Marta Maria de França Fonteles

Oxidative stress in the hippocampus after pilocarpine‐induced status epilepticus in Wistar rats

The role of oxidative stress in pilocarpine‐induced status epilepticus was investigated by measuring lipid peroxidation level, nitrite content, GSH concentration, and superoxide dismutase and catalase activities in the hippocampus of Wistar rats. The control group was subcutaneously injected with 0.9% saline. The experimental group received pilocarpine (400 mg·kg−1, subcutaneous). Both groups were killed 24 h after treatment. After the induction of status epilepticus, there were significant increases (77% and 51%, respectively) in lipid peroxidation and nitrite concentration, but a 55% decrease in GSH content. Catalase activity was augmented 88%, but superoxide dismutase activity remained unaltered. These results show evidence of neuronal damage in the hippocampus due to a decrease in GSH concentration and an increase in lipid peroxidation and nitrite content. GSH and catalase activity are involved in mechanisms responsible for eliminating oxygen free radicals during the establishment of status epilepticus in the hippocampus. In contrast, no correlations between superoxide dismutase and catalase activities were observed. Our results suggest that GSH and catalase activity play an antioxidant role in the hippocampus during status epilepticus.

Oxidative stress and epilepsy: literature review.

Backgrounds. The production of free radicals has a role in the regulation of biological function, cellular damage, and the pathogenesis of central nervous system conditions. Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy. Objective. A review was conducted to investigate the link between oxidative stress and seizures, and oxidative stress and age as risk factors for epilepsy. The role of oxidative stress in seizure induction and propagation is also discussed. Results/Conclusions. Oxidative stress and mitochondrial dysfunction are involved in neuronal death and seizures. There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models. Studies have demonstrated that mitochondrial dysfunction is associated with chronic oxidative stress and may have an essential role in the epileptogenesis process; however, few studies have shown an established link between oxidative stress, seizures, and age.

Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission.

Carvacrol (5‐isopropyl‐2‐methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate‐induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open‐field test. However, CVC decreased the number of groomings in the open‐field test. In the plus maze test, CVC, at three doses significantly increased all the observed parameters in the EPM test and flumazenil was able to reverse the effects of diazepam and CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate‐induced sleeping time test. These results show that CVC presents anxiolytic effects in the plus maze test which are not influenced by the locomotor activity in the open‐field test.

Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice.

A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug.

Pilocarpine-induced status epilepticus in rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex.

The aim of the study was to investigate the lipid peroxidation levels, nitrite formation, GABAergic and glutamatergic receptor densities in the hippocampus, frontal cortex and striatum of Wistar rats after seizures and status epilepticus (SE) induced by pilocarpine. The control group was treated with 0.9% saline and sacrificed 1 h after the treatment. One group of rats was administered with pilocarpine (400 mg/kg sc) and sacrificed 1 h after treatment. The result shows that pilocarpine administration and the resulting SE produced a significant increase of lipid peroxidation level in the hippocampus (46%), striatum (25%) and frontal cortex (21%). In nitrite formation, increases of 49%, 49% and 75% in hippocampus, striatum and frontal cortex, respectively, was observed. Pilocarpine treatment induced down-regulation of GABAergic receptors in the hippocampus (38%), striatum (15%) and frontal cortex (11%). However, with regard to glutamatergic receptor densities, increases in the hippocampus (11%), striatum (17%) and frontal cortex (14%) was observed during the observation period. These results show a direct evidence of lipid peroxidation and nitrite formation during seizure activity that could be responsible for the GABAergic and glutamatergic receptor concentration changes during the establishment of SE induced by pilocarpine.

Attenuating effects of melatonin on pilocarpine-induced seizures in rats.

Daily melatonin (10-50 mg/kg, i.p.) treatment at 08.30 h or 17.00 h for 1 week of female rats (2-months-old) increased the latency to the appearance of the first convulsion in the pilocarpine-induced seizure model. Other behavior parameters remained unaltered. The anticonvulsant effect of melatonin seemed to be more intense at the light-dark transition. Moreover, the effect of repeated melatonin treatment was also age-related, since it showed a lower threshold in 2-month-old than in 21-day-old rats, and the acute treatment was not efficient. [3H]N-methylscopolamine binding was unaltered in the hippocampus and striatum of adult rats after the association of melatonin and pilocarpine. While muscarinic binding was unaltered in adult rats, it increased in the hippocampus of young rats in the presence of melatonin (50 mg/kg) and pilocarpine, and did not change in the striatum. Melatonin partially recovered [3H]GABA binding in the hippocampus in the presence of pilocarpine-induced seizures, and intensified pilocarpine effects in the striatum of adult rats.

Catalase activity in cerebellum, hippocampus, frontal cortex and striatum after status epilepticus induced by pilocarpine in Wistar rats.

The mechanism underlying the vulnerability of the brain to status epilepticus (SE) induced by pilocarpine remains unknown. Oxidative stress has been implicated in a variety of acute and chronic neurologic conditions, including SE. The present study was aimed at was investigating the changes in catalase activity after pilocarpine-induced seizures and SE. The Control group was treated with 0.9% saline (NaCl, subcutaneously (s.c.)) and sacrificed 1h after the treatment. Another group was treated with pilocarpine (400 mg/kg, s.c., Pilocarpine group) and sacrificed 1h after treatment. The catalase activity in the cerebellum, hippocampus, frontal cortex and striatum of Wistar rats was determined. The results have shown that pilocarpine administration and resulting SE produced a significant increase in the catalase activity in the hippocampus (36%), striatum (31%) and frontal cortex (15%) of treated adult rats. Nevertheless, in the adult rat cerebellum after SE induced by pilocarpine no change was observed in the catalase activity. Our results demonstrated a direct evidence of an increase in the activity of the scavenging enzyme (catalase) in different cerebral structures during seizure activity that could be responsible for eliminating oxygen free radicals and might be one of the compensatory mechanisms to avoid the development of oxidative stress during the establishment of SE induced by pilocarpine. Our reports also indicate clear regional differences in the catalase activity caused by pilocarpine-induced seizures and SE and the hippocampus might be the principal area affected and cerebellum does not modify for this parameter studied during epileptic activity.

Plantas medicinais e seus constituintes bioativos: uma revisão da bioatividade e potenciais benefícios nos distúrbios da ansiedade em modelos animais

A procura de novos agentes terapeuticos provenientes de plantas medicinais para doencas psiquiatricas tem progredido significativamente na ultima decada. Isso reflete num grande numero de preparacoes herbarias para as quais o potencial psicoterapeutico tem sido avaliado em diversos modelos animais. O intuito desta revisao e fornecer uma ampla visao das plantas medicinais que apresentam efeitos terapeuticos significantes em modelos animais de doencas psiquiatricas, especificamente os disturbios da ansiedade. Um consideravel numero de constituintes herbarios cujos efeitos comportamentais e acoes farmacologicas tem sido bem caracterizados podem ser bons candidatos para futuras investigacoes que podem resultar em uso clinico, merecendo, portanto, uma maior atencao em estudos posteriores.

Antianxiety and antidepressant effects of riparin III from Aniba riparia (Nees) Mez (Lauraceae) in mice

This work presents behavioral effects of methyl ethers of N-(2,6-dihydroxybenzoyl) tyramine (riparin III) isolated from the unripe fruit of Aniba riparia on the open field, elevated plus maze (EPM), rotarod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Riparin III was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg. The results showed that riparin III with both doses had no effects on spontaneous motor activity in mice or in the rotarod test, but decreased the number of grooming and rearing. At the dose of 50 mg/kg, riparin III increased the number of entries in the open arms of the EPM test as compared with control. Similarly, in the hole-board test, both doses increased the number of head dips. There was a reduction on the sleeping latency with both doses and a prolongation of the pentobarbital-induced sleeping time with the dose of 25 mg/kg. In the tail suspension test, similar to imipramine (30 mg/kg), riparin III at the dose of 50 mg/kg presented a reduction in the immobility time. In the forced swimming test, both doses of riparin III decreased the immobility time. These results showed that riparin III potentiated the barbiturate-induced sleeping time and presented antidepressant- and anxiolytic-like effects.

Antidepressant-like effect of carvacrol (5-Isopropyl-2-methylphenol) in mice: involvement of dopaminergic system

Carvacrol (5‐isopropyl‐2‐methylphenol) is a monoterpenic phenol present in the essential oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. In this study, the effect of carvacrol was investigated in two behavioral models, the forced swimming and tail suspension tests in mice, to investigate the possible antidepressant effect of this substance. Additionally, the mechanisms involved in the antidepressant‐like effect of carvacrol in mice were also assessed. Carvacrol (cvc) was administered orally at single doses of 12.5, 25 and 50 mg/kg. The acute treatment of cvc decreased the immobility time in the forced swimming and tail suspension tests without accompanying changes in ambulation in the open‐field test. The anti‐immobility effect of carvacrol (25 mg/kg) was not prevented by pretreatment of mice with p‐chlorophenylalanine, prazosin and yohimbine. On the other hand, the pretreatment of mice with SCH23390 or sulpiride completely blocked the antidepressant‐like effect of carvacrol (25 mg/kg) in the forced swimming test. These results show that carvacrol presents antidepressant effects in the forced swimming and tail suspension tests; this effect seems to be dependent on its interaction with the dopaminergic system, but not with the serotonergic and noradrenergic systems. Keywords: Carvacrol; Antidepressant; Forced swimming; Tail suspension; Dopaminergic system.