Effect of Hypericum perforatum on different models of movement disorders in rats.

The effects of Hypericum perforatum, a plant with antidepressant action, were evaluated in models of abnormal movements in rats, brought about by administration of fluphenazine or reserpine. The number of vacuous chewing movements (VCMs) and locomotor activity (the number of crossings and rears in the open field test) were measured. In experiment 1, rats received a single administration of fluphenazine enanthate (25 mg/kg, intramuscular) and/or daily treatment with H. perforatum (300 mg/kg, in place of drinking water) for 7 days. Fluphenazine increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the locomotor activity. In experiment 2, rats received reserpine every 2 days for 6 days (0.5 mg/kg, subcutaneous) and/or H. perforatum (300 mg/kg, in place of drinking water) daily for 16 days beginning 10 days before the first administration of reserpine. Reserpine treatment increased VCMs and decreased locomotor activity. H. perforatum had no effect on either the number of VCMs or the number of rears but did prevent the effect of reserpine on the number of crossings. In conclusion, H. perforatum failed to protect against orofacial movements induced by fluphenazine or reserpine in rats.

Aqueous extract of pecan nut shell (Carya illinoensis [Wangenh.] K. Koch) exerts protection against oxidative damage induced by cyclophosphamide in rat testis.

This study investigated the protective effect of pecan nut (Carya illinoensis) shell aqueous extract (AE) on the oxidative and morphological status of rat testis treated with cyclophosphamide (CP). Wistar rats received water or AE (5%) ad libitum for 37 days. On day 30, half of each group received a single intraperitoneal administration of vehicle or CP 200 mg/kg. After 7 days, the animals were killed and their testis removed. Rats treated with CP presented reduced levels of lactate dehydrogenase, vitamin C, and gluthatione, as well as decreased catalase activity, increased lipid peroxidation levels and superoxide dismutase activity, no alteration in carbonyl protein levels, and a loss of morphological testicular integrity. In contrast, cotreatment with pecan shell AE totally prevented the decrease of lactate dehydrogenase and vitamin C levels and catalase activity and partially prevented the depletion of gluthatione levels. Moreover, it totally prevented the increase in superoxide dismutase activity and lipid peroxidation levels and maintained testicular integrity. These findings show the protective role of pecan shell AE in CP-induced testicular toxicity. The use of this phytotherapy may be considered to minimize deleterious effects related to this chemotherapy.

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.

Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment.

We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.

Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract.

Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal.

Short term dietary fish oil supplementation improves motor deficiencies related to reserpine-induced parkinsonism in rats.

Fish oil (FO) supplementation could cause an increase in the concentration of plasmatic free fatty acids and, consequently, could compete with pro-inflammatory arachidonic acid (ARA) derived from brain biomembranes metabolism in the cerebrospinal fluid. Essential fatty acids (EFA) (n-3) have been reported by their antioxidant and neuroprotective properties, and therefore the influence of the FO supplementation on the reserpine-induced motor disorders was studied. Wistar rats were orally treated with FO solution for 5 days, and co-treated with reserpine (R; 1 mg/kg/mL) or its vehicle for 3 days (every other day). Reserpine-induced orofacial dyskinesia and catalepsy (P < 0.05) were prevented by FO (P < 0.05). Biochemical evaluations showed that reserpine treatment increased the lipid peroxidation in the cortex and striatum (P < 0.05), while the FO supplementation prevented this oxidative effect in both brain regions (P < 0.05). Our results showed the protective role of FO in the brain lipid membranes, reinforcing the beneficial effect of n-3 fatty acids in the prevention of degenerative and motor disorders.

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.

Effects of omega-3 essential fatty acids (omega-3 EFAs) on motor disorders and memory dysfunction typical neuroleptic-induced: behavioral and biochemical parameter.

The effects of fish oil supplementation on motor disorders, memory dysfunction, and lipid peroxidation (LP) induced by typical neuroleptics were studied. Wistar rats received a suspension prepared with fish oil containing omega-3 fatty acids, water, and Tween 80 (1%) in the place of drinking water (FO group) or vehicle (C group) for 8 weeks. After 4 weeks of treatment, half of the animals of both groups were treated with haloperidol (H and FO + H groups; experiment 1), fluphenazine (F and FO + F groups; experiment 2), or vehicle (C group), administered once a week (12 mg/kg/im) for 4 weeks, maintaining the treatment with FO. Extrapyramidal motor disorders by haloperidol and fluphenazine were observed by an increase in vacuous chewing movements and catalepsy (P < 0.05). These effects were reduced by FO treatment (P < 0.05). Both neuroleptics displayed impairment in memory retention observed by latency time to find the original location of platform in water-maze task, after 4 days of training performed in the last treatment week. This effect was reduced by FO (P < 0.05) to both haloperidol and fluphenazine treatments. Haloperidol increased the LP in plasma and hippocampus, and these effects were decreased by FO treatment (P < 0.05). Fluphenazine increased the LP in plasma and substantia nigra, which were completely decreased by FO treatment (P < 0.05). The FO decreased the motor disorders, memory dysfunction, and oxidative damage typical neuroleptic-induced. Our results indicate that FO exhibits a neuroprotector role useful on diseases related to oxidative damages, and may be considered in the prevention of motor and memory side effects induced by the antipsychotic treatment.