Avaliações hematológicas e bioquímicas do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos / Evaluations hematological and biochemical by the use of sodium diclofenac, meloxicam and firocoxib in rats

O presente trabalho avaliou os parâmetros hematológicos e bioquímicos do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos Wistar. Os ratos foram distribuídos em grupos: G1 (controle), G2 (diclofenaco de sódio: 15 mg/kg), G3 (meloxicam: 2,0 mg/ kg), G4 (meloxicam: 10,0 mg/ kg), G5 (firocoxibe: 5,0 mg/ kg) e G6 (firocoxibe: 25,0 mg/ kg). Os fármacos foram administrados por via intragástrica (gavage) a cada 24 horas, durante cinco dias e avaliados em três momentos: M1 (48 horas após o início do tratamento), M2 (96 horas após o início do tratamento) e M3 (72 horas após o término do tratamento). Em cada momento de cada grupo, foram avaliados de cinco a sete animais e realizados os exames laboratoriais. Não foram observadas alterações significativas nos parâmetros bioquímicos e hematológicos com o uso de meloxicam e firocoxibe. O diclofenaco de sódio produziu alterações no eritrograma (redução de hemácias, hematócrito e na taxa de hemoglobina) durante o tratamento e não alterou a contagem das plaquetas e leucometria, com exceção dos basófilos. Não produziu alterações nas atividades de AST, FA, GGT, ureia, creatinina, sódio e potássio. Entretanto, causou diminuições das proteínas plasmática e total sérica, albumina e globulina. Conclui-se que o diclofenaco de sódio não produz grandes alterações no hemograma e exames bioquímicos, enquanto que, o meloxicame o firocoxibe não produzem alterações e efeitos deletérios dose-dependentes nestes exames laboratoriais.

This work has evaluated the hematological and biochemical profile by the use of sodium diclofenac, meloxicam and firocoxib in Wistar rats. The rats were distributed in groups: G1 (control), G2 (diclofenac sodium: 15 mg/kg), G3 (meloxicam: 2.0 mg/ kg), G4 (meloxicam: 10.0 mg/ kg), G5 (firocoxib: 5.0 mg/ kg) e G6 (firocoxib: 25.0 mg/ kg). The drugs were administered intragastrically (gavage) once a day, during five days and evaluated in three moments: M1 (48 hours after the beginning of the treatment), M2 (96 hours after the beginning of the treatment) and M3 (72 hours after the ending of the treatment). In each moment of each group, five to seven animals were evaluated and laboratory exams were performed. There were no significant changes observed in the biochemical and hematological parameters by the use of meloxicam and firocoxib. One of the effects of the sodium diclofenac was eritrogram variation as hematocrit, erythrocytes, hemoglobin decrease during the treatment. In addition, the platelets and total white blood cells counts did not change except for basophil. There was no changes in AST, ALP, GGT, urea, creatinine, sodium, potassium values. However, the values of protein, globulin and albumin decreased. It was concluded that diclofenac sodium does not provide large variations in the hemogram and biochemical profile than the meloxicam and firocoxib do not provide delletery effects in laboratories tests.

Effect of Mikania glomerata (Asteraceae) leaf extract combined with anti-venom serum on experimental Crotalus durissus (Squamata: Viperidae) envenomation in rats

Crotalic envenomation represents the highest number of deaths when compared to other snakebite envenomations of medical interest. Crotalic venom has important characteristics such as neurotoxicity, myotoxicity, nephrotoxicity, and clotting and hemolytic action. We evaluated the clinical and laboratory aspects of Crotalus durissus terrificus experimental envenomation in Wistar rats treated with antivenom and the aqueous extract of the plant Mikania glomerata. The animals were divided into three groups: Group C (control); Group VS-venom and antivenom; Group VSM-venom, antivenom and aqueous extract of M. glomerata. Crotalic poison caused clinical and laboratory alterations in Wistar mice. Significant linical alterations were: temperature decrease, edema in the venom inoculated member, sedation and a locomotion decrease in groups VS and VSM when compared with group C. A faster recovery from sedation was observed only for animals of group VSM when compared to VS. There was an increase in the number of leukocytes, neutrophils and creatine kinase in the VS and VSM groups, compared to group C. Wistar rats showed a high resistance to crotalic venom. Additional studies with different doses, time of treatment, different administration methods and histopathological and immunological studies are necessary to understand the action of M. glomerata in crotalic accidents. Rev. Biol. Trop. 57 (4): 929-937. Epub 2009 December 01.

El envenamiento crotálico representa el número más alto de muertes cuando es comparado con envenenamientos por mordeduras de otras serpientes de interés médico. El veneno crotálico tiene importantes características de acción neurotóxica, miotoxicidad, nefrotoxicidad, coagulación y acción hemolítica. Este trabajo evaluó los aspectos clínicos y de laboratorio del envenenamiento experimental con el veneno de la serpiente Crotalus durissus terrificus en las ratas Wistar tratadas con suero antiofídico y extracto acuoso de M. glomerata. Los animales fueron separados en tres diferentes grupos: grupo control (C); grupo veneno+suero (VS), grupo veneno+suero+extracto acuoso de M. glomerata (VSM). El veneno crotálico causó alteraciones clínicas y diferencias en los análisis sanguíneos practicados a los ratones Wistar evaluados. Las alteraciones clínicas más importantes fueron una disminución de la temperatura, edema en el miembro inoculado de veneno, la sedación y una disminución de la locomoción en los grupos VS y VSM comparado con el grupo C. Una rápida recuperación de la sedación estadísticamente significativa fue observada en los animales del grupo VSM al compararse con los del grupo VS. Los análisis sanguíneos mostraron un aumento en el número de leucocitos, neutrofilos y creatina quinasa en los grupos VS y VSM comparados con el grupo C. Los ratones Wistar mostraron una alta resistencia al veneno del crótalo. Estudios adicionales con variación en las dosis, tiempo de tratamiento, y métodos de administración, así como la realización de estudios histopatológicos e inmunológicos son importantes para comprender la acción de M. glomerata en accidentes crotálicos.

Dosagem de marcadores cardíacos CK-MB e TnIc e eletrólitos no envenenamento experimental por veneno de sapo em cães / Determination of cardiac markers and CK-MB TnIc and electrolyte in experimental poisoning by poison frog in dogs

Dentre os sinais sistêmicos causados pelo envenenamento por veneno de sapo (bufotoxina) em cães, os efeitos cardiotóxicos são um dos mais importantes. O objetivo deste estudo foi avaliar as potenciais alterações no músculo cardíaco de cães envenenados experimentalmente por veneno de sapo e observar as alterações eletrolíticas que podem ocorrer nesse tipo de envenenamento. Utilizaram-se 20 cães divididos em grupo controle (n=5) e grupo envenenado (n=15). O veneno de sapo foi extraído por meio de compressão manual das glândulas paratóides. Após anestesia geral, os cães do grupo controle receberam placebo (solução fisiológica) e os do grupo envenenado uma alíquota do veneno por sonda orogástrica. As colheitas de sangue para dosagem dos marcadores cardíacos foram realizadas seis e 24 horas após o envenenamento. As colheitas de sangue para dosagem dos eletrólitos foram realizadas antes e duas, quatro, seis e 12 horas após o envenenamento. A análise estatística empregada foi o teste não-paramétrico de Mann-Withney (P<0,05). Os cães envenenados por veneno de sapo apresentaram elevação dos níveis dos marcadores cardíacos CK-MB e TnIc, confirmando a cardiotoxicidade do veneno. Hipocalemia e hipocalcemia foram também observadas nos cães envenenados.

Among the systemic signs of toad venom (bufotoxin) poisoning in dogs, the cardiotoxic effects are one of the most important. Thus, the objective of this experiment was to evaluate potential changes in the cardiac muscle in dogs poisoned experimentally by toad venom and to observe the eletrolyte alterations which may occur in this condition. Twenty dogs divided into control group (n=5) and poisoned group (n=15) were utilized. The toad venom was extracted by manual compression of the paratoidic glands. After general anesthesia, dogs in the control group received placebo and dogs in the poisoned group received the venom by orogastric catheter. Samples for dosage were collected 6 hours and 24 hours after poisoning and 0, 2, 4, 6 and 12 hours after poisoning for electrolytes dosage. The Man-Withney test was used for statistical analysis (P<0.05). The poisoned dogs showed (saline) elevated levels of cardiac markers CK-MB and TnIc, confirming the cardiotoxic effect of the bufotoxin. Hypokalemia and hypocalcemia were also observed.

Effect of Mikania glomerata (Asteraceae) leaf extract combined with anti-venom serum on experimental Crotalus durissus (Squamata: Viperidae) envenomation in rats.

Crotalic envenomation represents the highest number of deaths when compared to other snakebite envenomations of medical interest. Crotalic venom has important characteristics such as neurotoxicity, myotoxicity, nephrotoxicity, and clotting and hemolytic action. We evaluated the clinical and laboratory aspects of Crotalus durissus terrificus experimental envenomation in Wistar rats treated with antivenom and the aqueous extract of the plant Mikania glomerata. The animals were divided into three groups: Group C (control); Group VS-venom and antivenom; Group VSM-venom, antivenom and aqueous extract of M. glomerata. Crotalic poison caused clinical and laboratory alterations in Wistar mice. Significant clinical alterations were: temperature decrease, edema in the venom inoculated member, sedation and a locomotion decrease in groups VS and VSM when compared with group C. A faster recovery from sedation was observed only for animals of group VSM when compared to VS. There was an increase in the number of leukocytes, neutrophils and creatine kinase in the VS and VSM groups, compared to group C. Wistar rats showed a high resistance to crotalic venom. Additional studies with different doses, time of treatment, different administration methods and histopathological and immunological studies are necessary to understand the action of M. glomerata in crotalic accidents.

Variabilidade clínica na determinação da dose tóxica oral em intoxicação experimental por fluoroacetato de sódio em gatos / Clinical variability in the determination of oral toxic dosis in the experimental intoxication with sodium fluoroacetate in cats

O fluoroacetato de sódio (FAS) ou composto 1080 é um potente rodenticida utilizado no controle de roedores e predadores manúferos. Sua utilização está proibida por lei em diversos países devido à sua alta toxicidade, mas no Brasil há evidências do uso ilegal e sem critérios causando intoxicações, principalmente em crianças e animais domésticos. O FAS age por meio do seu metabólito tóxico, o fluorocitrato, no bloqueio do ciclo de Krebs com consequente diminuição da produção de energia do organismo, provocando principalmente manifestações clínicas neurológicas e cardíacas. No presente estudo compararam quatro doses orais tóxicas do fluoroacetato de sódio, descritas em gatos, na literatura, observando-se o aparecimento dos sinais clínicos predominantes da intoxicação, as diferenças entre as doses quanto a variabilidade clínica em relação ao período de latência para o aparecimento dos sinais clínicos e sua respectiva intensidade. A dose oral tóxica que melhor caracterizou o quadro clínico da intoxicação por FAS em gatos, sem causar a letalidade aguda, foi de 0,4Smg/kg. As diferenças entre as manifestações clínicas foram dose-dependentes e em ordem crescente de intensidade, caracterizando-se como sinais leves (dose 1: 0,3mg/kg), leves a moderados (dose 2: 0,4mg/kg), moderados a graves (dose 3: 0,45mg/ kg) e graves (dose 4: 0,5mg/kg). Houve também variabilidade clínica individual entre animais intoxicados com a mesma dosagem do tóxico.

The sodium monofluoroacetate (FAC) or compound 1080 is a potent rodenticide used for a rodents and vertebrate pest control. lt was prohibited in many countties because of its high toxicity, but in Brazil exist evidences of ilegal use causing the intoxication in children and domestic animals. The fluoroacetate metabolite, fluorocitric acid, blocks body energy production by inhibit the Krebs cycle, resulting in neurological and cardiacs signs. ln the present study, four group of oral toxic dosis of the FAC were compared in cats. The best oral toxic dose for clinical signs presentation, without cause acute lethality, was 0,45mg/kg. The clinical variability was dosis dependent and its intensity , in crescent order, was: light signs (dose 1: 0,3mg/kg), light to moderate (dose 2: 0,4mg/kg), moderate to severe (dose 3: 0,45mg/ kg) and severe (dose 4: 0,5mg/kg). There was individual clinical variability between animals that received the same oral toxic dose.

The comparative efficacy of yohimbine and atipamezole to treat amitraz intoxication in dogs.

This study compared the efficacy of yohimbine with atipamezole, a new alpha2 adrenergic antagonist, to treat canine amitraz intoxication. Thirty dogs were divided equally into 3 groups (A, AY, and AA). Group A received 2.5% amitraz iv at 1 mg/kg; Group AY received the same dose of amitraz followed 30 min later by 0.1 mg/kg (2 mg/mL) yohimbine iv; and Group AA received the same dose of amitraz followed 30 min later by 0.2 mg/kg (5 mg/ mL) atipamezole iv. Temperature, heart rate, respiratory frequency, mean arterial pressure, degree of sedation, mean time of tranquilization and diameter of pupils were monitored for 360 min. Sedation, loss of reflexes, hypothermia, bradycardia, hypotension, bradypnea and mydriasis were observed in Group A, with 3rd eyelid prolapse, increased diuresis and vomiting in some animals. Yohimbine reversed all alterations induced by amitraz, but induced significant cardiorespiratory effects such as tachycardia and tachypnea. Atipamezole was a useful antagonist for amitraz, with less cardiorespiratory effects, suggesting its potential role as an alternative treatment of amitraz intoxication in dogs.

Evaluation of cardiac rhythm in dogs treated with levamisole hydrochloride using 24-hour ambulatory electrocardiography.

The objective of this study was to evaluate the electrocardiographic alterations in the cardiac rhythm in dogs treated with levamisole hydrochloride over a period of 24 hours. Thirty-six mixed-breed dogs, both male and female, all clinically healthy, were used in the experiment. The dogs were divided into 6 groups with 6 dogs in each group, according to dosage and route of administration. The Holter test was initiated immediately after the treatment, and was maintained for 24 hours. In the group treated with 10 mg/kg by way of subcutaneous injection, one of them showed ventricular premature complexes, sometimes isolated and other times in pairs, and ventricular tachycardia, concentrated mainly in the first hour after administration of the drug. In the group of 6 animals treated subcutaneously with 25mg/kg, four showed isolated ventricular premature complexes, ventricular bigeminy and trigeminy, mainly during the first 2 hours after administration of the drug. All the animals in the other groups showed sinus arrhythmia followed by sinus arrest. The disturbances in the cardiac rhythm observed in clinically healthy animals treated with levamisole hydrochloride, indicate that it is preferable to avoid subcutaneous administration of levamisole hydrochloride and that the oral administration of the drug should be done with caution.