RESUMEN
N-Nitrosamines (also referred to as nitrosamines) are a class of substances, many of which are highly potent mutagenic agents which have been classified as probable human carcinogens. Nitrosamine impurities have been a concern within the pharmaceutical industry and by regulatory authorities worldwide since June 2018, when regulators were informed of the presence of N-nitrosodimethylamine (NDMA) in the angiotensin-II receptor blocker (ARB) medicine, valsartan. Since that time, regulatory authorities have collaborated to share information and knowledge on issues related to nitrosamines with a goal of promoting convergence on technical issues and reducing and mitigating patient exposure to harmful nitrosamine impurities in human drug products. This paper shares current scientific information from a quality perspective on risk factors and potential root causes for nitrosamine impurities, as well as recommendations for risk mitigation and control strategies.
Asunto(s)
Nitrosaminas , Humanos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Factores de Riesgo , Preparaciones FarmacéuticasRESUMEN
Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.
Asunto(s)
Industria Farmacéutica/legislación & jurisprudencia , Control de Medicamentos y Narcóticos/legislación & jurisprudencia , Medicamentos Genéricos/farmacología , Brasil , MercadotecníaRESUMEN
Schizophrenia was proposed as a progressive neurodevelopmental disorder. In this regard herein we attempted to determine progressive inflammatory and oxidative alterations induced by a neonatal immune challenge and its possible reversal by clozapine administration. For this end, Wistar rats at postnatal day (PN) 5-7 were administered the viral mimetic polyriboinosinic-polyribocytidilic acid (polyI:C) or saline. A distinct group of animals additionally received the antipsychotic drug clozapine (25mg/kg) from PN60 to 74. At PN35 (periadolescence), 60 (adult) and 74 (adulthood) the animals were submitted to behavioral determinations of prepulse inhibition of the startle (PPI) and Y maze task for working memory evaluation. At PN35 and 74 the animals were sacrificed and the hippocampus (HC), prefrontal cortex (PFC) and striatum (ST) immunostained for Iba-1, a microglial marker, and inducible nitric oxide synthase (iNOS). At PN74 oxidative stress parameters, such as, reduced glutathione levels (GSH) and lipid peroxidation were determined. The results showed a progressive increase of microglial activation and iNOS immunostaining from PN35 to PN74 mainly in the CA2 and CA3 regions of the HC and in the ST. At PN74 neonatal challenge also induced an oxidative imbalance. These inflammatory alterations were accompanied by deficits in PPI and working memory only in adult life that were reversed by clozapine. Clozapine administration reversed microglial activation and iNOS increase, but not the alterations of oxidative stress parameters. Taken together these results give further evidences for a neuroprogressive etiology and course of schizophrenia and that clozapine may partly alleviate this process.
Asunto(s)
Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Discapacidades del Desarrollo/tratamiento farmacológico , Discapacidades del Desarrollo/etiología , Microglía/patología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Esquizofrenia/complicaciones , Factores de Edad , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Microglía/metabolismo , Estrés Oxidativo/efectos de los fármacos , Poli I-C/farmacología , Ratas , Ratas Wistar , Reflejo de Sobresalto/efectos de los fármacos , Esquizofrenia/inducido químicamenteRESUMEN
PURPOSE: Our great interest in this work was study the synergism between l-tryptophan and dipyrone or paracetamol as well as the interaction of kynurenic acid (l-tryptophan metabolite) and these analgesics agents utilizing a robust methodology. METHODS: We performed the writhing test induced by acetic acid in mice to evaluate the antinociceptive effect of the treatments isolated and combined (p.o. and i.p.). Dose-response curves were constructed and the values of ED50 for treatment alone and combined were statistically compared. In addition, isobolographic analysis was performed and the experimental values were compared with the theoretical values for simple additive effect. RESULTS: The combined treatment with l-tryptophan and dipyrone or paracetamol reduced significantly the ED50 of these analgesics when compared to the isolated treatments. l-tryptophan alone has no antinociceptive effect. l-Tryptophan increases the central amount of 5-HT and the synergism with dipyrone is antagonized by the 5-HT depletion. The kyna has an antinociceptive dose-related effect and a synergistic interaction with dipyrone and paracetamol verified by isobolographic analyses and confirmed by experimental values of ED50 of combined treatments were statistically lower than theoretical calculated values for simple additive effect. Melatonin antagonist receptor attenuates the antinociceptive synergism between l-tryptophan and dipyrone. CONCLUSION: Our results demonstrate that the increased 5-HT amount on the central nervous system is not per se capable to induce antinociception. The l-tryptophan interacts synergistically with dipyrone and paracetamol both orally and by i.p. route. This effect is dependent on the biotransformation of l-tryptophan to 5-HT and involves kynurenic acid and melatonin receptors.
Asunto(s)
Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Dipirona/administración & dosificación , Ácido Quinurénico/administración & dosificación , Triptófano/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Ratones , Dimensión del Dolor/métodos , Receptores de Melatonina/antagonistas & inhibidores , Triptaminas/administración & dosificaciónRESUMEN
Riparin II (RipII), an alkamide isolated from the green fruit of Aniba riparia, was tested in the various animal models of inflammation to investigate its anti-inflammatory activity. Male Wistar rats (180-240g) were treated with RipII by gavage at doses 25 or 50mg/kg, before initiating the inflammatory responses. The tests used were paw edema induced by carrageenan, dextran, histamine or serotonin; peritonitis induced by carrageenan and fMLP, as well as the measurement of MPO activity, TNF-α and Il-1ß amount in the peritoneal fluid. In the animal models of carrageenan and dextran-induced paw edema, the animals treated with RipII showed lower edema than those of the control group. Treatment with RipII also reduced the paw edema induced by histamine but not serotonin. In the carrageenan-induced peritonitis model, treatment with RipII reduced leukocyte migration, the MPO activity and the amount of TNF-α and IL-1ß in the peritoneal fluid. In summary, these results indicate that RipII has an anti-inflammatory activity in chemical models of acute inflammation. RipII might be directly or indirectly inhibiting the activity, production or release of pro-inflammatory mediators involved in the generation of the pain associated with inflammation.
Asunto(s)
Antiinflamatorios/farmacología , Benzamidas/farmacología , Inflamación/tratamiento farmacológico , Tiramina/análogos & derivados , Animales , Modelos Animales de Enfermedad , Edema/inducido químicamente , Edema/tratamiento farmacológico , Inflamación/inducido químicamente , Masculino , Malondialdehído/metabolismo , Ratones , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Tiramina/farmacologíaRESUMEN
BACKGROUND: Citronellyl acetate (CAT), a monoterpene product of the secondary metabolism of plants, has been shown in the literature to possess several different biological activities. However, no antinociceptive abilities have yet been discussed. Here, we used acute pain animal models to describe the antinociceptive action of CAT. METHODS: The acetic acid-induced writhing test and the paw-licking test, in which paw licking was induced by glutamate and formalin, were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC, PKA, TRPV1, TRPA1, TRPM8 and ASIC in its antinociceptive mechanism. To do so, we induced paw-linking using agonists. RESULTS: CAT was administered intragastrically (25, 50, 75, 100 and 200 mg/kg), and the two higher doses caused antinociceptive effects in the acetic acid model; the highest dose reduced pain for 4h after it was administered (200 mg/kg). In the formalin test, two doses of CAT promoted antinociception in both the early and later phases of the test. The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT. Pretreatment with CAT did not alter locomotor activity or motor coordination. In an investigation into the participation of TRP channels and ASICs in CAT's antinociceptive mechanism, we used capsaicin (2.2 µg/paw), cinnamaldehyde (10 mmol/paw), menthol (1.2 mmol/paw) and acidified saline (2% acetic acid, pH 1.98). The results showed that TRPV1, TRPM8 and ASIC, but not TRPA1, are involved in the antinociceptive mechanism. Finally, the involvement of PKC and PKA was also studied, and we showed that both play a role in the antinociceptive mechanism of CAT. CONCLUSION: The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism.
Asunto(s)
Canales Iónicos Sensibles al Ácido/efectos de los fármacos , Dolor Agudo/tratamiento farmacológico , Analgésicos/farmacología , Monoterpenos/farmacología , Dolor Nociceptivo/tratamiento farmacológico , Canales Catiónicos TRPV/efectos de los fármacos , Ácido Acético/toxicidad , Canales Iónicos Sensibles al Ácido/metabolismo , Dolor Agudo/inducido químicamente , Dolor Agudo/metabolismo , Administración Oral , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Extremidades/patología , Formaldehído/toxicidad , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Dolor Nociceptivo/inducido químicamente , Dolor Nociceptivo/metabolismo , Dimensión del Dolor , Prueba de Desempeño de Rotación con Aceleración Constante , Canales Catiónicos TRPV/metabolismoRESUMEN
OBJECTIVES: Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol which is present in the essential oil of oregano and thyme. We have investigated the behavioural effects of carvacrol in animal models of pain, such as acetic acid-induced abdominal constriction, formalin and hot-plate tests in mice. The spontaneous motor activity of animals treated with carvacrol was investigated using open-field and rotarod tests. METHODS: Carvacrol was administered orally, at single doses of 50 and 100 mg/kg while indometacin (5 mg/kg), morphine (7.5 mg/kg) and diazepam (2 mg/kg) were used as standard drugs. Naloxone (1 mg/kg) and l-arginine (150 mg/kg) were used to elucidate the possible antinociceptive mechanism of carvacrol on acetic acid-induced abdominal constriction and formalin tests. KEY FINDINGS: The results showed that carvacrol produced significant inhibitions on nociception in the acetic acid-induced abdominal constriction, formalin and hot-plate tests. In the open-field and rotarod tests carvacrol did not significantly impair the motor performance. The effect of the highest dose of carvacrol in mice in the acetic acid-induced abdominal constriction and formalin tests were not reversed by naloxone or l-arginine. CONCLUSIONS: Based on these results, it has been suggested that carvacrol presents antinociceptive activity that may not act through the opioid system nor through inhibition of the nitric oxide pathway.
Asunto(s)
Analgésicos/uso terapéutico , Monoterpenos/uso terapéutico , Actividad Motora/efectos de los fármacos , Origanum/química , Dolor/tratamiento farmacológico , Fitoterapia , Thymus (Planta)/química , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/etiología , Ácido Acético , Analgésicos/efectos adversos , Analgésicos/farmacología , Animales , Arginina/farmacología , Conducta Animal/efectos de los fármacos , Cimenos , Modelos Animales de Enfermedad , Formaldehído , Calor , Masculino , Ratones , Ratones Endogámicos , Monoterpenos/efectos adversos , Monoterpenos/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Dolor/etiología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
This work examined the gastroprotection of (-)-α-bisabolol, an unsaturated optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants. (-)-α-Bisabolol has been described as a compound capable of reducing the gastric ulcer area in response to absolute ethanol. We evaluated the gastroprotection of (-)-α-bisabolol in ethanol-induced gastric lesions model through histopathological assessment, measurement of the membrane lipids peroxidation (MDA), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity and the nitrite amount. Our results showed that (-)-α-bisabolol was able to reduce injuries associated with the administration of ethanol and the formation of thiobarbituric acid reactive substances (MDA) was also able to increase SOD activity and reduce the influx of cells inflammatory (neutrophils) in the gastric mucosa. The effect of (-)-α-bisabolol seems to be unrelated to the nitric oxide. (-)-α-Bisabolol caused a reduction of catalase activity. These findings show that (-)-α-bisabolol is able to decrease oxidative stress and inflammatory event associated with the lesions induced by ethanol.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Neutrófilos/patología , Sustancias Protectoras/farmacología , Sesquiterpenos/farmacología , Úlcera Gástrica/prevención & control , Superóxido Dismutasa/metabolismo , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Animales , Catalasa/metabolismo , Etanol/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/enzimología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos , Sesquiterpenos Monocíclicos , Neutrófilos/metabolismo , Nitritos/metabolismo , Peroxidasa/metabolismo , Sustancias Protectoras/uso terapéutico , Sesquiterpenos/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
(-)-α-Bisabolol is an unsaturated, optically active sesquiterpene alcohol obtained by the direct distillation of essential oil from plants such as Vanillosmopsis erythropappa and Matricaria chamomilla. (-)-α-Bisabolol has generated considerable economic interest, as it possesses a delicate floral odour and has been shown to have antiseptic and gastroprotective activities. In this study, (-)-α-bisabolol was tested in standardised rodent models by gavage administration at doses of 100 and 200 mg/kg in the models of inflammation and 25 and 50 mg/kg in the models of nociception. In the inflammatory models of paw oedema induced by carrageenan and dextran, the mice treated with (-)-α-bisabolol showed smaller oedemas compared to animals treated only with the vehicle. (-)-α-Bisabolol was capable of reducing paw oedemas induced by 5-HT but not oedemas induced by histamine. (-)-α-Bisabolol demonstrated anti-nociceptive activity in the models of visceral nociception induced by acetic acid and in the second phase of the nociception test induced by the intraplantar administration of formalin. (-)-α-Bisabolol did not have any effect in a thermal nociception model using a hot plate but was able to diminish mechanical inflammatory hypernociception evoked by carrageenan. These findings suggest that the anti-nociceptive action of (-)-α-bisabolol is not linked to a central mechanism but instead is related to the inflammatory process. (-)-α-Bisabolol was able to decrease leukocyte migration, protein extravasations and the amount of TNF-α to the peritoneal cavity in response to carrageenan. Additionally, (-)-α-bisabolol reduced neutrophil degranulation in response to phorbol-myristate-acetate. We demonstrate, for the first time, the peripheral anti-inflammatory and anti-nociceptive activities of (-)-α-bisabolol.
Asunto(s)
Inflamación/tratamiento farmacológico , Dolor/tratamiento farmacológico , Sesquiterpenos/farmacología , Analgésicos/administración & dosificación , Analgésicos/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/fisiopatología , Inflamación/fisiopatología , Masculino , Ratones , Sesquiterpenos Monocíclicos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Dolor/fisiopatología , Ratas , Sesquiterpenos/administración & dosificación , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
O objetivo deste trabalho foi identificar o uso de bebidas alcoólicas pelos estudantes da maior escola pública da cidade de Cajazeiras, PB. Realizou-se estudo descritivo transversal, com abordagem quantitativa, e a amostra ficou composta por 300 alunos de uma escola pública da cidade. Verificou-se que 71 por cento já tinham usado álcool, 66,4 por cento fizeram experimentação da droga entre 13-17 anos, 69,4 por cento usaram por diversão, 59,5 por cento já se embriagaram ao consumir álcool, 21,3 por cento experimentam em bares/boates e 39,4 por cento beberam com maior frequência em bares/danceterias/boates. Constatou-se que há alto consumo de álcool entre adolescentes, sendo necessária a implementação de ações educativas, visando a diminuição do consumo.(AU)
The objective of this study was to identify the use of alcohol among students of the largest public school in Cajazeiras, Pernambuco. This cross-sectional descriptive study was performed with a sample of 300 students. It was found that 71 percent had drunk alcohol before; 66.4 percent had their first drink when they were between 13-17 years old; 69.4 percent drank for fun; 59.5 percent have already gotten drink from consuming alcohol; 21.3 percent had their first drink at bars/night clubs; 39.4 percent usually drank at bars/dance clubs/night clubs. It was found that alcohol use is high among adolescents, thus there is a need to implement educational actions, aiming at reducing alcohol use.(AU)
El objetivo de este trabajo fue identificar el uso de bebidas alcohólicas por parte de estudiantes de la mayor escuela pública de la ciudad de Cajazeiras-PB. Se realizó un estudio descriptivo transversal con abordaje cuantitativo, sobre muestra de 300 alumnos de una escuela pública de la ciudad. Se verificó que 71 por ciento ya había consumido alcohol; 66,4 por ciento experimentó con drogas entre los 13-17 años; 21,3 por ciento tuvieron experiencias en bares/discotecas; 39,4 por ciento bebieron con mayor frecuencia en bares/discobares/discotecas. Se constató que hay alto consumo de alcohol entre adolescentes, haciéndose necesaria la implementación de acciones educativas, apuntando a la disminución del consumo.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Consumo de Bebidas Alcohólicas , Estudiantes , Educación Primaria y SecundariaRESUMEN
O objetivo deste trabalho foi identificar o uso de bebidas alcoólicas pelos estudantes da maior escola pública da cidade de Cajazeiras, PB. Realizou-se estudo descritivo transversal, com abordagem quantitativa, e a amostra ficou composta por 300 alunos de uma escola pública da cidade. Verificou-se que 71 por cento já tinham usado álcool, 66,4 por cento fizeram experimentação da droga entre 13-17 anos, 69,4 por cento usaram por diversão, 59,5 por cento já se embriagaram ao consumir álcool, 21,3 por cento experimentam em bares/boates e 39,4 por cento beberam com maior frequência em bares/danceterias/boates. Constatou-se que há alto consumo de álcool entre adolescentes, sendo necessária a implementação de ações educativas, visando a diminuição do consumo.
The objective of this study was to identify the use of alcohol among students of the largest public school in Cajazeiras, Pernambuco. This cross-sectional descriptive study was performed with a sample of 300 students. It was found that 71 percent had drunk alcohol before; 66.4 percent had their first drink when they were between 13-17 years old; 69.4 percent drank for fun; 59.5 percent have already gotten drink from consuming alcohol; 21.3 percent had their first drink at bars/night clubs; 39.4 percent usually drank at bars/dance clubs/night clubs. It was found that alcohol use is high among adolescents, thus there is a need to implement educational actions, aiming at reducing alcohol use.
El objetivo de este trabajo fue identificar el uso de bebidas alcohólicas por parte de estudiantes de la mayor escuela pública de la ciudad de Cajazeiras-PB. Se realizó un estudio descriptivo transversal con abordaje cuantitativo, sobre muestra de 300 alumnos de una escuela pública de la ciudad. Se verificó que 71 por ciento ya había consumido alcohol; 66,4 por ciento experimentó con drogas entre los 13-17 años; 21,3 por ciento tuvieron experiencias en bares/discotecas; 39,4 por ciento bebieron con mayor frecuencia en bares/discobares/discotecas. Se constató que hay alto consumo de alcohol entre adolescentes, haciéndose necesaria la implementación de acciones educativas, apuntando a la disminución del consumo.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Consumo de Bebidas Alcohólicas , Educación Primaria y Secundaria , EstudiantesRESUMEN
Melatonin, N-acetyl-5-methoxytryptamine, the major hormone produced by the pineal gland under the influence of the dark/light cycle, has been shown to have a large number of therapeutic possibilities. It has been utilized in several countries for circadian rhythm disorders, sleep disturbances, jet lag, and sleep-wake cycle disturbances in blind people, and shift workers. In our mechanism of act, the G(i) protein-coupled metabotropic melatonin receptors MT1 and MT2 are the primary mediators of the physiological actions of melatonin. This hormone plays an important role in the regulation of physiological and neuroendocrine functions, such as synchronization of seasonal reproductive rhythms and entrainment of circadian cycles. In addition to its chronobiological role, several pharmacological effects of melatonin have been reported in mammals including sedative, antioxidant, anxiolytic, antidepressant, anticonvulsant, and analgesic activities. There is some evidence from clinical trials that melatonin can be helpful in that event. Current trends of pharmacological functions of melatonin pointed out its use in the treatment of neurodegenerative and neoplastic diseases. These effects and uses of melatonin are mentioned but further confirmatory studies are needed in most of them.
Asunto(s)
Melatonina/farmacología , Melatonina/uso terapéutico , Trastornos del Sueño del Ritmo Circadiano/tratamiento farmacológico , Animales , Antidepresivos/farmacología , Antioxidantes/metabolismo , Depresión/tratamiento farmacológico , Depuradores de Radicales Libres , Humanos , Indenos , Síndrome Jet Lag/dietoterapia , Melatonina/análogos & derivados , Receptores de Melatonina/metabolismo , Sueño/fisiologíaRESUMEN
This work describes the gastroprotective actions of esculin (6,7-dihydroxycoumarin-6-o-glucoside) against indomethacin- or ethanol-induced lesions and verifies the role of nitric oxide, ATP-dependent K(+) channels, prostaglandins, transient receptor potential vanilloid 1 and antioxidant effects in the gastroprotective mechanism of esculin in the ethanol-induced gastric lesion model. The intragastric administration of esculin at doses of 12.5, 25 and 50 mg/kg was able to protect the gastric mucosa against ethanol (0.2 mL/animal p.o.), and esculin at doses of 25 and 50 mg/kg protected against indomethacin-induced lesions (20mg/kg p.o.). Administration of l-NAME (10mg/kg i.p.), glibenclamide (10mg/kg i.p.) or indomethacin (10mg/kg p.o.), but not capsazepine (5mg/kg p.o.), was able to reduce the gastroprotection promoted by esculin (25mg/kg) on the ethanol-induced lesions. Measurements of nitrite, a NO metabolite, were increased in the group that was pretreated with esculin. In terms of antioxidant activity as a gastroprotective mechanism of esculin, the results show that pre-treatment with esculin decreased the amount of GSH, increased SOD activity, did not interfere with the CAT activity and decreased both the MPO activity and the MDA amount. In conclusion, pre-treatment with esculin confers significant gastroprotective and antioxidant activity and leads to a reduction in gastric injury; the mechanisms underlying these effects include stimulation of endogenous prostaglandins, nitric oxide synthesis, opening of K(ATP) channels and reduction of free radicals or modulation of antioxidant enzyme systems.
Asunto(s)
Esculina/farmacología , Fármacos Gastrointestinales/farmacología , Estómago/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Mucosa Gástrica/metabolismo , Peroxidación de Lípido , Masculino , Ratones , Estómago/enzimología , Estómago/patologíaRESUMEN
The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K(+) channels (K(ATP) channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-L-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, K(ATP) channel opening, and antioxidant properties.