprotective effects of ascorbic acid (AA) in rats, against the neuronal damage and memory deficit caused by seizures. Wistar rats were treated with 0.9% saline (i.p., control group), ascorbic acid (500 mg/kg, i.p., AA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of ascorbic acid (500 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of ascorbic acid (AA plus pilocarpine group). After the treatments all groups were observed for 24 h. Pilocarpine group presented seizures which progressed to status epilepticus in 75% of the animals. Pretreatment with AA led to a reduction of 50% of this rate. Results showed that pretreatment with AA did not alter reference memory when compared to a control group. In the working memory task, we observed a significant days effect with important differences between control, pilocarpine and AA plus pilocarpine groups. Pilocarpine and AA plus pilocarpine groups had 81 and 16% of animals with brain injury, respectively. In the hippocampus of pilocarpine animals, it was detected an injury of 60%. As for the animals tested with AA plus pilocarpine, the hippocampal region of the group had a reduction of 43% in hippocampal lesion. Our findings suggest that seizures caused cognitive dysfunction and neuronal damage that might be related, at least in part, to the neurological problems presented by epileptic patients. AA can reverse cognitive dysfunction observed in rats with seizures as well as decrease neuronal injury in rat hippocampus.

Lipoic acid inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after pilocarpine-induced seizures.

Alpha-lipoic acid has some neuroprotective properties, but this action has not been investigated in models of epilepsy. The aim of the present study was to investigate the protective efficacy of α-lipoic acid (lipoic acid) against pilocarpine-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Wistar rats were injected intraperitoneally with 0.9% saline (control group), pilocarpine (400 mg/kg, pilocarpine group) alone, or α-lipoic acid (20 mg/kg) in association with pilocarpine (400 mg/kg) 30 min before administration of α-lipoic acid. After the treatments all groups were observed for 24 h. Cell death was reduced in lipoic acid-treated rats. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were reduced by lipoic acid treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also decreased in lipoic acid-treated rats. Our study suggests that lipoic acid inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage during pilocarpine-induced seizures.

Investigation of biological activities of dichloromethane and ethyl acetate fractions of Platonia insignis Mart. seed.

Platonia insignis Mart., a native species of the Brazilian Amazon more commonly known as bacuri, is a member of the Clusiaceae family. In this study, we evaluated the chemical composition and the antioxidant and toxicity activities of the dichloromethane and ethyl acetate fractions from P. insignis seed ethanolic extract using different experimental models. Our results demonstrate in vitro antioxidant effects, by 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) diammonium salt and 1,1‐diphenyl‐2‐picryl‐hydrazyl assays, as well as in vivo effects in antioxidant‐defective Saccharomyces cerevisiae strains to both fractions. Toxicity was evaluated against the micro‐crustaceous Artemia salina Leach. and promastigote Leishmania amazonensis. The dichloromethane fraction was the most active fraction evaluated on A. salina and promastigote L. amazonensis (IC50 = 24.89 μg/mL and 2.84 μg/mL, respectively). In addition, a slight cytotoxicity was observed in mammalian V79 cells using ethyl acetate and dichloromethane fractions with MTT assays. Both fractions displayed genotoxicity up to 25 μg/mL (dichloromethane) and 10 μg/mL (ethyl acetate) in V79 cells, as evaluated by the alkaline comet assay. Thus, in this study, we demonstrate for the first time that ethyl acetate and dichloromethane fractions from P. insignis seeds display antioxidant effects, a toxic effect against A. salina and L. amazonensis and induce genotoxicity in V79 mammalian cells. The observed activities can be attributed to the phenolic compounds present in these fractions and to the presence of xanthones (alpha‐ and gamma‐mangostin).

Evaluation of central nervous system effects of Citrus limon essential oil in mice

The central nervous system (CNS) depressant and anticonvulsant activities of Citrus limon (L.) Osbeck, Rutaceae, essential oil (EO) were investigated in animal models. The EO (50, 100 and 150 mg/kg) injected by oral route (p.o.) in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to thirty days after the administration and the dose of 150 mg/kg significantly reduced the remaining time of the animals on the Rota-rod apparatus. Additionally, C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). The administration of FLU (10 mg/kg, i.p.), GABAA-benzodiazepine (GABA-BZD) receptor antagonist, antagonized the effect of C. limon essential oil at higher dose. This C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at higher dose. In the same way, the anticonvulsant effect of the EO was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABAA receptor. These results suggest a possible CNS depressant and anticonvulsant activities in mice that needs further investigation.

Effects of ubiquinone on hydroperoxide concentration and antioxidant enzymatic activities in the rat hippocampus during pilocarpine-induced seizures.

Recent researches have shown that antioxidant compounds may have certain neuroprotective effect against the neurotoxicity of seizures at cellular level. Ubiquinone (UQ), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. The objective of the present study was to evaluate the neuroprotective effects of UQ in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with either 0.9% saline (i.p., control group), UQ (5, 10 or 20 mg/kg, i.p., UQ5, UQ10 and UQ20 groups), pilocarpine (400 mg/kg, i.p., P400 group), or co-administration of pilocarpine with UQ group rats 30 min prior to UQ administration. After the treatments all groups were observed for 24 h. The antioxidant enzymatic activities as well as the hydroperoxide concentrations were measured using spectrophotometric methods and the results were analyzed. In pilocarpine group there was a significant increase in hydroperoxides concentration and glutathione peroxidase activity. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the hydroperoxide content and increased the superoxide dismutase, catalase and glutathione peroxidase activities in rat hippocampus during seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, which indicates that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences. Our result also suggests that ubiquinone can exert significant neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.

Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.