Angélica M. Teixeira

Influence of chronic exercise on reserpine-induced oxidative stress in rats: Behavioral and antioxidant evaluations

Several neurological diseases are related to oxidative stress (OS) and neurotoxicity. Considering that physical exercise may exert beneficial effects on antioxidant defenses, our objective was to evaluate the influence of a swimming exercise on an OS animal model (reserpine-induced orofacial dyskinesia). In this model, the increased dopamine metabolism can generate OS and neuronal degeneration, causing involuntary movements. The increase in vacuous chewing movements and facial twitching caused by reserpine (1 mg/kg s.c.) was partially prevented by exercise. An increase in catalase activity and a decrease in GSH levels were observed in the striatum. Physical training did not change the effects of reserpine on catalase, however it partially recovered GSH. Exercise per se caused a significant GSH decrease. There was a positive correlation between catalase and OD (r=0.41; r=0.47, P<0.05) and a negative correlation between GSH and OD (r=0.61; r=0.71, P<0.05). These results reveal the benefit of exercise in attenuating the motor disorder related to OS.

Exercise affects memory acquisition, anxiety-like symptoms and activity of membrane-bound enzyme in brain of rats fed with different dietary fats: impairments of trans fat

Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.

Could dietary trans fatty acids induce movement disorders? Effects of exercise and its influence on Na⁺K⁺-ATPase and catalase activity in rat striatum.

The influence of trans fatty acids (FA) on development of orofacial dyskinesia (OD) and locomotor activity was evaluated. Rats were fed with diets enriched with 20% soybean oil (SO; n-6 FA), lard (L; saturated FA) or hydrogenated vegetable fat (HVF; trans FA) for 60 weeks. In the last 12 weeks each group was subdivided into sedentary and exercised (swimming). Brains of HVF and L-fed rats incorporated 0.33% and 0.20% of trans FA, respectively, while SO-fed group showed no incorporation of trans FA. HVF increased OD, while exercise exacerbated this in L and HVF-fed rats. HVF and L reduced locomotor activity, and exercise did not modify. Striatal catalase activity was reduced by L and HVF, but exercise increased its activity in the HVF-fed group. Na(+)K(+)-ATPase activity was not modified by dietary FA, however it was increased by exercise in striatum of SO and L-fed rats. We hypothesized that movement disorders elicited by HVF and less by L could be related to increased dopamine levels in striatum, which have been related to chronic trans FA intake. Exercise increased OD possibly by increase of brain dopamine levels, which generates pro-oxidant metabolites. Thus, a long-term intake of trans FA caused a small but significant brain incorporation of trans FA, which favored development of movement disorders. Exercise worsened behavioral outcomes of HVF and L-fed rats and increased Na(+)K(+)-ATPase activity of L and SO-fed rats, indicating its benefits. HVF blunted beneficial effects of exercise, indicating a critical role of trans FA in brain neurochemistry.

Ilex paraguariensis has antioxidant potential and attenuates haloperidol-induced orofacial dyskinesia and memory dysfunction in rats.

Tardive dyskinesia (TD) is a syndrome associated with administration of antipsychotics drugs and may be a consequence of a free radical increase.Ilex paraguariensis (IP), rich in polyphenols, is used to prepare a tea-like beverage, the “mate”, and has been investigated for its antioxidant action. Here, we examined the aqueous extract ofIP onin vitro TBARS production andin vivo study, using two behavioral models,i.e., haloperidol-induced orofacial dyskinesia (evaluated measuring vacuous chewing movements, VCMs) and memory dysfunction, evaluated in a watermaze task. Invitro, we examine different concentrations ofIP against the basal, Fe(II) and sodium nitruproside-induced TBARS production in rat brain homogenate.IP extract was able to prevent the basal formation of TBARS (IC50=6.6 mg/ml) and TBARS induced by SNP (IC50=3.7 mg/ml) and Fe(II) (IC50=4.8 mg/ml). Haloperidol administration (12 mg/kg/week, im, x4 weeks) increased VCMs (p<0.001). Rats treated with mate (50 g/l,ad libitum, 60 days) did not exhibit the increase in VCMs observed in control rats treated with haloperidol (p<0.001). In the water maze task, haloperidol treated animals displayed an impairment in memory acquisition (p<0.05) compared to rats treated with vehicle. The “mate” prevented the effects of haloperidol in this behavioral paradigm. Our results indicate thatIP exhibits an antioxidant role probably related to the presence of polyphenols. The benefit ofIP is possibly related to an indirect modulation of oxidative stress.

Intense exercise potentiates oxidative stress in striatum of reserpine-treated animals.

Regular physical activity exerts beneficial effects for mental and physical health, but an intense exercise can cause oxidative stress (OS) in dopaminergic regions and intensify the harmful effects of reserpine. Reserpine-induced neurotoxicity can be accessed by behavioral and biochemical evaluations. The objective of this study was to examine the effect of a gradual intensifying exercise program on an animal model of oxidative stress. Male rats were submitted to swimming sessions (1 h/day, for eleven weeks), and they were loaded gradually during the adaptation period (two weeks) with a weight corresponding to 1-7% of their body weight tied to their back. After the last training, the animals were treated with two doses of vehicle or reserpine (1 mg/kg-sc), an agent that induces orofacial dyskinesia. After behavioral evaluations, the striatum was dissected for enzymatic and biochemical assays. Development of cardiac hypertrophy demonstrated the effectiveness of the physical training. The gradual intense exercise and reserpine increased lipid peroxidation and striatal catalase activity. The results confirm the importance of catalase activity in orofacial dyskinesia which can be related to lipid peroxidation in striatal dopaminergic brain tissue. These results indicate that intense exercise can have some deleterious effect on striatal dopaminergic system.

Comparative study between n-6, trans and n-3 fatty acids on repeated amphetamine exposure: a possible factor for the development of mania.

In the last decades, foods rich in omega-3 (ω-3) fatty acids (FA) have been replaced by omega-6 (ω-6) and trans FA, which are found in processed foods. The influence of ω-6 (soybean oil--SO), trans (hydrogenated vegetable fat--HVF) and ω-3 (fish oil--FO) fatty acids on locomotor and oxidative stress (OS) parameters were studied in an animal model of mania. Rats orally fed with SO, HVF and FO for 8 weeks received daily injections of amphetamine (AMPH--4 mg/kg/mL-ip) for the last week of oral supplementation. HVF induced hyperactivity, increased the protein carbonyl levels in the cortex and decreased the mitochondrial viability in cortex and striatum. AMPH-treatment increased the locomotion and decreased the mitochondrial viability in all groups, but its neurotoxicity was higher in the HVF group. Similarly, AMPH administration increased the protein carbonyl levels in striatum and cortex of HVF-supplemented rats. AMPH reduced the vitamin-C plasmatic levels of SO and HVF-fed rats, whereas no change was observed in the FO group. Our findings suggest that trans fatty acids increased the oxidative damage per se and exacerbated the AMPH-induced effects. The impact of trans fatty acids consumption on neuronal diseases and its consequences in brain functions must be further evaluated.

Oxidative stress and anxiety-like symptoms related to withdrawal of passive cigarette smoke in mice: Beneficial effects of pecan nut shells extract, a by-product of the nut industry

The present study evaluated the role of pecan nut (Carya illinoensis) shells aqueous extract (AE) against oxidative damage induced by cigarette smoke exposure (CSE) and behavioral parameters of smoking withdrawal. Mice were passively exposed to cigarette smoke for 3 weeks (6, 10, and 14 cigarettes/day) and orally treated with AE (25 g/L). CSE induced lipid peroxidation in brain and red blood cells (RBC), increased catalase (CAT) activity in RBC, and decreased plasma ascorbic acid levels. AE prevented oxidative damage and increased antioxidant defenses of mice exposed to cigarette smoke. In addition, AE reduced the locomotor activity and anxiety symptoms induced by smoking withdrawal, and these behavioral parameters showed a positive correlation with RBC lipid peroxidation. Our results showed the beneficial effects of this by-product of the pecan industry, indicating its usefulness in smoking cessation.

Beneficial effects of an innovative exercise model on motor and oxidative disorders induced by haloperidol in rats.

Here we evaluate the influence of a new exercise protocol on movement disorders induced by neuroleptic drugs. In this animal model, involuntary movements are closely related to neuronal degeneration and oxidative stress (OS) that can be caused by pre-synaptic D2 receptor blockade increasing dopamine (DA) metabolism. The increase in vacuous chewing movements (VCM) and the reduced locomotor activity induced by haloperidol treatment (12 mg/kg-im, once a week for 4 weeks) was prevented by exercise, 5 times per week, which was initiated four weeks before the first haloperidol administration. Exercise training also prevented the increase of haloperidol-induced lipid peroxidation in the cortex and subcortical region and recovered the catalase activity in the subcortical region. There was a negative correlation between catalase activity in the subcortical region and the VCM frequency (r = 0.50, p < 0.05), as well as a positive correlation between VCM frequency and lipid peroxidation in the cortex (r = 0.64, p < 0.05) and subcortical region (r = 0.71, p < 0.0001). Both haloperidol and exercise increased DA uptake in the striatum, while the co-treatment (exercise plus haloperidol) reduced it. The striatal DA uptake correlated negatively with catalase activity (r = 0.51, p < 0.05), indicating a relationship between oxidative damage and the function of the transporter in the striatum. Our findings show that physical exercise can modulate dopamine uptake, especially when it is altered, and reveal the benefit of this new exercise protocol in the prevention of movement disorders related to oxidative damage.

Beneficial effects of gradual intense exercise in tissues of rats fed with a diet deficient in vitamins and minerals: A pilot study

OBJECTIVE This study evaluated the preliminary effects of intense physical training (swimming) on oxidative stress in rats with nutritional deficiencies. METHODS Rats were fed with a standard diet or a diet deficient in vitamins and minerals for 4 months. The deficient diet contained one-fourth of the recommended vitamin and mineral levels for rats. From the second month, half of the animals were subjected to a swimming exercise in a plastic container with water maintained at 34 +/- 1 degrees C for 1 h/d, five times per week, for 11 wk. The rats were subjected to swimming exercise with loads attached to the dorsal region, which were progressively increased according to their body weight (1% to 7%). Sedentary rats were transported to the experimental room and handled as often in a similar way as the exercise group, except that they were not put in water. RESULTS In the exercised group, blood lactate levels were significantly lower and the heart weight/body weight ratio was significantly higher than in the sedentary group (P < 0.05). Increased lipid peroxidation was observed in the liver, heart, and skeletal muscle of rats fed with the deficient diet, but it was completely reversed by exercise. Exercise also decreased lipid peroxidation levels in the heart and skeletal muscle of rats fed with the standard diet (P < 0.05). CONCLUSION This pilot study leads to the continuity of the studies, because the partial results observed suggest that inadequate nutrition may enhance oxidative stress, and that intense chronic physical training may activate antioxidant defenses, possibly by hormesis.

Prolonged consumption of trans fat favors the development of orofacial dyskinesia and anxiety-like symptoms in older rats

Abstract Polyunsaturated fatty acids (FAs) are cell membrane components involved in brain functions. We hypothesized that long-term trans fat consumption is able to modify the membrane FAs composition impairing behavioral parameters related to aging. In this study, a comparison of behavioral parameters at 10 and 15 months of trans fat consumption by male Wistar rats was made. Animals were fed for 10 and 15 months from weaning with diets containing either 20% w/w soybean oil (SO), rich in n-6 PUFA, hydrogenated vegetable fat (HVF), rich in trans FAs, or a standard diet (control – C). At both evaluation times, HVF-fed rats showed progressively increased parameters of orofacial dyskinesia, fear and anxiety-like symptoms. The HVF diet reduced locomotor and exploratory activities progressively over 10 and 15 months of supplementation, while the standard and SO diets did not. In this study, we showed that chronic trans FAs consumption from weaning is able to favor the development of neuromotor and neuropsychiatric diseases, whose intensity was time dependent.