RESUMO
Environmental challenges are integrated in the inmunoneuroendocrine interplay, impacting the immune system of the challenged individuals, and potentially implying transgenerational effects on their offspring. This study addressed whether dietary supplementation with thymol can modulate the immune response of adult Japanese quail when simultaneously exposed to an inoculum of inactivated Salmonella Enteritidis and a chronic heat stress (CHS). We also evaluated whether the experienced situations by adults can affect the immune response of their undisturbed offspring. In the parental generation, supplemented quail exposed to CHS had a higher inflammatory response and similar values of the heterophil/lymphocyte (H/L) ratio than those that were not supplemented. In their offspring, those chicks whose parents were exposed to CHS showed higher inflammatory response and lower antibody production. Regarding the H/L ratio, chicks whose parents were supplemented showed lower H/L ratio values. Dietary supplementation with thymol partially and positively modulated the inflammatory response and avoided H/L ratio alteration in the parental generation exposed to high environmental temperatures, suggesting these adults were better at dealing with the challenge. The lower H/L ratio values in the offspring suggests that chicks are more capable to deal with potential stressful situations associated with conventional breeding conditions.
Assuntos
Ração Animal , Doenças das Aves/prevenção & controle , Coturnix/imunologia , Transtornos de Estresse por Calor/veterinária , Salmonella enteritidis/imunologia , Timol/administração & dosagem , Animais , Doenças das Aves/sangue , Doenças das Aves/imunologia , Doenças das Aves/microbiologia , Coturnix/microbiologia , Feminino , Transtornos de Estresse por Calor/sangue , Transtornos de Estresse por Calor/imunologia , Transtornos de Estresse por Calor/prevenção & controle , Temperatura Alta/efeitos adversos , Contagem de Linfócitos , Linfócitos/imunologia , Masculino , Exposição Materna , Neuroimunomodulação/efeitos dos fármacos , Óvulo/imunologia , Exposição Paterna , Fatores SexuaisRESUMO
The search of novel strategies for anthelmintic control is a crucial need considering the widespread increase in resistant parasitic populations in livestock. Bioactive phytochemicals may contribute to improve parasite control by enhancing the effect of existing anthelmintic drugs. The aim of the current work was to evaluate the in vivo and in vitro pharmaco-chemical interaction and the in vivo efficacy of the combination of albendazole (ABZ) with thymol (TML) in lambs naturally infected with resistant gastrointestinal nematodes. Thirty (30) lambs were allocated into three experimental groups. Each group was treated orally with either ABZ (5â¯mg/kg), TML (150â¯mg/kg, twice every 24â¯h) or the co-administration of both compounds. Blood samples were collected between 0 and 51â¯h post-treatment and TML, ABZ and its metabolites were measured by HPLC. Individual faecal samples were collected at days -1 and 14 post-treatment to perform the faecal egg count reduction test. Additionally, the effect of TML on the sulphoreduction and sulphonation of ABZ sulphoxide was assessed in vitro using ruminal content and liver microsomes, respectively. The metabolism of TML in the ruminal content was very low and the monoterpene exhibited a low degree of association with the particulate phase of the ruminal content. No changes in the pharmacokinetic behavior of ABZ sulphoxide were observed in the presence of the natural product (TML). In contrast, the ABZ sulphone Cmax and AUC were lower (P 0.002 and 0.001 respectively) in the co-administered animals (0.16⯱â¯0.07⯵g/mL and 3.63⯱â¯1.21⯵g.h/mL) compared with those that received ABZ alone (0.45⯱â¯0.15⯵g/mL and 9.50⯱â¯2.84⯵g.h/mL). TML was detected in the bloodstream between 1 and 48â¯h post-treatment, which indicates the time of target nematodes being exposed to the bioactive monoterpene. However, the in vivo efficacy of TML was 0% and the presence of this terpene did not increase the efficacy of ABZ. The presence of TML significantly inhibited the ruminal sulphoreduction (P 0.001) and the hepatic sulphonation (P 0.001) of ABZ sulphoxide. These observations point out that in vivo pharmaco-parasitological studies are relevant to corroborate the adverse kinetic/metabolic interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics.
Assuntos
Albendazol/administração & dosagem , Resistência a Medicamentos/efeitos dos fármacos , Gastroenteropatias/tratamento farmacológico , Helmintíase Animal/tratamento farmacológico , Doenças dos Ovinos/tratamento farmacológico , Timol/administração & dosagem , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/farmacologia , Quimioterapia Combinada , Gastroenteropatias/parasitologia , Helmintíase Animal/parasitologia , Compostos Fitoquímicos/farmacologia , Ovinos , Doenças dos Ovinos/parasitologia , Resultado do TratamentoRESUMO
The objective of this study was to determine whether curcumin and a commercial microencapsulated phytogenic supplement containing thymol, cinnamaldehyde and carvacrol in broiler chicken feed would improve health and meat quality (fatty acid profile), as well as to determine the coccidiostatic and bactericidal potential of the additives. The broiler chickens were divided into five groups: NC - negative control feed; PC - positive control; CU - with 50 mg/kg of curcumin, PHY - 100 mg/kg phytogenic; and PHY + CU, a combination of both additives at 50 mg/kg (curcumin) and 100 mg/kg (phytogenic). We observed significantly higher levels of total proteins associated with increased circulating globulins, as well as lower levels of uric acid, cholesterol and triglycerides in the PHY + CU group than in the NC. There were significantly fewer oocysts in birds supplemented with additives in the NC group on day 21; on day 35, the NC, PHY and PHY + CU groups had significantly lower counts than the PC and CU groups; however, at 44 days, the lowest counts were in PC group. The bacterial counts were significantly lower on day 21 in all groups that received additives than those of the control group; however, at 44 days, the bacterial and Escherichia coli counts in these groups were significantly higher than those of the control. Curcumin with or without phytogenic agent improved meat quality, with increased antioxidant levels and reduction of lipid peroxidation. There were significantly lower total saturated fatty acid levels and significantly greater monounsaturated/polyunsaturated fatty acid levels in broilers that consumed additives individually and in combination. The combination of additives significantly increased the crypt/villus ratio, a marker of improved intestinal health and performance. Additives potentiated their individual effects, suggesting they can replace conventional growth promoters without compromising health, intestinal mucosa or meat quality.
Assuntos
Acroleína/análogos & derivados , Infecções Bacterianas/veterinária , Coccidiose/veterinária , Curcumina/administração & dosagem , Cimenos/administração & dosagem , Carne/análise , Doenças das Aves Domésticas/prevenção & controle , Timol/administração & dosagem , Acroleína/administração & dosagem , Ração Animal/análise , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Infecções Bacterianas/fisiopatologia , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Galinhas/microbiologia , Galinhas/parasitologia , Coccídios/efeitos dos fármacos , Coccídios/genética , Coccídios/crescimento & desenvolvimento , Coccidiose/metabolismo , Coccidiose/parasitologia , Coccidiose/prevenção & controle , Suplementos Nutricionais/análise , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/parasitologiaRESUMO
We determined whether thymol supplementation of would minimize the negative effects of Aeromonas hydrophila infection on branchial energy metabolism, weight loss and mortality in grass carp (Ctenopharyngodon idella). We found that the infected fish all died, while 62.5% of those supplemented with 100 mg/kg thymol survived. Cytosolic and mitochondrial creatine kinase (CK) activities, as well as adenylate kinase (AK) and pyruvate kinase (PK) activities were significant lower in gills of A. hydrophila-infected fish than those of the control group, and adenosine triphosphate (ATP) levels were significant lower in the infected group. Finally, branchial reactive oxygen species (ROS) were significant higher in A. hydrophila-infected fish than in the control group. Supplementation with 100 and 300 mg thymol/kg diet prevented inhibition of branchial cytosolic and mitochondrial CK activities caused by infection, and also inhibited the reduction of branchial ATP levels. Supplementation with 100, 200 and 300 mg thymol/kg prevented the inhibition of branchial AK and PK activities induced by aeromonosis. Supplementation of 100 mg thymol/kg prevented weight loss after A. hydrophila infection. These data suggest that supplementation with 100 mg thymol/kg exerts potent bactericidal properties and augments longevity. Supplementation at all concentrations of thymol prevented A. hydrophila-induced branchial bioenergetics; nevertheless, higher concentrations were associated with side-effects.
Assuntos
Aeromonas hydrophila/fisiologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Timol/administração & dosagem , Trifosfato de Adenosina/metabolismo , Ração Animal/análise , Animais , Carpas/crescimento & desenvolvimento , Carpas/metabolismo , Carpas/microbiologia , Suplementos Nutricionais/análise , Metabolismo Energético/efeitos dos fármacos , Doenças dos Peixes/metabolismo , Doenças dos Peixes/mortalidade , Doenças dos Peixes/fisiopatologia , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Espécies Reativas de Oxigênio/metabolismoRESUMO
Solid inclusion complexes with cyclodextrins (CD) may be used to overcome volatility and solubility problems of essential oils of pharmacological interest. However, they lack the many dermatological advantages of lipid nanoparticles. This study intends to evaluate the ability of nanostructured lipid carriers (NLC) to encapsulate hydroxypropyl-ß-cyclodextrin inclusion complexes of Lippia origanoides essential oil (EO) and to maintain the desirable aspects of lipid colloids interaction with the skin, specifically follicular accumulation and controlled delivery. CD and NLC were also evaluated separately. Thymol (TML) was used as the essential oil marker and to produce control formulations. As expected, CD alone, though effective in overcoming volatility and low aqueous solubility of TML, were ineffective in controlling marker release (Ë50% of EO released after 3â¯h, Hixson-Crowell kinetics). Even though NLC controlled drug release (Ë20% EO released after 12â¯h, zero-order kinetics) enabling TML penetration into the skin (> 40⯵g/cm2after 12â¯h), NLC alone were not efficient in preventing TML volatility, especially at higher temperatures (calculated shelf-life of 2 days at 35⯰C). The combined approach resulted in a synergistic effect (Ë20% EO released after 12â¯h; shelf life of 6 days). The lack of statistical difference of TML skin penetration from NLC and NLC-CD suggests the developed system maintained all skin interaction aspects of lipid colloids, including follicular accumulation forming a depot for controlled delivery. In conclusion, lipid nanoparticles demonstrated to be promising carriers for inclusion complexes of this particular volatile essential oil.
Assuntos
Ciclodextrinas/administração & dosagem , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Óleos Voláteis/administração & dosagem , Administração Cutânea , Animais , Ciclodextrinas/química , Ciclodextrinas/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Nanopartículas/ultraestrutura , Óleos Voláteis/química , Óleos Voláteis/farmacocinética , Pele/metabolismo , Solubilidade , Suínos , Temperatura , Timol/administração & dosagem , Timol/química , Timol/farmacocinética , VolatilizaçãoRESUMO
Phytogenic additives such as thymol are encountering growing interest in the poultry industry. However, there are still questions concerning dynamics of their bioavailability, biological action, optimal dosage and duration of supplementation needed to achieve meaningful effects, as well as persistence of induced changes after supplement withdrawal. We studied the link between the dynamics of free thymol concentration and the changes in fatty acids composition in quail egg yolk, both during a month-long chronic dietary supplementation and after 3 weeks of supplement withdrawal (post-supplementation). Fifty, 85 days-old, female quail of homogeneous body weights (251±1g) in egg-laying peak were used. To evaluate potential dose-dependent effects, three increasing doses 2, 4, and 6.25 g of thymol/kg of feed (THY2, THY4 and THY6, respectively) and two controls were evaluated (n = 10). In parallel, we assessed the concomitant changes in free thymol excretion, potential liver histopathological changes, and birds´ performance traits. Egg yolk and droppings show a dose-dependent increase in THY concentration after 9 days of supplementation and a decrease after post-supplementation. In egg yolk, these changes were accompanied by reduced saturated fatty acid concentrations achieved by 28 days of supplementation in THY2 and 14 days of supplementation in THY4 and THY6. However, after post-supplementation the aforementioned effect disappeared in THY2 but not in THY4 and THY6. While THY2 failed to increase polyunsaturated fatty acids, THY4 and THY6 increased polyunsaturated fatty acids by day 14 of supplementation and remained increased after post-supplementation. Fatty acids changes induced by thymol are consistent with improved nutritional quality of eggs. No treatment effects were observed in liver histopathology and female performance. Findings suggest that both dose of thymol and duration of supplementation modulate thymol and fatty acids concentrations in egg yolk and thymol concentration in droppings. Furthermore, the persistence of those effects after post-supplementation period is also a dose-dependent phenomenon.
Assuntos
Ração Animal/análise , Coturnix/fisiologia , Suplementos Nutricionais , Gema de Ovo/metabolismo , Ácidos Graxos/metabolismo , Oviposição/fisiologia , Timol/administração & dosagem , Animais , Anti-Infecciosos/administração & dosagem , Disponibilidade Biológica , Feminino , Oviposição/efeitos dos fármacosRESUMO
Chronic heat stress (CHS) exposure negatively impairs avian' immunoneuroendocrine interplay. Thymol has shown several bioactive properties including antioxidant, bactericidal, antifungal and gamma-aminobutyric acid modulator activities. Indeed, supplementation with thymol has been used with positive effects on poultry production and immune-related variables. This study evaluates whether a thymol dietary supplementation can be used as a new functional feed strategy to mitigate CHS deleterious effects on endocrine, biochemical and immune-related variables. Starting at 100 days of age, 24 fully adult Japanese quail were fed with a diet supplemented with thymol (≈80 mg/quail per day) and other 24 quail remained non-supplemented (control diet). Between 119 and 127 days of age, half of the quail within those groups were submitted to a CHS by increasing environmental temperature from 24°C to 34°C during the light phase and the other half remained at 24°C (non-stressed controls). A period of 3 days after CHS ended (during the recovery period), corticosterone, albumin, total proteins and globulins and glucose concentrations, inflammatory response, antibody production and heterophil to lymphocyte (H/L) ratio were assessed. No differences between groups were found in basal corticosterone concentrations. Total proteins, total globulins and glucose concentrations were found elevated in the previously CHS group compared with their control counterparts. Regardless of the previous CHS exposure, thymol supplementation increased albumin concentrations and inflammatory responses and decreased antibody titers. An interaction between thymol supplementation and prior CHS exposure was found on the H/L ratio. Quail previously exposed to CHS and supplemented with thymol showed similar H/L values than their control non-stressed counterparts, suggesting that thymol has a stress preventive effect on this variable. The present findings together with the already reported thymol bioactive properties, suggest that feed supplementation with this compound could be a useful strategy to help overcoming some of the CHS induced alterations.
Assuntos
Coturnix/fisiologia , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico/efeitos dos fármacos , Timol/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Transtornos de Estresse por Calor/prevenção & controle , Timol/administração & dosagemRESUMO
Consumer concern on the quality of products and animal welfare has greatly increased during the past decades. Dietary synthetic antibiotic products used as growth promoters have been restricted or banned in many countries. Edible plants, essential oils, or their main components were suggested as natural feed supplements to improve growth, products' quality, and welfare-related parameters. Thymol (THY), a main component of oregano essential oil, has been proved as an effective antimicrobial and antioxidant compound. Tocopherol (TOC) evidenced antioxidant activity with potential as a growth promoter and a synergic antioxidant activity between TOC and ascorbyl palmitate (AP) has also been reported. Herein, we evaluated whether broiler diet supplementation with THY, and THY with a formulation mix containing TOC and AP (1:0.5:0.5, respectively) have potential as growth enhancers under commercial conditions. Potential protective effects against foot pad dermatitis and hock burns were also evaluated. Newly hatched male broiler chicks with similar body weight (BW) were randomly assigned to 1 of 7 groups (4 replicates each) as follows: Basal (no feed supplements added), Promotor (Basal + 6.26 µmol flavomycin/kg feed), BHT (Basal + 1.33 mmol of buthylated hidroxytoluene (BHT)/kg feed), Prom-BHT (Basal + 6.26 µmol flavomycin/kg feed + 1.33 mmol of BHT/kg feed), TOC-AP (Basal + 0.67 mmoles of TOC + 0.67 mmoles of AP/kg feed), THY (Basal + 1.33 mmoles of THY/kg feed), and THY-TOC-AP (Basal + 0.67 mmoles of THY + 0.67 mmoles of a mix 1:1 of TOC-AP). Along 7 wk, BW, feed intake, and feed conversion ratio were evaluated. Skin injuries were assessed at 35 d of age. At the end of the study (42 d), compared to Basal group, similarly enhanced final BW were observed in all groups but TOC-AP. No main differences between groups were detected in feed intake, feed conversion ratio, or skin injuries. Findings suggest that THY itself or in combination with TOC-AP may have value as a natural growth enhancer alternative for broilers.
Assuntos
Ração Animal/análise , Ácido Ascórbico/análogos & derivados , Galinhas , Substâncias de Crescimento/farmacologia , Timol/farmacologia , alfa-Tocoferol/farmacologia , Animais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Dieta/veterinária , Suplementos Nutricionais/análise , Doenças do Pé/prevenção & controle , Doenças do Pé/veterinária , Masculino , Doenças das Aves Domésticas/prevenção & controle , Distribuição Aleatória , Timol/administração & dosagem , alfa-Tocoferol/administração & dosagemRESUMO
The aim of this study was to evaluate whether a phytogenic feed additive (PFA) based on essential oils such as carvacrol, thymol and cinnamic aldehyde, could be considered a replacement for antimicrobials used as growth promoters in broiler chickens, as well as to investigate its effect on total bacterial count, biochemical profiles, meat quality and meat fatty acid profile. A total of 240 broiler chicks were randomly distributed into 4 groups with 4 replicates of 15 animals each, as follow: T1 (basal diet only; the control group), T2 (basal diet supplemented with zinc bacitracin), T3 (basal diet with 0.5% of the PFA), T4 (basal diet with 1.0% of the PFA). The addition of 0.5% of the PFA improved live body weight of supplemented birds compared to the control group at 35 and 42 days of age, while the total bacterial count in the environment was reduced when 1.0% of the PFA was used. In addition, intestinal villi height and crypt depth suffered variations during the entire experiment in birds treated with both concentrations of the PFA and zinc bacitracin. Total erythrocyte counts were higher on days 14, 28 and 42 in both treated groups (PFA) compared to the control group, as well as hemoglobin content on days 28 and 42. On the other hand, leukocyte counts were lower on days 14, 28 and 42 due to reduced lymphocyte counts in both PFA treated groups compared to the control group. Serum levels of alanine aminotransferase (ALT) were lower in broilers fed with either concentration of PFA on day 14 of life, and the same was observed regarding aspartate aminotransferase (AST) in broiler treated with 0.5% of the PFA. Also, total protein and globulin levels were lower on days 14 and 28 in groups fed with phytogenic compared to the control group. Regarding meat quality, breast meat showed higher red intensity and shear force in groups fed with both concentrations of phytogenic compared to the control group, while weight loss by cooking was lower. Finally, 1.0% of phytogenic showed lower docosadienoic acid (C22:2) content in breast meat. In conclusion, results showed that the use of PFAs based on carvacrol and thymol may be considered an interesting alternative to increase broilers performance, replacing the use of antimicrobials as growth promoters, as well as an interesting alternative to reduce the total bacterial count in the environment of broiler chickens. Moreover, the diet containing phytogenic also showed hepaprotective effects but deserves attention regarding possible alterations on the immune response.
Assuntos
Acroleína/análogos & derivados , Anti-Infecciosos/administração & dosagem , Bactérias/isolamento & purificação , Peso Corporal , Aditivos Alimentares/administração & dosagem , Monoterpenos/administração & dosagem , Timol/administração & dosagem , Acroleína/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bactérias/classificação , Carga Bacteriana , Análise Química do Sangue , Galinhas , Cimenos , Microbiologia AmbientalRESUMO
Wound healing involves the integration of biological and molecular events and, in case of chronic wounds, the use of drugs can be associated to side effects. Therefore, there is a search for alternatives therapeutics that encompass minimal toxicity. The use of natural compounds is an attractive approach for treating inflammatory disorders, wounds and burns. In this context, thymol has antimicrobial, antioxidant and antiseptic properties and is a promising compound in wound healing and inflammation management. However, essential oils and their constituents such as thymol present high volatility and can also easily decompose, thereby the encapsulation of these compounds into nanoparticles may be an efficient approach to modulate the release of the active ingredient, to increase the physical stability and to eventually reduce the toxicity. The aims of this work were to encapsulate thymol in nanostructured lipid carriers (NLCs) composed of natural lipids and assess its in vivo anti-inflammatory and antipsoriatic activity. The carrier containing thymol was produced by sonication method and showed 107.7 (±3.8) nm of size, zeta potential of -11.6 (±2.9) mV and entrapment efficiency of 89.1 (±4.2)%. Thymol-NLCs were incorporated into a gel and the final formulation presented rheological characteristics and pH suitable for topic application. In addition, the gel containing thymol-NLCs was tested in vivo on two different mouse models of skin inflammation, showing anti-inflammatory activity. Finally, this formulation was tested in an imiquimod-induced psoriasis mouse model and showed improved healing, compared to negative control. Therefore, thymol-NLCs is an interesting formulation for future treatment of inflammatory skin diseases.
Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Lipídeos/química , Nanopartículas/química , Timol/administração & dosagem , Timol/uso terapêutico , Administração Tópica , Aminoquinolinas/efeitos adversos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Betametasona/administração & dosagem , Betametasona/farmacologia , Betametasona/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Composição de Medicamentos , Liberação Controlada de Fármacos , Orelha/patologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Humanos , Imiquimode , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Permeabilidade , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Reologia , Pele/efeitos dos fármacos , Sus scrofa , Timol/farmacologiaRESUMO
The aim of this study was to identify the composition of the essential oil from leaves of Lippia sidoides (EOLS), a typical shrub commonly found in the dry northeast of Brazil, popularly known as "alecrim-pimenta". Additionally, we investigated the nymphicidal, ovicidal, phagoinhibitory and excretion effects of EOLS, its major constituent thymol and its isomer carvacrol, on fourth instar nymphs and eggs of Rhodnius prolixus, the Chagas' disease vector. The nymphicidal and ovicidal activity of thymol, carvacrol, and EOLS was assessed by tests using impregnated Petri dishes. The lethal concentration values (LC50) for EOLS, carvacrol, and thymol were 54.48, 32.98, and 9.38 mg/cm2, respectively. The ovicidal test showed that both carvacrol and thymol (50 mg/cm2) inhibited hatching (50% and 23.3%, respectively), while treatments with 10 mg/cm2 or 50 mg/cm2 EOLS did not affect the hatching rate at all (80% and 90%, respectively). We observed an anti-feeding effect in insects fed with blood containing natural products at the higher concentrations (100 µg/mL). Finally, excretion rate was affected by EOLS and carvacrol, but not by thymol. These findings offer novel insights into basic physiological processes that make the tested natural compounds interesting candidates for new types of insecticides.
Assuntos
Lippia/química , Monoterpenos/administração & dosagem , Óleos Voláteis/administração & dosagem , Rhodnius/efeitos dos fármacos , Timol/administração & dosagem , Animais , Doença de Chagas/transmissão , Cimenos , Relação Dose-Resposta a Droga , Dose Letal MedianaRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). METHODS: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. RESULTS: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1ß, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (p < 0.05). CONCLUSION: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.
Assuntos
Enfisema/tratamento farmacológico , Interleucinas/metabolismo , Lippia/química , Monoterpenos/administração & dosagem , Elastase Pancreática/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Cimenos , Modelos Animais de Doenças , Enfisema/induzido quimicamente , Enfisema/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Camundongos , Monoterpenos/química , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óleos Voláteis/química , Folhas de Planta/química , Timol/administração & dosagem , Timol/química , Timol/isolamento & purificação , Timol/farmacologiaRESUMO
Thymol, a monoterpene phenol derivative of cymene, is found in abundance in the essential oils of Thymus, Origanum, and Lippia species. The present study investigated the gastroprotective actions of thymol (10, 30, and 100 mg/kg, p.o.) in the acute (ethanol- and nonsteroidal anti-inflammatory drug-induced ulcers) and chronic (acetic acid-induced ulcers) ulcer models in rats. Some of the mechanisms underlying to the gastroprotective effect of thymol were investigated in the ethanol-induced ulcer model. Gastric secretion parameters (volume, pH, and total acidity) were also evaluated by the pylorus ligature model, and the mucus in the gastric content was determined. The anti-Helicobacter pylori activity of thymol was performed using the agar-well diffusion method. Thymol (10, 30, and 100 mg/kg) produced dose dependent reduction (P < 0.01) on the total lesion area in the ethanol-induced ulcer model. The gastroprotective response caused by thymol (30 mg/kg) was significantly attenuated (P < 0.001) by intraperitoneal treatment of rats with indomethacin (a non-selective inhibitor of cyclo-oxygenase, 10 mg/kg) and glibenclamide (ATP-sensitive K(+) channel blocker, 10 mg/kg), but not by DL-Propargylglycine (PAG, a cystathionine-γ-lyase inhibitor, 25 mg/kg) and Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME, a non-selective inhibitor of nitric oxide synthase, 70 mg/kg). Thymol (30 and 100 mg/kg) also reduced the ulcer index (P < 0.05) and the total lesion area (P < 0.001) in the indomethacin- and acetic-acid-induced ulcer models, respectively. In the model pylorus ligature, the treatment with thymol failed to significantly change the gastric secretion parameters. However, after treatment with thymol (30 and 100 mg/kg), there was a significant increase (P < 0.01) in mucus production. Thymol no showed anti-H. pylori activity in vitro. Collectively, the present results provide convincing evidence that thymol displays gastroprotective actions on the acute and chronic ulcer models through mechanisms that involve increased in the amount of mucus, prostaglandins, and ATP-sensitive K(+) channels.
Assuntos
Mucinas Gástricas/metabolismo , Canais KATP/metabolismo , Muco/metabolismo , Prostaglandinas/metabolismo , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Timol/farmacologia , Ácido Acético , Doença Aguda , Animais , Doença Crônica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol , Feminino , Helicobacter pylori/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Relação Estrutura-Atividade , Timol/administração & dosagemRESUMO
ABSTRACT Objective The purpose of this randomized, cross-over, in situ study was to determine the remineralization of demineralized dentin specimens after the application of a 10% fluoride (F-) or a 1% chlorhexidine–1% thymol (CHX–thymol) varnish. Material and Methods Twelve individuals without current caries activity wore removable appliances in the lower jaw for a period of four weeks. Each appliance contained four human demineralized dentin specimens fixed on the buccal aspects. The dentin specimens were obtained from the cervical regions of extracted human third molars. After demineralization, half the surface of each specimen was covered with a nail varnish to serve as the reference surface. The dentin specimens were randomly assigned to one of the three groups: F-, CHX–thymol, and control (no treatment). Before the first treatment period and between the others, there were washout periods of one week. After each treatment phase, the changes in mineral content (vol% µm) and the lesion depths (µm) of the dentin slabs were determined by transverse microradiography (TMR). Data analysis was accomplished by the Kruskal-Wallis test and the Mann-Whitney U test (p<0.05). Results The medians (25th/75th percentile) of integrated mineral loss were 312.70 (203.0-628.7) for chlorhexidine varnish, 309.5 (109.8-665.8) for fluoride varnish, and -346.9 (-128.7 - -596.0) for the control group. The medians (25th/75th percentile) of lesion depth were 13.6 (5.7-34.5) for chlorhexidine varnish, 16.5 (5.6-38.1) for fluoride varnish, and -14.2 (-4.5- -32.9) for the control group. Use of the 10% F- or 1% CHX–1% thymol varnishes resulted in significantly decreased mineral loss and lesion depth in dentin when compared with the control group. There were no statistically significant differences among the test groups. Conclusions Within the limitations of this study, the results suggest that the effect of the treatment of demineralized dentin with 10% F- or 1% CHX–1% thymol is better than without any treatment.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Cariostáticos/administração & dosagem , Clorexidina/administração & dosagem , Dentina/efeitos dos fármacos , Fluoretos Tópicos/administração & dosagem , Timol/administração & dosagem , Desmineralização do Dente/tratamento farmacológico , Remineralização Dentária/métodos , Combinação de Medicamentos , Microrradiografia , Valores de Referência , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
Human alveolar echinococcosis (AE) is caused by the fox tapeworm Echinococcus multilocularis and is usually lethal if left untreated. The current strategy for treating human AE is surgical resection of the parasite mass complemented by chemotherapy with benzimidazole compounds. However, reliable chemotherapeutic alternatives have not yet been developed stimulating the research of new treatment strategies such as the use of medicinal plants. The aim of the current study was to investigate the efficacy of the combination albendazole (ABZ)+thymol on mice infected with E. multilocularis metacestodes. For this purpose, mice infected with parasite material were treated daily for 20 days with ABZ (5 mg/kg), thymol (40 mg/kg) or ABZ (5 mg/kg)+thymol (40 mg/kg) or left untreated as controls. After mice were euthanized, cysts were removed from the peritoneal cavity and the treatment efficacy was evaluated by the mean cysts weight, viability of protoscoleces and ultrastructural changes of cysts and protoscoleces. The application of thymol or the combination of ABZ+thymol resulted in a significant reduction of the cysts weight compared to untreated mice. We also found that although ABZ and thymol had a scolicidal effect, the combination of the two compounds had a considerably stronger effect showing a reduction in the protoscoleces viability of 62%. These results were also corroborated by optical microscopy, SEM and TEM. Protoscoleces recovered from ABZ or thymol treated mice showed alterations as contraction of the soma region, rostellar disorganization and presence of blebs in the tegument. However both drugs when combined lead to a total loss of the typical morphology of protoscoleces. All cysts removed from control mice appeared intact and no change in ultrastructure was detected. In contrast, cysts developed in mice treated with ABZ revealed changes in the germinal layer as reduction in cell number, while the treatment with thymol or the ABZ+thymol combination predominantly showed presence of cell debris. On the other hand, no differences were found in alkaline phosphatase (AP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities between control and treated mice, indicating the lack of toxicity of the different drug treatments during the experiment. Because combined ABZ+thymol treatment exhibited higher treatment efficiency compared with the drugs applied separately against murine experimental alveolar echinococcosis, we propose it would be a useful option for the treatment of human AE.
Assuntos
Albendazol/uso terapêutico , Equinococose/tratamento farmacológico , Echinococcus multilocularis , Timol/uso terapêutico , Albendazol/administração & dosagem , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Quimioterapia Combinada , Equinococose/patologia , Echinococcus multilocularis/ultraestrutura , Feminino , Camundongos , Timol/administração & dosagemRESUMO
Objective The purpose of this randomized, cross-over, in situ study was to determine the remineralization of demineralized dentin specimens after the application of a 10% fluoride (F-) or a 1% chlorhexidine-1% thymol (CHX-thymol) varnish. Material and Methods Twelve individuals without current caries activity wore removable appliances in the lower jaw for a period of four weeks. Each appliance contained four human demineralized dentin specimens fixed on the buccal aspects. The dentin specimens were obtained from the cervical regions of extracted human third molars. After demineralization, half the surface of each specimen was covered with a nail varnish to serve as the reference surface. The dentin specimens were randomly assigned to one of the three groups: F-, CHX-thymol, and control (no treatment). Before the first treatment period and between the others, there were washout periods of one week. After each treatment phase, the changes in mineral content (vol% µm) and the lesion depths (µm) of the dentin slabs were determined by transverse microradiography (TMR). Data analysis was accomplished by the Kruskal-Wallis test and the Mann-Whitney U test (p<0.05). Results The medians (25th/75th percentile) of integrated mineral loss were 312.70 (203.0-628.7) for chlorhexidine varnish, 309.5 (109.8-665.8) for fluoride varnish, and -346.9 (-128.7 - -596.0) for the control group. The medians (25th/75th percentile) of lesion depth were 13.6 (5.7-34.5) for chlorhexidine varnish, 16.5 (5.6-38.1) for fluoride varnish, and -14.2 (-4.5- -32.9) for the control group. Use of the 10% F- or 1% CHX-1% thymol varnishes resulted in significantly decreased mineral loss and lesion depth in dentin when compared with the control group. There were no statistically significant differences among the test groups. Conclusions Within the limitations of this study, the results suggest that the effect of the treatment of demineralized dentin with 10% F- or 1% CHX-1% thymol is better than without any treatment.
Assuntos
Cariostáticos/administração & dosagem , Clorexidina/administração & dosagem , Dentina/efeitos dos fármacos , Fluoretos Tópicos/administração & dosagem , Timol/administração & dosagem , Desmineralização do Dente/tratamento farmacológico , Remineralização Dentária/métodos , Adulto , Combinação de Medicamentos , Feminino , Humanos , Masculino , Microrradiografia , Valores de Referência , Estatísticas não Paramétricas , Propriedades de Superfície/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Background: The deterioration of food products, especially of those derived from meat, by pathogenic microorganisms is a major problem in industries. Escherichia coli is a facultative anaerobic bacteria of intestinal origin, and is a cause of concern in the meat industry. The use of essential oils as inhibitors of growth of spoilage and pathogenic microorganisms is a good choice for replacement of chemical additives in foods. This study was aimed at evaluating the in vitro activity of the essential oil of thyme (Thymus vulgaris) and thymol, against E. coli strains, by using a microdilution methodology based on the M31-A3 technique.Materials, Methods & Results: In this study the antimicrobial activities of the essential oil of Thymus vulgaris (thyme) and of the thymol compound were evaluated against 20 E. coli strains obtained from poultry and pigs. The strains are part of the collection of bacteria of the Laboratório de Pesquisas Micológicas of the Universidade Federal de Santa Maria (UFSM). The essential oil of thyme and its constituent, thymol, were commercially acquired (Sigma-Aldrich). Gas chromatography mass spectrometry (GC/MS) was realized on a Agilent chromatograph Model HP 6890 series CG, equipped with a mass selective detector 5973 with electron impact (CG-MS-EI) and identified p-cymene (23.71%), thymol (13.86%) and -terpinene (8.55%) as the major substances...
Assuntos
Anti-Infecciosos/administração & dosagem , Escherichia coli/efeitos dos fármacos , Thymus (Planta)/química , Timol/administração & dosagem , Óleos Voláteis , Conservação de Alimentos/métodos , Qualidade dos AlimentosRESUMO
Background: The deterioration of food products, especially of those derived from meat, by pathogenic microorganisms is a major problem in industries. Escherichia coli is a facultative anaerobic bacteria of intestinal origin, and is a cause of concern in the meat industry. The use of essential oils as inhibitors of growth of spoilage and pathogenic microorganisms is a good choice for replacement of chemical additives in foods. This study was aimed at evaluating the in vitro activity of the essential oil of thyme (Thymus vulgaris) and thymol, against E. coli strains, by using a microdilution methodology based on the M31-A3 technique.Materials, Methods & Results: In this study the antimicrobial activities of the essential oil of Thymus vulgaris (thyme) and of the thymol compound were evaluated against 20 E. coli strains obtained from poultry and pigs. The strains are part of the collection of bacteria of the Laboratório de Pesquisas Micológicas of the Universidade Federal de Santa Maria (UFSM). The essential oil of thyme and its constituent, thymol, were commercially acquired (Sigma-Aldrich). Gas chromatography mass spectrometry (GC/MS) was realized on a Agilent chromatograph Model HP 6890 series CG, equipped with a mass selective detector 5973 with electron impact (CG-MS-EI) and identified p-cymene (23.71%), thymol (13.86%) and -terpinene (8.55%) as the major substances...(AU)
Assuntos
Óleos Voláteis , Thymus (Planta)/química , Timol/administração & dosagem , Escherichia coli/efeitos dos fármacos , Anti-Infecciosos/administração & dosagem , Conservação de Alimentos/métodos , Qualidade dos AlimentosRESUMO
The larval (metacestode) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a mainly hepatic disease characterized by continuous asexual proliferation of metacestodes by exogenous budding, resulting in the tumor-like, infiltrative growth of the parasite lesion. Current chemotherapeutical treatment of AE relies on the use of benzimidazoles, albendazole (ABZ) and mebendazole, but these drugs act parasitostatic rather than parasitocidal, and due to their low success rate they imply a lifelong application causing severe side effects. Thymol is one of the major components of the essential oils of Thymus and is a widely known anti-microbial agent. The aim of the present work was to compare the efficacy of albendazole (ABZ) and thymol separately or combined on E. multilocularis protoscoleces and metacestodes. For this purpose, microscopical examinations at different time points were carried out. Moreover the tegumentary enzyme gamma glutamyl transferase (GGT) was measured to quantify the damage in metacestodes. Even though treatments of in vitro cultured E. multilocularis protoscoleces or metacestodes with ABZ or/and thymol showed that the drugs have an adverse effect on parasite viability, the combination of the two compounds at the concentration of 10µg/ml showed the maximum anti-parasitic effect. Three days postincubation the first effects of the treatment were detected on protoscoleces and a marked reduction in viability (33%) was registered at day 18. Incubation of E. multilocularis metacestodes in the presence of ABZ 10µg/ml+thymol 10µg/ml during 10 days resulted in dramatic alterations such as strongly irregular and fissured surface and markedly disrupted vesicles. Scanning electron microscopy showed that protoscoleces as well as the germinal layer of E. multilocularis metacestodes were dramatically damaged following ABZ or/and thymol treatment. Also an important increase of tegumentary enzyme GGT was registered after 72h postincubation with both drugs. The data reported in this article demonstrate a clear in vitro effect of ABZ+thymol against E. multilocularis protoscoleces and metacestodes.
Assuntos
Albendazol/farmacologia , Anti-Helmínticos/farmacologia , Echinococcus multilocularis/efeitos dos fármacos , Timol/farmacologia , Albendazol/administração & dosagem , Animais , Anti-Helmínticos/administração & dosagem , Quimioterapia Combinada , Equinococose , Equinococose Hepática/tratamento farmacológico , Larva/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos , Timol/administração & dosagemRESUMO
BACKGROUND: In an ongoing project to evaluate essential oils as modulators of antibiotic resistance, the essential oil from Origanum vulgare L. (OVEO), as well as its individual constituents carvacrol (CAR) and thymol (THY), were investigated using Staphylococcus aureus strains possessing efflux mechanisms of resistance to norfloxacin, erythromycin and tetracycline. METHODS: The minimum inhibitory concentration (MIC) values of the antibiotics were determined by agar dilution method, in the absence and in the presence of subinhibitory concentrations of OVEO, CAR or THY. RESULTS: Along with relevant antistaphylococcal activity, OVEO, CAR and THY modulated the activity of tetracycline, i.e. in combination with antibiotics a reduction in the MIC was observed (up to fourfold). CONCLUSIONS: The results presented here represent, as far as we know, the first report of OVEO, CAR and THY as putative efflux pump inhibitors. Broadly, these findings indicate that essential oils could serve as potential sources of compounds capable of modulating drug resistance.