Melatonin promotes orofacial antinociception in adult zebrafish by modulating TRP channels.

Melatonin is an endogenous hormone, known as the sleep hormone, which has already demonstrated its antinociceptive effect. This study aimed to evaluate the participation of TRP's channels in the orofacial antinociceptive effect of melatonin (MT) in adult zebrafish. Initially, the open field test was performed to evaluate the effect of MT on the locomotor activity of adult zebrafish. Then, the animals were pre-treated with MT (0.1, 0.3 or 1 mg/mL; gavage) and acute orofacial nociception was induced by the application of capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist) or menthol (TRPM8 agonist) applied into the animal's lip. Naive groups were included. MT, per se, did not alter the locomotor activity of the animals. MT reduced the nociceptive behavior induced by the three agonists; however, the most significant effect was obtained with the lowest concentration tested (0.1 mg/mL) in the capsaicin test. The orofacial antinociceptive effect of melatonin was prevented by capsazepine (TRPV1 antagonist), but not by HC-030031 (TRPA1 antagonist). The molecular docking study indicated interaction between MT and the TRPV1, TRPA1 and TRPM8 channels and, in line with the in vivo results, there was greater affinity between MT and the TRPV1 channel. The results confirm the pharmacological relevance of melatonin as an inhibitor of orofacial nociception and this effect seems to be related to the modulation of TRP's channels.

Pharmacological Potential of cis-jasmone in Adult Zebrafish (Danio rerio).

This study evaluates the pharmacological potential of cis-jasmone (CJ) in adult zebrafish (Danio rerio; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; p. o.) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABAA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABAA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.

Audiovisual overstimulation in childhood and adolescence promotes hyperactive behaviour in adult mice.

There is a discussion about the impact of technological development on behavioural aspects, a nuance that the present study aimed to assess. p21, p26 and p36 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for 2 or 6 h per day until p64. Naive animals were included. From p74 onwards, the animals were subjected to tests to assess their locomotion, depression, anxiety, aggressiveness, and nociception behaviours. Weight assessment was also performed. The animals that received stimulation for 2 h a day since p21 showed a decrease in rearing and grooming behaviour in the open field test, as well as in the mechanical orofacial sensitivity. Animals that received stimulation for 6 h daily since p21 showed increased locomotor activity in the open field test. Animals that received stimulation for 2 h a day since p26 showed an increase in locomotor activity and a decrease in grooming behaviour in the open field test, in addition to a reduction in the number of entries in the closed arm of the elevated plus maze. Animals stimulated from p26 for 6 h daily increased the reaction time to the thermal stimulus. Animals that received stimulation for 2 h daily since p36 showed an increase in locomotor activity and a decrease in grooming behaviour in the open field test. Taken together, these findings suggest that audiovisual overstimulation during critical periods of brain development may have adverse effects compatible with hyperactivity in adulthood.

Protective effect of (-)-α-bisabolol on rotenone-induced toxicity in Drosophila melanogaster.

(-)-α-Bisabolol (BISA) is a sesquiterpene alcohol, which has several recognized biological activities, including anti-inflammatory, anti-irritant, and antibacterial properties. In the present study, we investigated the influence of BISA (5, 25, and 250 µmol/L) on rotenone (500 µmol/L)-induced toxicity in Drosophila melanogaster for 7 days. BISA supplementation significantly decreased rotenone-induced mortality and locomotor deficits. The loss of motor function induced by rotenone correlated with a significant change in stress response factors; it decreased thiol levels, inhibited mitochondria complex I, and increased the mRNA expression of antioxidant marker proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product. Taken together, our findings indicate that the toxicity of rotenone is likely due to the direct inhibition of complex I activity, resulting in a high level of oxidative stress. Dietary supplementation with BISA affected the expression of SOD mRNA only at a concentration of 250 µmol/L, and did not affect any other parameter measured. Our results showed a protective effect of BISA on rotenone-induced mortality and locomotor deficits in Drosophila; this effect did not correlate with mitochondrial complex I activity, but may be related to the antioxidant protection afforded by eliminating superoxide generated as a result of rotenone-induced mitochondrial dysfunction.

Effect of dietary supplementation with olive and sunflower oils on lipid profile and liver histology in rats fed high cholesterol diet.

OBJECTIVE: To compare the effects of high-monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) against the metabolic disorders elicited by a high-cholesterol diet (HC) in rats. METHODS: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil (cholesterol free diet) and 1% HC containing 12% olive oil (HC + OO) enriched with MUFA and 12% sunflower oil (HC + SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. RESULTS: Comparatively, rats treated with HC + OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC + SO diet (P < 0.05). Otherwise, HC + OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. CONCLUSIONS: HC + OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC + SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC + OO diet may have been caused by the delay in the FA release to the blood.

Antinociceptive action of Vanillosmopsis arborea in male mice.

OBJECTIVE: Vanillosmopsis arborea Baker (Asteraceae) has high economic value from Chapada to Araripe and its bark essential oil is a potential source of alpha-bisabolol. The present study aimed to elucidate the antinociceptive and antipruritic properties of the essential oil of V. arborea Baker (EOVA) in mice. MATERIALS AND METHODS: The antinociceptive activity was assessed using the capsaicin, glutamate, hot plate and cold allodynia tests. The antipuritic effects were also verified based on histamine-induced scratching behavior. RESULTS: EOVA reduced the paw licking induced by capsaicin, but not that induced by glutamate. The essential oil increased the latency time in the hot plate, attenuated the cold allodynia induced by acetone and inhibited histamine-induced scratching behavior. CONCLUSION: The experimental data demonstrated that EOVA showed central and peripheral antinociceptive activity and antipruritic effect.

Topical Antinociceptive Effect of Vanillosmopsis arborea Baker on Acute Corneal Pain in Mice.

This study aimed to assess the possible topical antinociceptive activity of Vanillosmopsis arborea Baker essential oil (EOVA) and to clarify the underlying mechanism, using the acute model of chemical (eye wiping) nociception in mice. EOVA (25 to 200 mg/kg; p.o. and topical) evidenced significant antinociception against chemogenic pain in the test model of formalin-induced neuroinflammatory pain. Local application of 5 M NaCl solution on the corneal surface of the eye produced a significant nociceptive behavior, characterized by eye wiping. The number of eye wipes was counted during the first 30 s. EOVA (25, 50, 100, and 200 mg/kg; p.o. and topical) significantly decreased the number of eye wipes. Naloxone, yohimbine, L-NAME, theophylline, glibenclamide, and ruthenium red had no effect on the antinociceptive effect of EOVA. However, ondansetron, p-chlorophenylalanine methyl ester (PCPA), capsazepine, prazosin, and atropine prevented the antinociception induced by EOVA. These results indicate the topical antinociceptive effect of EOVA and showed that 5-HT, α 1, TRPV1, and central muscarinic receptors might be involved in the antinociceptive effect of EOVA in the acute corneal model of pain in mice.

Attenuation of visceral nociception by α-bisabolol in mice: investigation of mechanisms.

BACKGROUND: We previously described the visceral antinociceptive property of α-bisabolol (BISA) in mouse models of visceral nociception induced by cyclophosphamide and mustard oil (MO). This study examined the effect of BISA in mouse models of visceral nociception induced by acetic acid, capsaicin, formalin, and the contribution of the nitric oxide system, α2, KATP, 5-HT3 and TRPV1 receptors to the effect of BISA on MO-evoked nociceptive behaviors. Mice were pretreated orally with BISA (50, 100 and 200 mg/kg) or vehicle, and the pain-related behavioral responses to intraperitoneal administration of acetic acid or intracolonic injection of MO were analyzed. RESULTS: BISA significantly suppressed the nociceptive behaviors in a dose-unrelated manner. The antinociceptive effect of BISA (50 mg/kg) was show to be glibenclamide resistant, but it was not blocked by pretreatment with the other antagonists tested. In the open-field test that detects sedative or motor abnormality, mice received 50 mg/kg BISA did not show any per se influence in ambulation frequency. CONCLUSIONS: However, their precise antinociceptive mechanisms of action have not been determined.

Ethanol-induced oxidative stress: the role of binaphthyl diselenide as a potent antioxidant.

It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. The protective effect of binaphthyl diselenide (NapSe)2 was investigated in ethanol (Etoh)-induced brain injury. Thirty male adult Wistar rats were divided randomly into five groups of six animals each and treated as follows: (1) The control group received the vehicle (soy bean oil, 1 mL/kg, p.o.). (2) Ethanol group of animals was administered with ethanol (70% v/v, 2 mL/kg, p.o.). (3) (NapSe)2 1 mg/kg, 1 mL/kg plus ethanol 70% (v/v, 2 mL/kg, p.o. (5) (NapSe)2 10 mg/kg, 1 mL/kg) plus ethanol 70% (v/v, 2 mL/kg, p.o). After acute treatment, all rats were sacrificed by decapitation. Evidence for oxidative stress in rat brain was obtained from the observed levels of thiobarbituric acid reactive species, of non-protein thiol (NPSH) groups, and of ascorbic acid, as well as from the activities of catalase (CAT) and of superoxide dismutase (SOD). (NapSe)2 compensated the deficits in the antioxidant defense mechanisms (CAT, SOD, NPSH, and ascorbic acid), and suppressed lipid peroxidation in rat brain resulting from Etoh administration. It was concluded that ethanol exposure causes alterations in the antioxidant defense system and induces oxidative stress in rat brain. (NaPSe)2 at 5 mg/kg restored the antioxidant defenses in rat brain and mitigated the toxic effects of alcohol, suggesting that could be used as a potential therapeutic agent for alcohol-induced oxidative damage in rat brain.

Antioxidant effect of Stryphnodendron rotundifolium Martius extracts from Cariri-Ceará State (Brazil): potential involvement in its therapeutic use.

Stryphnodendron rotundifolium is a phytotherapic used in the northeast of Brazil for the treatment of inflammatory processes which normally are associated with oxidative stress. Consequently, we have tested the antioxidant properties of hydroalcoholic (HAB) and aqueous extracts (AB) from the bark and aqueous extract (AL) from the leaves of Stryphnodendron rotundifolium to determine a possible association between antioxidant activity and the popular use of this plant. Free radical scavenger properties were assessed by the quenching of 1',1'-diphenil-2-picrylhydrazyl (DPPH) and the calculated IC(50) were: HAB = 5.4 ± 0.7, AB = 12.0 ± 2.6, and AL = 46.3 ± 12.3 µg/mL. Total phenolic contents were: HAB = 102.7 ± 2.8, AB = 114.4 ± 14.6, and AL = 93.8 ± 9.1 µg/mg plant). HPLC/DAD analyses indicated that gallic acid, catechin, rutin and caffeic acid were the major components of the crude extracts of S. rotundifolium. Plant extracts inhibited Fe(II)-induced lipid peroxidation in brain homogenates. Iron chelation was also investigated and only HBA exhibited a weak activity. Taken together, the results suggest that S. rotundifolium could be considered an effective agent in the prevention of diseases associated with oxidative stress.

O óleo essencial do caule de Vanillosmopsis arborea atenua a dor visceral em camundongos / Attenuation of visceral pain in mice by the essential oil from Vanillosmopsis arborea bark

BACKGROUND AND OBJECTIVES: Vanillosmopsis arborea Baker (Asteraceae) has high economic value and anti-inflammatory properties due the presence of alpha bisabololin its bark essential oil. Keeping in view the highcontent of ?-bisabolol in Vanillosmopsis arborea (EOVA) bark essential oil, the aim of our study was to determinewhether EOVA mitigates visceral nociception induced bydifferent noxious gents.METHOD: Mice (n = 8) were pretreated orally with EOVA (100, 200 e 400 mg/kg) or vehicle, and pain-related behavioral responses to intraperitoneal cyclophosphamide (CPM 400 mg/kg), intracolonic mustard oil (MO0.75%) or capsaicin (CAP 0.3%) were analyzed.RESULTS: Animals that received CFM, OM or CAP presented spontaneous nociceptive behaviors that were signifi cantly suppressed by EOVA. CONCLUSION: These fi ndings point to visceral antinociceptive properties of EOVA suggesting the potential use of Vanillosmopsis arborea to treat pain associated to gastrointestinal disorders

JUSTIFICATIVA E OBJETIVOS: Vanillosmopsis arborea Baker (Asteraceae) de reconhecido valor econômico que possui propriedades anti-inflamatórias provenientes do sesquiterpeno alfa-bisabolol, presente em teores elevados no óleo essencial de sua madeira. Considerando-se o alto teor de ?-bisabolol no óleo essencialdo caule de Vanillosmopsis arborea (OEVA). O objetivo deste estudo foi determinar o efeito do OEVA na nocicepção visceral induzida por diversos agentes irritantes.MÉTODO: Camundongos (n = 8) foram pré-tratados por via oral com EOVA (100, 200 e 400 mg/kg) ou veículo e as respostas comportamentais devido a administração de ciclofosfamida (CFM 400 mg/kg; por via intraperitoneal), óleo de mostarda (OM 0,75%; intracolônico) ou capsaicina (CAP 0,3%; intracolônica) foram registradas.RESULTADOS: Os animais que receberam CFM, OM ou CAP manifestaram comportamentos nociceptivos espontâneos que foram significativamente suprimidos nosgrupos tratados com OEVA.CONCLUSÃO: Estes achados apontam a propriedade antinociceptiva visceral do óleo essencial do caule de Vanillosmopsis arborea indicando o uso potencial no alívio da dor associada às desordens gastrintestinais.