ABSTRACT
Introduction: One of the most frequent problems found in medicinal plants is the absence of clinical, toxicological, and pharmacological studies. Valeriana pavonii is one of the species used in Colombia as an anxiolytic. Further study of this specie is rendered to add information in the toxicological area. Objective: The acute and subchronic oral toxicity of V. pavonii ethanolic extract was evaluated in Wistar rats of both sexes. Materials and methods: The rats were distributed into four groups: the control group received the vehicle (0.5 mL/100 g of corporal weight) and the other three groups received increasing levels of the dosage for 90 days to evaluate characteristics like physical exam, laboratory test (blood chemistry and haematology), and anatomopathological findings. Results: This study reveals that there were no signs of toxicity, mortality, or significant alterations attributable to the ethanolic extract of V. pavonii. Conclusions: The Not Observed Adverse Effect Levels (NOAEL) of V. pavonii ethanolic extract were 2000 and 1000 mg/kg of body weight for the acute and subchronic toxicity studies, respectively.
Introducción: Uno de los problemas más frecuentes asociados con el uso de plantas medicinales es la ausencia de evidencias farmacológicas, toxicológicas y clínicas. Valeriana pavonii es una de las especies más utilizadas popularmente en Colombia con fines ansiolíticos. Es necesario avanzar en el estudio de esta especie para aportar información en el campo toxicológico. Objetivos: Evaluar la toxicidad oral aguda y sub-crónica del extracto etanólico de V. pavonii en ratas Wistar de ambos sexos. Materiales y métodos: En cada uno de los estudios se distribuyeron ratas en cuatro grupos; un grupo control que recibió únicamente vehículo (0.5 ml/100 g de peso corporal) y tres grupos correspondientes a niveles crecientes de dosis, así: para el estudio de toxicidad aguda se administraron en dosis única 20, 200 y 2000 mg/kg con un período de observación de 14 días y para el de toxicidad sub-crónica, dosis diarias de 250, 500 y 1000 mg/kg durante 90 días. Se evaluaron los parámetros de examen físico, los exámenes de laboratorio (química sanguínea y hematología) y el estudio anatomopatológico. Resultados: No se presentaron signos de toxicidad, letalidad ni alteraciones significativas atribuibles al consumo del extracto etanólico de V. pavonii, según el examen físico, el examen anatomopatológico y el análisis de las pruebas de química sanguínea y hematología. Conclusiones: Los valores de nivel sin efectos adversos observados (NOAEL) del extracto etanólico de V. pavonii, fueron 2000 y 1000 mg/kg de peso corporal para los estudios de toxicidad aguda y sub-crónica, respectivamente. No se encontraron valores de nivel más bajo de efecto adverso observado (LOAEL).
Subject(s)
Animals , Rats , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/toxicity , Plants, Medicinal/toxicity , Toxicity Tests/classification , Toxicity Tests/statistics & numerical data , Toxicity Tests/methods , Toxicity Tests/veterinary , Valerian , Valerian/toxicity , Ethanol/pharmacology , Ethanol/toxicityABSTRACT
Prenatal alprazolam (APZ) treatment in 0.1 and 0.2 mg/kg/day doses during 13-20 days of gestation induced significant increase in open-field ambulation, rearings, self-grooming and faecal pellets in rat offspring. Prenatal APZ treated rats displayed significantly increased anxiogenic behaviour on elevated plus maze (spent less time on open arms, more time on enclosed arms and made less number of entries on open arms) and increased anxiogenecity on elevated zero maz e(APZ treated rats spent less time on open arms and made less number of head dips and stretched attend postures in comparison to control rat offspring). The results indicate persistent behavioural alterations in the rat offspring after prenatal exposure to APZ.
Subject(s)
Alprazolam/toxicity , Animals , Anti-Anxiety Agents/toxicity , Anxiety Disorders/chemically induced , Behavior, Animal/drug effects , Exploratory Behavior , Female , Light , Maternal-Fetal Exchange , Maze Learning , Pregnancy , Prenatal Exposure Delayed Effects , RatsABSTRACT
The in utero exposure of hamsters to low doses of diazepam results in impaired host defense against Mycobacterium bovis during adulthood. Delayed developmental immunotoxicity, however, represents a specific situation that might not be general. The present experiment was undertaken to investigate the effects of diazepam on hamster resistance to M. bovis using adult animals. The effects of diazepam treatment on serum cortisol levels were also studied. Adult hamsters (N = 10 for each group) were treated with diazepam (E1 = 1.0, E2 = 2.0 or E3 = 3.0 mg kg-1 day-1 subcutaneously) or with control solution (C) for 30 days. Seven days after the beginning of the treatment, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with the higher (2.0 and 3.0 mg kg-1 day-1) doses of diazepam exhibited: 1) increased granuloma areas in the liver (C = 1.81 + or - 1.39, E2 = 10.29 + or - 4.64 and E3 = 15.80 + or - 4.82) and lung (C = 0.54 + or - 0.55, E2 = 6.28 + or - 3.85 and E3 = 6.31 + + or - 3.56) and 2) increased scores of M. bovis colony-forming units isolated from liver (C = 2.0, E2 = 3.0 and E3 = 3.5), lung (C = 1.0, E2 = 3.0 and E3 = 3.5) and spleen (C = 1.0, E2 = 2.5 and E3 = 4.0). These effects were dose dependent, and were not detected or were less severe in animals treated with the lowest (1.0 mg/kg) dose of diazepam as well as in those of the control group. Furthermore, diazepam treatment (3.0 mg kg-1 day-1 for 30 days) increased (E3 = 71.32 + or - 2.99; N = 10) the serum levels of cortisol compared to control hamsters (C = 22.61 + or - 2.75; N = 10). The present data, that demonstrate an impaired defense against M. bovis in adult hamsters treated with diazepam, were tentatively explained on the basis of a direct and/or indirect action of diazepam on the cytokine network. The effects may be related to stimulation of peripheral benzodiazepine receptor binding sites (PBR) by macrophages and/or lymphocytes, or they may be mediated by PBR stimulation of the adrenals
Subject(s)
Animals , Male , Anti-Anxiety Agents/toxicity , Cricetinae/microbiology , Diazepam/toxicity , Drug Resistance, Microbial , Mycobacterium bovis/drug effects , Tuberculosis/drug therapy , Analysis of Variance , Anti-Anxiety Agents/therapeutic use , Diazepam/therapeutic use , Macrophages/drug effectsABSTRACT
A moderna Psicofarmacoterapia teve início na década de 1960 e revolucionou o tratamento das doenças mentais. De modo sucessivo e, principalmente no início, empírico, antidepressivos como o diazepam, além do lítio e da carbamazepina foram sendo lançados. Muitas dessas drogas, como os antidepressivos tricíclicos, provocam, mesmo em doses terapêuticas, importantes açöes cardiológicas; eles também interagem, farmacoldinâmica ou farmacocineticamente, com medicamentos usados em Cardiologia. Neste artigo, säo abordados os principais efeitos cardiológicos diretos ou indiretos dos psicofármacos usados na terapêutica psiquiátrica.
Subject(s)
Humans , Antipsychotic Agents/adverse effects , Antipsychotic Agents/toxicity , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Heart , Lithium/administration & dosage , Lithium/adverse effects , Lithium/toxicity , Psychotropic Drugs/administration & dosage , Psychotropic Drugs/pharmacology , Anti-Anxiety Agents/toxicity , Carbamazepine , Hypnotics and SedativesABSTRACT
Hyperphagia was induced in mice by p.o. administration of different types of CNS depressant drugs, like chlordiazepoxide 25 mg/kg diazepam 2.5 mg/kg, cyproheptadine 2 mg/kg and phenobarbitone 25 mg/kg. Such hyperphagia was abolished by pretreatment with naloxone 0.1 mg/kg sc. Naloxone per se at this dose produced no significant effect on the food intake. This is suggestive of the role of peptidergic mechanisms in the feeding behaviour in mice.
Subject(s)
Animals , Anti-Anxiety Agents/toxicity , Central Nervous System Depressants/administration & dosage , Chlordiazepoxide/administration & dosage , Cyproheptadine/administration & dosage , Diazepam/administration & dosage , Eating/drug effects , Feeding Behavior/drug effects , Female , Histamine Antagonists/toxicity , Hypnotics and Sedatives/toxicity , Male , Mice , Naloxone/administration & dosage , Phenobarbital/administration & dosage , beta-Endorphin/physiologyABSTRACT
Neste artigo, apresentamos o conceito de segurança e tolerância dos benzodiazepínicos. Baseados nesta definiçäo, proporemos uma nova classificaçäo para as situaçöes comportamentais induzidas pelos benzodiazepínicos. Por fim, empreendemos uma revisäo crítica dos casos de segurança e tolerância dos benzodiazepínicos descritos na literatura especializada