Investigation on the Anticonvulsant Potential of Luteolin and Micronized Luteolin in Adult Zebrafish (Danio rerio).

Epilepsy affects around 50 million people worldwide, and an important number of patients (30%) fail to respond to any available antiepileptic drug. Previous studies have shown that luteolin presents a promising potential as an anticonvulsant. On the other hand, different studies showed that luteolin does not promote anticonvulsant effects. Therefore, there is a lack of consensus about the use of luteolin for seizure control. Luteolin low bioavailability could be a limiting factor to obtain better results. Attractively, micronization technology has been applied to improve flavonoids bioavailability. Thus, the present study aimed to investigate the effects of luteolin on its raw form and micronized luteolin in a PTZ-induced seizure model in adult zebrafish (Danio rerio). Our results demonstrate that luteolin and micronized luteolin did not block PTZ-induced seizures in adult zebrafish. Also, luteolin and micronized luteolin did not provoke behavioral changes. Finally, our results show that 24 h after seizure occurrence, no changes were detected for p70S6Kb, interleukin 1ß, and caspase-3 transcript levels. Altogether, we failed to observe an anticonvulsant potential of luteolin in adult zebrafish, even in its micronized form. However, we recommend new studies to investigate luteolin benefits in epilepsy.

Micronized Resveratrol Shows Anticonvulsant Properties in Pentylenetetrazole-Induced Seizure Model in Adult Zebrafish.

Epilepsy affects 50 million people around the world, and the patients experience cognitive, psychological and social consequences. Despite the considerable quantity of antiepileptic drugs available, 30% of patients still suffer in seizure. Therefore, the advance in therapeutic alternatives is mandatory. Resveratrol has been attracting the attention of many researchers because of its pharmacological potential. However, despite its neuroprotective and anti-epileptic effects, clinical resveratrol use is impaired by its low bioavailability. Here, we applied the supercritical fluid micronization technology (SEDS) to overcome this deficit, and investigated the anticonvulsant potential of micronized resveratrol in a PTZ-induced seizure model in adult zebrafish (Danio rerio). SEDS permits obtaining significantly reduced particle size with a fine size distribution in comparison with the starting material. It can improve the pharmacotherapeutic efficacy. Our data showed that micronized resveratrol decreased the occurrence of the tonic-clonic seizure stage and slowed the development of the seizures in a similar manner of diazepam. Non-processed resveratrol was not able to protect the animals. Furthermore, diazepam decreased the locomotion and exploratory behavior. Differently from diazepam, the micronized resveratrol did not induce behavioral adverse events. In addition, our data showed that the PTZ-induced seizures increased the c-fos transcript levels following the neural excitability. However, the increase in c-fos levels was prevented by micronized resveratrol. In conclusion, our results demonstrate that the micronized resveratrol shows anticonvulsant effect, like the classical antiepileptic drug diazepam in a PTZ-induced seizure model. Excitingly, different from diazepam, micronized resveratrol did not provoke behavioral adverse events.

Micronized resveratrol shows promising effects in a seizure model in zebrafish and signalizes an important advance in epilepsy treatment.

Resveratrol is a natural non-flavonoid polyphenolic that has been emerging in epilepsy treatment. Despite its pharmacological properties, the poor bioavailability of resveratrol has been an important barrier that hinders its application as an anticonvulsant. The aim of this work was to improve resveratrol's anticonvulsant effects by micronizing this compound through supercritical fluid micronization technology, which promotes an increase of the particles' surface area and allows significantly reduced particle size to be obtained. We obtained commercial and micronized resveratrol and investigated the anticonvulsant effects of resveratrol as commercially found and micronized resveratrol in a pentylenetetrazole-induced seizure model in zebrafish (Danio rerio) larvae. Diazepam was used as the positive control. Also, animals had their locomotor and exploratory activity analyzed 24 h after the seizure occurrence. The occurrence of the tonic-clonic seizure stage was only prevented by diazepam and micronized resveratrol, unlike the non-processed compound. The seizure development was significantly slowed by diazepam and micronized resveratrol, while non-micronized resveratrol was not able to increase the latency of seizure stages. In addition, diazepam and micronized resveratrol prevented the deleterious effects of pentylenetetrazole-induced seizures on animals' locomotor and exploratory behaviour. Obtained data demonstrates that the micronization process potentiates the anticonvulsant effect of resveratrol. Micronized resveratrol achieved a similar effect to the classical drug diazepam, with the benefit that it may be a safe drug candidate to be used during the neurodevelopmental stage.

Natural Bioenhancers in Drug Delivery: An Overview.

When the bioavailability of a drug increases, a corresponding increase in the levels of that drug in the bloodstream occurs. With this, drug efficacy is augmented and the dosage required to yield a specific therapeutic effect diminishes comparably. Until recently, only a few methods have proven effective in enhancing drug bioavailability, among which are the disaggregation of micronized molecules, the use of timedrelease and topical preparations, mechanization, polymorph and crystal form selection, drug solubilisation, and the use of nanotechnology. (Though still at the experimental stage, nanotechnology promises to become a powerful pharmacological tool in the future.) Bioenhancers are agents not possessing any inherent therapeutic effects but that, when combined with active drugs, potentiate the pharmacological effects of those drugs. Hence the current article describes the enhancement of the bioavailability of drug molecules through the utilization of natural bioenhancers.

Bromatological and mycotoxin analysis on soybean meal before and after the industrial process of micronization / Análise bromatológica e micotoxicológica do farelo de soja antes e após processo industrial de micronização

Aflatoxins, fumonisins and zearalenone take part of the most studied mycotoxin groups due to their toxic effects on animal and human health. This research evaluated samples of soybeans meal used in animal food industry. A hundred and twenty one soybean meal samples were analyzed, so that 66 were analyzed before the industrial processing of micronization and 55 after it. The bromatological average of samples before micronization showed the following answers: 12.4% moisture; 46.4% protein; 79.5% protein solubility; 5.9% ash content; 2.2% fat; 4.3% fiber and 0.02 (ΔpH) of urease activity. The samples of micronization soybean meal showed 7.0% average values for moisture and 48.6% for crude protein. The mycotoxin levels were low in natura soybean meal; therefore, average values were 0.5μg kg-1, 29.6μg kg-1 and 56.8μg kg-1 for aflatoxin, zearelenone and fumonisin, respectively. After micronization, the average values for the studied samples were 1.3μg kg-1, 67.5μg kg-1 and 89.1μg kg-1, respectively for the same mycotoxins. The results for bromatological and mycotoxin analyses indicate similarity with the established patterns according to the Brazilian Compendium for Animal feed and reference literature. However, at least one of the three studied mycotoxin was detected in all of the analyzed samples and there was greater contamination of soybeans meal after the micronization process.

Aflatoxinas, fumonisinas e zearalenona pertencem aos grupos de micotoxinas mais estudados, devido aos efeitos tóxicos provocados na saúde animal e humana. O presente estudo avaliou amostras de farelo de soja utilizado em uma indústria de nutrição animal. Foram analisadas 121 amostras de farelo de soja, sendo 66 antes do processo industrial de micronização e 55 após o processamento. A composição bromatológica média das amostras antes da micronização apresentou 12,4% de umidade; 46,4% de proteína; 79,5% de solubilidade proteica; 5,9% de cinzas; 2,2% de gordura; 4,3% de fibra e 0,02 (ΔpH) de atividade ureásica. As amostras de farelo de soja micronizado apresentaram valores médios de 7.0% para umidade e 48,6% para proteína bruta. Os resultados apresentaram baixos níveis de micotoxinas no farelo de soja "in natura", detectando valores médios para aflatoxina, zearalenona e fumonisina de 0,5μg kg-1, 29,6μg kg-1e 56,8μg kg-1, respectivamente. Após a micronização, as amostras apresentaram valores médios de 1,3μg kg-1, 67,5μg kg-1 e 89,1μg kg-1, respectivamente, para as mesmas micotoxinas. Os resultados das análises bromatológicas e de micotoxinas evidenciaram conformidade com os padrões estabelecidos pelo Compêndio Brasileiro de Alimentação Animal e literatura de referência. Entretanto, detectou-se a presença de, no mínimo, uma das três micotoxinas pesquisadas em todas as amostras analisadas e uma maior contaminação no farelo de soja após o processo de micronização.

Bromatological and mycotoxin analysis on soybean meal before and after the industrial process of micronization / Análise bromatológica e micotoxicológica do farelo de soja antes e após processo industrial de micronização

Aflatoxins, fumonisins and zearalenone take part of the most studied mycotoxin groups due to their toxic effects on animal and human health. This research evaluated samples of soybeans meal used in animal food industry. A hundred and twenty one soybean meal samples were analyzed, so that 66 were analyzed before the industrial processing of micronization and 55 after it. The bromatological average of samples before micronization showed the following answers: 12.4% moisture; 46.4% protein; 79.5% protein solubility; 5.9% ash content; 2.2% fat; 4.3% fiber and 0.02 (pH) of urease activity. The samples of micronization soybean meal showed 7.0% average values for moisture and 48.6% for crude protein. The mycotoxin levels were low in natura soybean meal; therefore, average values were 0.5g kg-1, 29.6g kg-1 and 56.8g kg-1 for aflatoxin, zearelenone and fumonisin, respectively. After micronization, the average values for the studied samples were 1.3g kg-1, 67.5g kg-1 and 89.1g kg-1, respectively for the same mycotoxins. The results for bromatological and mycotoxin analyses indicate similarity with the established patterns according to the Brazilian Compendium for Animal feed and reference literature. However, at least one of the three studied mycotoxin was detected in all of the analyzed samples and there was greater contamination of soybeans meal after the micronization process.(AU)

Aflatoxinas, fumonisinas e zearalenona pertencem aos grupos de micotoxinas mais estudados, devido aos efeitos tóxicos provocados na saúde animal e humana. O presente estudo avaliou amostras de farelo de soja utilizado em uma indústria de nutrição animal. Foram analisadas 121 amostras de farelo de soja, sendo 66 antes do processo industrial de micronização e 55 após o processamento. A composição bromatológica média das amostras antes da micronização apresentou 12,4% de umidade; 46,4% de proteína; 79,5% de solubilidade proteica; 5,9% de cinzas; 2,2% de gordura; 4,3% de fibra e 0,02 (pH) de atividade ureásica. As amostras de farelo de soja micronizado apresentaram valores médios de 7.0% para umidade e 48,6% para proteína bruta. Os resultados apresentaram baixos níveis de micotoxinas no farelo de soja "in natura", detectando valores médios para aflatoxina, zearalenona e fumonisina de 0,5g kg-1, 29,6g kg-1e 56,8g kg-1, respectivamente. Após a micronização, as amostras apresentaram valores médios de 1,3g kg-1, 67,5g kg-1 e 89,1g kg-1, respectivamente, para as mesmas micotoxinas. Os resultados das análises bromatológicas e de micotoxinas evidenciaram conformidade com os padrões estabelecidos pelo Compêndio Brasileiro de Alimentação Animal e literatura de referência. Entretanto, detectou-se a presença de, no mínimo, uma das três micotoxinas pesquisadas em todas as amostras analisadas e uma maior contaminação no farelo de soja após o processo de micronização.(AU)

Impact of micronized starfruit (Averrhoa carambola L.) fiber concentrate on lipid metabolism in mice.

The objective of this study was to evaluate the effect of micronized insoluble fiber from starfruit bagasse as an ingredient of a functional food (FF) or as micronized insoluble fiber-rich fraction (IFRF) and its effects in vivo on lipids metabolism in a murine model. Experimental animals were divided in four isoproteic (15.8%) treatments differing on the fiber and cholesterol level used. The micronized IFRF particle size ranged from 37.5 to 149 µm. Treatments with added IFRF and those including the FF lowered serum triacylglycerols, total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL) concentrations (IFRF: 14.2, 25.4, 55.06, and 12.18%, respectively; FF: 30.18, 39.47, 35.11, and 43.18%, respectively). IFRF produced the overall highest serum hypolipidemic effect and prevented the development of non-alcoholic fatty liver. Both the IFRF and the FF exhibited hypolipidemic effects that suggest a potential role of starfruit insoluble fiber as a component of FFs aimed against cardiovascular diseases.

Micronized benzoic acid decreases the concentration necessary to preserve acidic beverages against Alicyclobacillus.

AIMS: The aim of this study was a challenge testing the effect of lower concentrations of micronized benzoic acid against two strains of Alicyclobacillus. METHODS AND RESULTS: The effect of micronized benzoic acid was compared with the usual levels of untreated commercial sodium benzoate and benzoic acid, at the challenge temperature of 45°C. The size of the benzoic acid particles was determined by scanning electron microscopy. The diameter of the micronized particles was around 10 µm with a maximum length of 200 µm, while the untreated preservative structures were irregular with lengths up to 500 µm. A continuous bactericidal effect against two Alicyclobacillus strains, throughout the 28-day period, was observed with 50 mg l(-1) of micronized benzoic acid, but when the untreated preservative was used, the same lethal effect was not achieved even after doubling its concentration. CONCLUSIONS: The antimicrobial activity of benzoic acid was improved by micronization. The process proved to be an effective alternative to reduce the benzoic acid concentration necessary to ensure stability of an orange juice matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: The results proved that the micronization process represents an alternative to reduce the required food preservative concentration; this method increased the stability of the compound, which maintains its bioavailability.

Composição química e valor nutritivo da soja crua e submetida a diferentes processamentos térmicos para suínos em crescimento / Chemical composition and nutritive value of thermal processed soybean products for growing pigs

Um ensaio de metabolismo foi conduzido para avaliar a digestibilidade de nutrientes e valores energéticos de grãos de soja processados no calor para suínos em crescimento. Foram utilizados 20 suínos machos castrados, mestiços, com peso inicial médio de 37,67± 3,33kg. Adotou-se delineamento inteiramente ao acaso, com cinco tratamentos e quatro repetições. Os alimentos avaliados foram farelo de soja, soja semi-integral extrusada, soja integral expandida e soja integral micronizada, os quais substituíram em 25 por cento a dieta-referência. Os valores de ED e dos coeficientes de digestibilidade aparente da EB, PB, MS e EE para os alimentos testados foram: 3583kcal/kg, 85,2 por cento, 90,8 por cento, 85,7 por cento e 69,3 por cento para o farelo de soja; 4065kcal/kg, 83,6 por cento, 86,1 por cento, 81,9 por cento e 81,5 por cento para a soja semi-integral extrusada; 3803kcak/kg, 75,2 por cento, 73,9 por cento, 74,4 por cento e 80,4 por cento para a soja integral expandida; 5272kcal/kg, 95,3 por cento, 95,2 por cento, 93,2 por cento e 94,3 por cento para a soja integral micronizada. A expansão foi inadequada para a soja integral, que apresentou os piores valores de digestibilidade. Os processamentos de extrusão e micronização das sojas semi-integral e integral, respectivamente, foram eficientes na inativação dos fatores antinutricionais e na melhoria de suas digestibilidades, sendo que a micronização mostrou-se superior aos demais processamentos. (AU)

A metabolism trial was conducted to evaluate the digestibility rate and energy values of thermal processed soybean for growing pigs. Twenty barrows with an initial average weight of 37.67± 3.33kg were used in a completely randomized design with five treatments and four replicates. The treatments consisted in a reference diet and four experimental diets. The feedstuffs evaluated were soybean meal, extruded semi-integral soybean, expanded integral soybean and micronized integral soybean. These ingredients replaced 25% of the reference diet. The values of digestibility energy and apparent digestibility rates of crude energy, crude protein, dry matter and ether extract of the feeds were: 3583kcal/kg, 85.2%, 90.8%, 85.7% and 69.3% for soybean meal; 4065kcal/kg, 83.6%, 86.1%, 81.9% and 81.5% for extruded semi-integral soybean; 3803kcal/kg, 75.2%, 73.9%, 74.4% and 80.4% for expanded integral soybean; 5272kcal/kg, 95.3%, 95.2%, 93.2% and 94.3% for micronized integral soybean. The expansion process was not adequate for integral soybean, which showed the worst digestibility rate. The extrusion and the micronization processes of semi-integral and integral soybean respectively, were efficient to inactivate the antinutritional factors and to improve the digestibility. The results obtained with the micronization process were better than those of the others thermal processes. (AU)