RESUMO
OBJECTIVE: This study was designed to investigate the anti-inflammatory and antipyretic effects of kaurenic acid (KA), a tetracyclic diterpenoid carboxylic acid, using in vivo experimental animal models. MATERIAL AND METHODS: The anti-inflammatory activity of KA was evaluated in rats, using egg albumin-induced paw edema (acute test) and Freund's complete adjuvant-induced paw edema (subacute test), whereas the antipyretic effect was studied in rabbits by peptone-induced pyresis. Acute and subacute toxicity of KA were analyzed in NMRI mice. RESULTS: KA showed anti-inflammatory and antipyretic properties, and the effect caused was significantly dose-related (P < 0.001) in both cases. The mean lethal doses of KA were 439.2 and 344.6 mg/kg for acute and subacute toxicity, respectively. CONCLUSION: On the basis of these findings, it may be inferred that KA has an anti-inflammatory and antipyretic potential.
RESUMO
Existe un cúmulo de evidencias sobre la utilidad de administrar analgésicoas antes de la cirugía (analgesia preventiva) en animales. El objeto de este trabajo fue determinar el efecto de flunixin meglumina (FM) administrado antes de la cirugía sobre los signos de dolor peri-operatorio en perras sometidas a ovario-histerectomía (OVH). Se utilizó la escala de medición de dolor de la Universidad de Melbourne para medir los signos y grado de dolor. Se usaron dos grupos de animales, uno que conformaba el grupo experimental, el cual fue prestratado con FM antes de la cirugía y el grupo control o no tratado. El grupo experimental mostró valores de mediana menores que el grupo control durante el trans-operatorio y post-operatorio inmediato, lo que representa menor grado de dolor en los animales pretratados con FM. En la interpretación del valor total de la escala, se observó que los animales del grupo experimental presentaron dolor leve a moderado y los grupos control, dolor leve a severo. En el grupo control, la frecuencia cardiaca aumentó significativamente durante el trans-operatorio (116.87 ± 29.61 lat/min) y post-operatorio inmediato (133.94 ± 29.82 lat/min) con respecto al pre-operatorio inmediato (98.3±21.0 lat/min); mientras que el grupo experimental no presentó aumentos de la frecuencia cardiaca. Estos resultados sugieren que el uso de FM como analgesia y preventiva en OCH reduce el grado dolor en perras y podría mejorar la analgesia durante el período peri-operatorio.
There are a great number of evidences about the usefulness of analgesic drug administration before the surgery (preventive analgesia) in animals. The aim of this work was to determine the effect of flunixin meglumine (FM) administered before the surgery upon the perioperative signs of pain in bitches that underwent ovariohisterectomy (OVH). The signs and levels of pain were measured using the scale of the University of Melbourne. Two groups were used, the experimental group which was treated with FM and control group. The experimental group showed median values lower than the control group, which indicated less level of pain during the trans-operative period and immediately after surgery. According to total values of the scale, animals in experimental group showed light to moderated levels of pain, whereas light to severe pain levels were found in control. Also in control group, the heart frequency increased during the trans-operative period (116.87 ± 29.61 beat/min) and immediately after surgery (133.94 ± 29.82 beat/min), when they were compared with the pre-operative period (98.3 ± 21.0 beat/min); in contrast, animals in the experimental group did not show heart frequency increment. These results suggest that the use of FM in preventive analgesia during OVH reduces the level of pain in bitches and it may improve the analgesia during the perioperative period.
Assuntos
Animais , Feminino , Cães , Analgesia/métodos , Analgesia/veterinária , Cirurgia Geral/métodos , Dor/veterinária , Histerectomia/métodos , Histerectomia/veterinária , Meglumina/uso terapêutico , Medicina VeterináriaRESUMO
Kaurenic acid [(-)-kaur-16-en-19-oic acid] is a diterpene isolated from the aerial parts of Espeletia semiglobulata, one of 85 species of Espeletiinae found in Venezuela. Its anticonvulsive activity was studied using two different models of experimental seizures: spinal seizures induced by sudden cooling (SSSC) in amphibians and seizures induced by pentylenetetrazol (PTZ) in mice. In SSSC, kaurenic acid (KA) inhibited the tonic hind-limb extension with an ED50 of 2.5 mg/kg. It was 4-fold more potent than known anticonvulsant drugs such as carbamazepine and phenytoin and 100-fold more potent than valproic acid. However, KA as well as valproic acid were ineffective against the clonic phase of SSSC. In the PTZ-induced seizures, KA at doses of 0.625 and 1.25 mg/kg increased the latency of seizure onset and protected against generalized clonic-tonic seizures by 45% and 65%, respectively. The sedative effects of KA had an ED50 of 8.5 mg/kg in mice and 75 mg/kg in amphibians. This work provides experimental evidence supporting the potential value of kaurenic acid as an anticonvulsive drug.
Assuntos
Anticonvulsivantes/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/toxicidade , Bufo marinus , Temperatura Baixa/efeitos adversos , Modelos Animais de Doenças , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Diterpenos/toxicidade , Avaliação Pré-Clínica de Medicamentos , Membro Posterior/inervação , Camundongos , Contração Muscular/efeitos dos fármacos , Debilidade Muscular/induzido quimicamente , Pentilenotetrazol/toxicidade , Reflexo Anormal/efeitos dos fármacos , Convulsões/etiologia , Convulsões/prevenção & controle , Medula Espinal/efeitos dos fármacosRESUMO
El ácido kaurénico [(-)-kaur-16-en-19-oic acid] es un diterpeno aislado de las partes aéreas de la planta Espeletia semiglobulata, una de la 85 especies de Espeletiinae encontradas en Venezuela. El efecto anticonvulsivo del ácido kaurénico fue estudiado empleando dos modelos diferentes de convulsiones experimentales: convulsiones espinales inducidas por enfriamiento brusco (SSSC) en anfibios y convulsiones inducidas por pentilenotetrazol (PTZ) en ratones. En SSSC, el ácido kaurénico (KA) inhibió la fase ténica con una ED50 de 2,5 mg/kg. KA fue cuatro veces más potente que anticonvulsivos conocidos tales como carbamazepina y fenitoína y 100 veces más potente que el ácido valproico. Sin embargo, el KA al igual que el ácido valproico, fueron inefectivos contra la fase clónica de las SSSC. En convulsiones inducidas por PTZ en ratones, el KA aumentó la latencia y disminuyó la incidencia de la fase clónica-tónica generalizada de las convulsiones inducidas por PTZ en 45 por ciento y 65 por ciento, a dosis de 0,62 y 1,25 mg/kg, respectivamente. KA produjo sedación a una dosis efectiva (ED50) de 8,5 mg/kg en los ratones y de 75 mg/kg en anfibios. Este trabajo aporta evidencia experimental que soporta el valor potencial del KA como una droga anticonvulsiva.
Assuntos
Animais , Camundongos , Anticonvulsivantes , Carbamazepina , Diterpenos , Convulsões , Medicina , VenezuelaRESUMO
Although the induction of mild to moderate cerebral hypothermia in mammals can have neuroprotective activity, some deleterious effects have been described when inducing deep hypothermia during cooling of the brain. In the spinal cord, rapid deep cooling can induce seizure activity accompanied by release of the excitatory neurotransmitters, glutamate and aspartate. We used cold-sensitive tropical amphibians as a model to determine (a) the critical temperature inside the central nervous system necessary to induce seizures during rapid cooling; (b) the survival rate during slow deep cooling of the whole animal; and (c) whether deep cooling can cause neuronal cell damage. Seizures induced by deep rapid (
Assuntos
Anfíbios/fisiologia , Encéfalo/fisiologia , Hipotermia Induzida/efeitos adversos , Medula Espinal/fisiologia , Animais , Glicemia/análise , Proteínas Sanguíneas/análise , Temperatura Corporal , Encéfalo/citologia , Bufo marinus , Morte Celular , Eletroencefalografia , Hipotermia Induzida/métodos , Modelos Animais , Neurônios Motores/citologia , Neurônios Motores/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Reaquecimento , Medula Espinal/citologia , Fatores de TempoRESUMO
Although some of the clinical signs associated with epilepsy have their origin in supraspinal structures, it is the spinal cord in the end, which is responsible for generating the typical pattern of tonic-clonic contractions associated with a convulsion. Indeed, the spinal cord isolated from influence of the brain is capable of convulsive and paroxysmal activity that exhibits the same stereotyped motor pattern seen in the intact animal. This motor pattern can be reproduced experimentally by cooling the isolated spinal cord of amphibians. The isolated spinal cord-hindleg preparation of toad was used. Convulsive activity was induced by placing the isolated spinal cord into a Ringer's bath kept at 7 degrees C. The characteristic phases of the convulsion and their intensity were assessed by recording tonic-clonic contractions of hindleg muscles. Two main endpoints were used to assess the anticonvulsive activity of the drugs tested: first, their ability to block only the tonic hind-limb extension (THE) and second, their ability to block all tonic-clonic activity. The ED50 values and its 95% confidence interval estimated for abolition of THE for each drugs was (mg/kg): carbamazepine 8.6 (6.8-10.8), phenytoin 13 (7.1-23.6), diazepam 0.007 (0.004-0.01), MK-801 3.4 (2.0-5.7), valproate 120 (40-400), phenobarbital 17.1 (12.2-23.9), pentobarbital 10 (6-16.4), mephenesin 2-5 and acetazolamide >500. The ability of some of these drugs to inhibit this kind of seizure activity at doses within therapeutic range suggests a potential use of this isolated preparation as a model in the study and testing of new anticonvulsive drugs.
Assuntos
Anticonvulsivantes/uso terapêutico , Temperatura Baixa/efeitos adversos , Convulsões/tratamento farmacológico , Convulsões/etiologia , Medula Espinal , Animais , Anuros , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletromiografia/métodos , Técnicas In Vitro , Medula Espinal/fisiopatologiaRESUMO
Cold acclimatization (4-5ºC) is accompanied by 2-3 fold increase of brown adipose tissue (BAT). This rapid growth of interscapular BAT was studied after histamine depletion. In control rats maintenained at room temperature (28 ñ 2ºC) the BAT histamine content was 23.4 ñ 5.9 (mean ñ SD) µg/g of tissue and cold acclimatization (5 ñ 1ºC) produced a signifacant increase of BAT weight, but reduced the histamine content to 8.4 ñ 1.9 µg/g. The total weight of BAT after 20 days of acclimatization was unaffected by depletion of histamine due to compound 48/80. The low level of histamine in BAT of cold acclimatization rats could be a fast rate of amine utilization; alternatively and altered synthesis or storage process may occur during acclimatization.
Assuntos
Animais , Ratos , Tecido Adiposo Marrom/crescimento & desenvolvimento , Histamina , Mastócitos , p-Metoxi-N-metilfenetilaminaRESUMO
El esfriamiento brusco de la médula espinal aislada de sapos induce una convulsión característica en los miembros posteriores. En este trabajo, el kinurenato (KYN), un antagonista no competitivo de los receptores N-metil-D-aspartato (NMDA) y el 20amino-5-fosfonovalerato (APV), un antagonista competitivo de los receptores NMDA, fueron ensayados en el patrón, la latencia y la duración de esta convulsión espinal. APV, 1,3-2,5 mmol/Kg and KYN, 2,6 mmol/Kg, inhibieron la fase tónica de esta convulsión y prolongaron la duración de la fase clónica después de la administración intralinfática (i.l.). El mismo efecto fue observado después de la inyección intratecal de dosis de 10 ó 20 µmol/20 µl de cada droga. La fase clónica fue maracadamente atenuada por KYN a dosis altas de 5.3 ó 10.6 mmol/Kg, i.l., sugiriendo que receptores del tipo no NMDA podrían tener alguna mediciación en la generación de dicha fase. Ambos antagonistas retardaron el comienzo de las convulsiones, indicando que la activación de los receptores NMDA están probablemente involucrados en el comienzo de este tipo de convulsiones. Este modelo espinal podría ser una técnica útil para el ensayo de otros antagonistas de amino ácidos excitatorios
Assuntos
Animais , 2-Amino-5-fosfonovalerato/farmacologia , Temperatura Baixa , Cinurenina/farmacologia , Contração Muscular/efeitos dos fármacos , Convulsões/etiologia , Medula Espinal/fisiologia , 2-Amino-5-fosfonovalerato/uso terapêutico , Bufo marinus , Ácido Cinurênico/uso terapêutico , Convulsões/prevenção & controleRESUMO
El esfriamiento brusco de la médula espinal aislada de sapos induce una convulsión característica en los miembros posteriores. En este trabajo, el kinurenato (KYN), un antagonista no competitivo de los receptores N-metil-D-aspartato (NMDA) y el 20amino-5-fosfonovalerato (APV), un antagonista competitivo de los receptores NMDA, fueron ensayados en el patrón, la latencia y la duración de esta convulsión espinal. APV, 1,3-2,5 mmol/Kg and KYN, 2,6 mmol/Kg, inhibieron la fase tónica de esta convulsión y prolongaron la duración de la fase clónica después de la administración intralinfática (i.l.). El mismo efecto fue observado después de la inyección intratecal de dosis de 10 ó 20 Amol/20 Al de cada droga. La fase clónica fue maracadamente atenuada por KYN a dosis altas de 5.3 ó 10.6 mmol/Kg, i.l., sugiriendo que receptores del tipo no NMDA podrían tener alguna mediciación en la generación de dicha fase. Ambos antagonistas retardaron el comienzo de las convulsiones, indicando que la activación de los receptores NMDA están probablemente involucrados en el comienzo de este tipo de convulsiones. Este modelo espinal podría ser una técnica útil para el ensayo de otros antagonistas de amino ácidos excitatorios (AU)