Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 107
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Molecules ; 24(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609687

RESUMO

A drug design for safer phenylbutazone was been explored by reactivity and docking studies involving single electron transfer mechanism, as well as toxicological predictions. Several approaches about its structural properties were performed through quantum chemistry calculations at the B3LYP level of theory, together with the 6-31+G(d,p) basis sets. Molecular orbital and ionization potential were associated to electron donation capacity. The spin densities contribution showed a preferential hydroxylation at the para-positions of phenyl ring when compared to other positions. In addition, on electron abstractions the aromatic hydroxylation has more impact than alkyl hydroxylation. Docking studies indicate that six structures 1, 7, 8 and 13⁻15 have potential for inhibiting human as well as murine COX-2, due to regions showing similar intermolecular interactions to the observed for the control compounds (indomethacin and refecoxib). Toxicity can be related to aromatic hydroxylation. In accordance to our calculations, the derivatives here proposed are potentially more active as well safer than phenylbutazone and only structures 8 and 13⁻15 were the most promising. Such results can explain the biological properties of phenylbutazone and support the design of potentially safer candidates.


Assuntos
Fenilbutazona/química , Fenilbutazona/farmacologia , Descoberta de Drogas/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Fenilbutazona/efeitos adversos , Fenilbutazona/toxicidade , Relação Estrutura-Atividade
2.
J Vet Med Sci ; 81(3): 418-424, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30674748

RESUMO

Equine Glandular Gastric Disease (EGGD) is a common disease in sport horses. This disease might be associated with usage of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating inflammatory diseases. Although gastroscopy has been an effective method for diagnosis, but a less invasive, and inexpensive method is preferred. This study used proteomic technology to identify candidate serum proteins that might be used as markers of NSAIDs induced EGGD. Five Thoroughbred horses were given high doses of NSAID, phenylbutazone to treat lameness. The experiment was divided into three periods: (i) Pre-EGGD period, (ii) during EGGD period, and (iii) Post-EGGD period. Gastroscopy were used to diagnose EGGD, serum was collected to perform gel electrophoresis (1D SDS-PAGE) and mass spectrometry (LC-MS) in order to identify serum proteins in each group. The candidate serum proteins were computationally predicted for the interaction between phenylbutazone and proteins, tissue specific expression, and association to gastric ulceration. After EGGD induction, all horses showed clinical signs of colic with marked congestion and erosion appearing in the mucosa of the glandular stomach whereas no change was observed in the mucosa of non-glandular stomach. Our proteomic results identified 14 proteins that might be used as EGGD markers. These proteins were highly expressed in the glandular stomach and some proteins were associated with phenylbutazone or ulcer development. However, confirmation of these candidate marker proteins is required with specific antibodies in the larger horse population before they can be considered for application in the field.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Proteínas Sanguíneas/metabolismo , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/toxicidade , Gastropatias/induzido quimicamente , Animais , Proteínas Sanguíneas/genética , Cavalos , Masculino
4.
Altern Lab Anim ; 41(3): 235-48, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23971704

RESUMO

Published in silico, in vitro, in vivo laboratory animal and human data, together with information on biotransformation and data from structure-activity analyses with two decision-tree systems (ACToR and Toxtree), have been used in a weight-of-evidence (WoE) assessment to determine whether phenylbutazone (PBZ) is a genotoxic or a non-genotoxic carcinogen. This was undertaken to facilitate the risk assessment of human exposure to this veterinary drug via the consumption of horsemeat from treated animals. Despite problems with data interpretation at all tiers of the database, it was concluded that PBZ behaves like a genotoxic carcinogen with a threshold dose. This conclusion is based mainly on the results of a definitive rodent bioassay, and on the following observations: a) that PBZ has weak in vitro activity only at high concentrations in some genotoxicity assays, accompanied by high levels of cytotoxicity; b) that it (and a major metabolite) is able to cause sister chromatid exchanges in vivo in rodents; and c) that it can induce cytogenetic effects in vivo in humans. It also takes into account the known and predicted activities of the parent drug, some of its metabolites and two structural analogues, and, importantly, several of the drug's other biochemical effects that are unrelated to toxicity. However, this conclusion is not fully supported by all the evidence, and much of the information is based on old papers. Therefore, more studies are required to establish whether the concentration thresholds seen in vitro would translate to dose thresholds for carcinogenicity, such that a safe dose-level could be defined for the purposes of assessing risk. It was disappointing that a WoE approach to evaluating all of the available hazard data, as is increasingly being advocated to improve the hazard identification paradigm, was unable to provide definitive answers in this case, particularly in view of the large numbers of animals that had been used to provide much of the information.


Assuntos
Carcinógenos/toxicidade , Mutagênicos/toxicidade , Fenilbutazona/toxicidade , Animais , Biotransformação , Humanos , Testes de Mutagenicidade , Fenilbutazona/farmacocinética , Relação Estrutura-Atividade
5.
Vet J ; 196(3): 294-303, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23721873

RESUMO

The presence of horse meat in food products destined for human consumption and labelled as beef has raised several concerns of public interest. This review deals solely with one aspect of these concerns; samples of equine tissue from horses destined for the human food chain have tested positive for the non-steroidal anti-inflammatory drug, phenylbutazone. The safety of some or all such foods for human consumers is a major concern, because it was shown many years ago that phenylbutazone therapy in humans can be associated with life threatening blood dyscrasias. As an initial basis for assessing the potential toxicity of foods containing phenylbutazone and its metabolites, this article reviews (1) the pharmacokinetic, pharmacodynamic, metabolic and toxicological profiles of phenylbutazone, with particular reference to horses and humans; (2) toxicity data in laboratory animals; (3) phenylbutazone residues in food producing species, and (4) as a preliminary assessment, the potential hazard associated with the consumption of horse meat containing phenylbutazone and its metabolites. Since phenylbutazone cannot be classified as a carcinogenic substance in humans, and noting that blood dyscrasias in humans are likely to be dose and treatment duration-dependent, the illegal and erratic presence of trace amount residues of phenylbutazone in horse meat is not a public health issue.


Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacocinética , Cavalos/metabolismo , Fenilbutazona/metabolismo , Fenilbutazona/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/toxicidade , Resíduos de Drogas , Cavalos/sangue , Humanos , Fenilbutazona/sangue , Fenilbutazona/toxicidade
7.
Toxicology ; 303: 1-8, 2013 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-23142791

RESUMO

Renal papillary injury is a common side effect observed during nonclinical and clinical investigations in drug development. The present study aimed to identify genomic biomarkers for early and sensitive detection of renal papillary injury in rats. We hypothesized that previously identified genomic biomarkers for tubular injury might be applicable for the sensitive detection of papillary injury in rats. We selected 18 genes as candidate biomarkers for papillary injury based on previously published studies and analyzed their expression profiles by RT-PCR in each kidney region, namely the cortex, cortico-medullary junction, and papilla in various nephrotoxicity models. Comparative analysis of gene expression profiles revealed that some genes were commonly upregulated or downregulated in the renal papilla, reflecting papillary injuries induced by 2-bromoethylamine hydrobromide, phenylbutazone, or n-phenylanthranilic acid. By applying receiver operator characteristics analysis, six candidate biomarkers were identified and their usefulness was confirmed by using an independent data set. The three top-ranked genes, Timp1, Igf1, and Lamc2, exhibited the best prediction performance in an external data set with area under the curve (AUC) values of greater than 0.91. An optimized support vector machine model consisting of three genes achieved the highest AUC value of 0.99. In conclusion, even though definitive validation studies are required for the establishment of their usefulness and reliability, these identified genes may prove to be the most promising candidate genomic biomarkers of renal papillary injury in rats.


Assuntos
Fator de Crescimento Insulin-Like I/genética , Nefropatias/induzido quimicamente , Medula Renal/efeitos dos fármacos , Laminina/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Animais , Área Sob a Curva , Regulação para Baixo/efeitos dos fármacos , Etilaminas/toxicidade , Perfilação da Expressão Gênica , Marcadores Genéticos , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/genética , Nefropatias/patologia , Medula Renal/patologia , Masculino , Fenilbutazona/toxicidade , Curva ROC , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Toxicogenética/métodos , Regulação para Cima/efeitos dos fármacos , ortoaminobenzoatos/toxicidade
8.
J Vet Intern Med ; 26(6): 1494-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23083114

RESUMO

BACKGROUND: Newer NSAIDs that more selectively target the induced isoform of the cyclooxygenase enzyme (COX2) activity might reduce adverse effects while preserving therapeutic benefits of these drugs. OBJECTIVES: To compare the effect of oral administration of multiple dose rates of meloxicam and phenylbutazone (PBZ) on gastric mucosal integrity in horses. ANIMALS: Twenty-five light breed horses. METHODS: In vivo toxicity study. Horses were randomly assigned to 5 treatment groups, receiving placebo, PBZ (4.4 mg/kg PO q12h day 1, 2.2 mg/kg PO q12h for 4 days, 2.2 mg/kg PO q24h for 9 days), or 3 dose rates of meloxicam (0.6 mg/kg q24h, 1.8 mg/kg q24h, 3.0 mg/kg q24h) for 14 days. Sucrose permeability testing was performed on Day 0 (before treatment) and on Day 13. All personnel involved with data collection or analysis were blinded to treatment. RESULTS: Administration of PBZ at the above dose rate significantly increased gastric permeability to sucrose, evidenced by increased peak serum sucrose concentrations (280-1,580 pg/µL, P = .001) after treatment. Similar changes were not evident after administration of meloxicam at any dose rate tested, or in control horses (P > .05). Treatment was not associated with significant differences in ulceration of the squamous or glandular mucosa. Peak sucrose concentrations were not correlated with serum total protein or albumin concentrations (R(2) = -0.07, P = .61, R(2) = -0.08, P = .58, respectively). CONCLUSION AND CLINICAL IMPORTANCE: These results suggest that PBZ was associated with greater compromise to gastric mucosal integrity than meloxicam.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/toxicidade , Tiazinas/toxicidade , Tiazóis/toxicidade , Animais , Feminino , Cavalos , Masculino , Meloxicam , Permeabilidade , Sacarose
9.
Ces med. vet. zootec ; 6(1)ene.-jun. 2011. ilus
Artigo em Espanhol | LILACS | ID: lil-616474

RESUMO

Se describe el caso de un equino que desarrolló graves lesiones digestivas después de recibir dosis altasde fenilbutazona (FBZ) para tratar una claudicación. Al momento de la consulta tenía 9 días de evolución.Desde su llegada al hospital, se observó cojera grave de las cuatro extremidades, deshidratación y diarreafétida. Luego del examen físico, la anamnesis y las ayudas diagnósticas se propuso un dictamen de laminitis traumática, gastritis ulcerativa y colitis por intoxicación con antiinflamatorios no esteroides (AINES). Lacondición empeoró a pesar de la terapia y cuando se presentaron signos neurológicos se sugirió la eutanasia.Durante la necropsia se observaron lesiones graves en el tracto gastrointestinal, cascos y encéfalo. El objetivo de este artículo es describir la sintomatología, terapia y evolución de un paciente intoxicado con aines.


It is described a clinic case of an equine that developed severe digestive lesions after taking high dosage ofphenylbutazone to treat a lameness. At the moment of checking, it had nine days of evolution. Since its arrivingto the hospital, it was seen an intense lameness of the four limbs, dehydration and fetid diarrhea. After the physicexam, the interrogatory and the diagnostic aids it was proposed a diagnosis of traumatic laminitis, ulcerative gastritis and colitis by intoxication with Non-steroidal anti-inflamatory drug (NSAIDs). The condition became worse despite the therapy and when the neurological signs were presented. It was suggested the euthanasia. During the necropsy, it was seen severe lesions in the gastrointestinal tract, hooves and brain. The objective of this article is to describe la symptomatology, therapy and evolution of the intoxicated patient with NSAIDs.


Descreve-se o caso de um cavalo que desenvolveu lesões digestivas graves após receber altas doses defenilbutazona (FBZ) para tratar uma claudicação. No momento da consulta havia 9 dias de evolução. Desdesua chegada ao hospital, observou-se manqueira grave nas quatro extremidades, desidratação e diarréia fétida. Após o exame físico, a anamnese e os meios diagnósticos concluiu-se se tratar de laminite traumática, gastriteulcerativa e colite por intoxicaçãocom anti-inflamatórios não esteróides (AINES). A condição piorou apesardo tratamento e, quando apresentou sinais neurológicos, sugeriu-se a eutanásia. Na necrópsia observaram-selesões graves no trato gastrointestinal, cascos e enféfalo. O objetivo deste trabalho é descrever os sintomas, otratamento e a evolução de um paciente intoxicado com AINES.


Assuntos
Animais , Claudicação Intermitente/veterinária , Coxeadura Animal/complicações , Envenenamento/veterinária , Fenilbutazona/toxicidade , /veterinária , Administração de Caso , Registros Médicos
10.
Am J Vet Res ; 69(11): 1496-505, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18980433

RESUMO

OBJECTIVE: To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC). ANIMALS: 12 healthy adult horses. PROCEDURES: A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E(2) (PGE(2)) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance. RESULTS: Data from 8 horses were analyzed. Plasma albumin concentrations decreased significantly from days 10 to 21 during phenylbutazone treatment, compared with results during the same days for the control treatment. Phenylbutazone treatment caused neutropenia (< 3.0 x 10(3) cells/microL). No other clinical or hematologic abnormalities were detected for phenylbutazone or control treatments. Two horses developed colitis while receiving phenylbutazone. No significant differences were detected in the RDC between phenylbutazone and control treatments for MPO activity, MDA and PGE(2) concentrations, and histologic evidence of inflammation. Arterial blood flow in the RDC was significantly increased during phenylbutazone treatment, compared with values for the control treatment. Differences were identified in VFA production during phenylbutazone treatment, compared with the control treatment, with a decrease in acetic acid concentrations over time. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged phenylbutazone administration caused hypoalbuminemia, neutropenia, changes in RDC arterial blood flow, and changes in VFA production. Veterinarians should monitor serum albumin concentrations and neutrophil counts and be cautious when making dosing recommendations for phenylbutazone treatment of horses.


Assuntos
Colite/veterinária , Colo/efeitos dos fármacos , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/patologia , Fenilbutazona/toxicidade , Animais , Colite/induzido quimicamente , Colite/patologia , Colo/irrigação sanguínea , Colo/fisiopatologia , Estudos Cross-Over , Ácidos Graxos/metabolismo , Cavalos , Malondialdeído/metabolismo , Peroxidase/metabolismo , Prostaglandinas E/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de Tempo
11.
Biochem Pharmacol ; 74(1): 74-85, 2007 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-17499219

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) contribute to gastrointestinal ulcer formation by inhibiting epithelial cell migration and mucosal restitution; however, the drug-affected signaling pathways are poorly defined. We investigated whether NSAID inhibition of intestinal epithelial migration is associated with depletion of intracellular polyamines, depolarization of membrane potential (E(m)) and altered surface expression of K(+) channels. Epithelial cell migration in response to the wounding of confluent IEC-6 and IEC-Cdx2 monolayers was reduced by indomethacin (100 microM), phenylbutazone (100 microM) and NS-398 (100 microM) but not by SC-560 (1 microM). NSAID-inhibition of intestinal cell migration was not associated with depletion of intracellular polyamines. Treatment of IEC-6 and IEC-Cdx2 cells with indomethacin, phenylbutazone and NS-398 induced significant depolarization of E(m), whereas treatment with SC-560 had no effect on E(m). The E(m) of IEC-Cdx2 cells was: -38.5+/-1.8 mV under control conditions; -35.9+/-1.6 mV after treatment with SC-560; -18.8+/-1.2 mV after treatment with indomethacin; and -23.7+/-1.4 mV after treatment with NS-398. Whereas SC-560 had no significant effects on the total cellular expression of K(v)1.4 channel protein, indomethacin and NS-398 decreased not only the total cellular expression of K(v)1.4, but also the cell surface expression of both K(v)1.4 and K(v)1.6 channel subunits in IEC-Cdx2. Both K(v)1.4 and K(v)1.6 channel proteins were immunoprecipitated by K(v)1.4 antibody from IEC-Cdx2 lysates, indicating that these subunits co-assemble to form heteromeric K(v) channels. These results suggest that NSAID inhibition of epithelial cell migration is independent of polyamine-depletion, and is associated with depolarization of E(m) and decreased surface expression of heteromeric K(v)1 channels.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Superfamília Shaker de Canais de Potássio/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Cromatografia Líquida de Alta Pressão , Humanos , Indometacina/toxicidade , Mucosa Intestinal/metabolismo , Nitrobenzenos/toxicidade , Técnicas de Patch-Clamp , Fenilbutazona/toxicidade , Poliaminas/análise , Poliaminas/metabolismo , Superfamília Shaker de Canais de Potássio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Espectrometria de Massas por Ionização por Electrospray , Sulfonamidas/toxicidade , Cicatrização/fisiologia
12.
Res Vet Sci ; 76(2): 145-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14672858

RESUMO

The objective was to compare the gastrointestinal and general toxicity of suxibuzone (SBZ) to that of phenylbutazone (PBZ) when administered orally in horses. Fifteen healthy horses were allocated to three treatment groups. One group received a high dose of PBZ for two weeks; the second group was given an equimolecular dosage of SBZ; and a third group received placebo. Horses were daily monitored, and blood samples were collected before and during the study. On day 18, complete post-mortem examinations were performed. One horse treated with PBZ showed clinical signs of NSAID toxicosis. Small oral ulcers were also detected in other two horses from the PBZ group and in two horses from the SBZ group. There were no statistical differences in the blood parameters among groups. Ulcers in the stomach's glandular mucosa were observed in all horses of the PBZ group, while only two horses of the SBZ group showed ulcerations. PBZ horses had a significant higher ulcerated area, and gastric ulcers were significantly deeper than those in the SBZ and placebo groups. No other lesions were found in any other tissue. In conclusion, SBZ causes significantly lower gastric ulcerogenic effect than PBZ when administered orally at equimolecular doses in horses.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Doenças dos Cavalos/induzido quimicamente , Fenilbutazona/análogos & derivados , Fenilbutazona/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/veterinária , Animais , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Doenças dos Cavalos/patologia , Cavalos , Masculino , Úlcera Gástrica/patologia
13.
Eksp Klin Farmakol ; 63(6): 49-52, 2000.
Artigo em Russo | MEDLINE | ID: mdl-11202513

RESUMO

Experiments on various animals showed that fensulkal, a new phenylglyoxylic acid derivative, possesses a high antiinflammatory activity and low toxicity, markedly exceeding butadion in the therapeutic index. The mechanism of the antiphlogistic effect of fensulkal is due to its antagonism with respect to mediators of the inflammatory process and the ability of suppressing the increased permeability of capillaries and is partly related to the adrenal cortex. The drug is registered and recommended for application as antiinflammatory remedy in the form of ointment to be used for the treatment of some gynecological disorders.


Assuntos
Acetatos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Ácidos Sulfônicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/toxicidade , Artrite/induzido quimicamente , Artrite/tratamento farmacológico , Queimaduras/tratamento farmacológico , Gatos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Dose Letal Mediana , Camundongos , Medição da Dor , Peritonite/tratamento farmacológico , Fenilbutazona/uso terapêutico , Fenilbutazona/toxicidade , Coelhos , Ratos , Testes de Toxicidade Aguda
14.
Arzneimittelforschung ; 49(10): 843-8, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10554662

RESUMO

The anti-inflammatory effects of five pyrazolidine derivatives on white mice and laboratory rats were studied using models of thermal aseptic inflammation and inflammation induced by injection of carragenin and histamine, as well as models of "cotton-ball granuloma" and epinephrine (adrenaline)-induced pulmonary edema. These effects were compared with those of the most commonly used non-steroid anti-inflammatory drugs, such as phenylbutazone (CAS 50-33-9) and diclofenac (CAS 15307-79-6). It was found that the pyrazolidine compounds studied induced a pronounced anti-inflammatory effect by inhibiting both the proliferative and exudative phases of inflammation. At the same time, as compared to natural non-steroid anti-inflammatory drugs, these compounds had a lower toxicity and induced neither gastric ulcers nor suppression of hemopoiesis.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Pirazóis/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Contagem de Células Sanguíneas/efeitos dos fármacos , Carragenina , Edema/induzido quimicamente , Edema/prevenção & controle , Epinefrina , Exsudatos e Transudatos/citologia , Exsudatos e Transudatos/efeitos dos fármacos , Feminino , Gossypium , Granuloma/induzido quimicamente , Granuloma/prevenção & controle , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Dose Letal Mediana , Masculino , Camundongos , Fenilbutazona/toxicidade , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/prevenção & controle , Pirazóis/farmacologia , Pirazóis/toxicidade , Ratos , Úlcera Gástrica/induzido quimicamente , Vasoconstritores
15.
Drug Chem Toxicol ; 22(3): 563-7, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10445165

RESUMO

The lethal dose curve of phenylbutazone was assayed in control animals (A) and in animals in which an experimental arthritis had been produced by injection of Feund's complete adjuvant (B). Thirty male Wistar rats 3 months old were divided into two groups of 15 rats each: group A consisted of the control group and group B the adjuvant treated group. Arthritis was produced by a single injection of 0.15 Freund's complete adjuvant on the right footpad. The control group was injected with the adjuvant vehicle at the same site. Injections of 200 mg/kg of phenylbutazone once daily for ten days started fifteen days after administration of Freund's adjuvant. After the first injection of phenylbutazone the LD6.6 in group A corresponded to LD53 in group B while after the second injection the LD46.6 for the control group corresponded to LD100 in group B. We assume that the therapeutic index would be more representative if lethal dose curves were evaluated in animals suffering from a disease that the drug in question has been designated for.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Artrite Experimental/tratamento farmacológico , Fenilbutazona/toxicidade , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
16.
Mutat Res ; 420(1-3): 15-25, 1998 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-9838026

RESUMO

Phenylbutazone (PB), oxyphenbutazone (OPB), antipyrine (AP) and dipyrone (DP) are four important pyrazolone derivatives mainly used as anti-inflammatory, antipyretic and analgesic drugs. At present these are the most widely used pyrazolone derivatives throughout the world. The widespread use of these drugs are of great concern for human health problems. In the present study these four drugs were tested in mutagenicity assays in Salmonella strains TA97a, TA98, TA100 and TA102 using a plate incorporation assay both with and without S-9 mix and for in vivo sister chromatid exchanges (SCE) in bone marrow cells of mice. The first three drugs were negative in all the tester strains but dipyrone showed a weak mutagenic activity at higher concentrations in all four strains both with and without metabolic activation. In the in vivo SCE assay in male mice, all four drugs showed a statistically significant increase in SCE in bone marrow cells when compared with control.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Pirazóis/toxicidade , Pirazolonas , Salmonella/genética , Troca de Cromátide Irmã/genética , Animais , Antipirina/toxicidade , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Dipirona/toxicidade , Fígado/patologia , Masculino , Camundongos , Testes de Mutagenicidade , Oxifenilbutazona/toxicidade , Fenilbutazona/toxicidade , Ratos
17.
Can Vet J ; 39(10): 647-9, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9789678

RESUMO

This report describes a renal ultrasonographic abnormality (medullary rim sign), which was identified in 2 separate cases of spontaneously occurring disease associated with chronic and acute overdosage of phenylbutazone therapy. In horses, medullary rim sign has only been documented in neonatal foals experimentally administered large doses of phenylbutazone.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Doenças dos Cavalos/induzido quimicamente , Nefropatias/veterinária , Medula Renal/diagnóstico por imagem , Fenilbutazona/toxicidade , Animais , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico por imagem , Masculino , Ultrassonografia
18.
Dtsch Tierarztl Wochenschr ; 103(1): 14-6, 1996 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-8647008

RESUMO

Tolerance and pharmacokinetics of a combination of phenylbutazone and prednisolone (tablets) were studied in Beagle dogs. For two weeks, the drug was administered orally (3.33 mg/kg phenylbutazone combined with 0.1 mg/kg prednisolone and 6.66 mg/kg phenylbutazone combined with 0.3 mg/kg prednisolone twice daily). The dosage was reduced to 50 per cent after one week. No signs of intolerance were found. After treatment with 3.33 mg/kg phenylbutazone, a plasma concentration of 10 micrograms/ml was reached within 1 to 2 hours. No prednisolone concentration above 2 ng/kg was measured. Additionally, a synergistic antiinflammatory effect of the two ingredients was obvious (hind paw dextran edema in rats). In addition to results of ENGELKE et al. (1995) who studied the clinical efficacy of the combination, the presented data demonstrate a good tolerance.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios/farmacocinética , Cães/metabolismo , Fenilbutazona/farmacocinética , Prednisolona/farmacocinética , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/toxicidade , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/toxicidade , Combinação de Medicamentos , Feminino , Masculino , Fenilbutazona/administração & dosagem , Fenilbutazona/toxicidade , Prednisolona/administração & dosagem , Prednisolona/toxicidade , Comprimidos
19.
Jpn J Cancer Res ; 86(3): 252-63, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7744695

RESUMO

Long-term toxicity and carcinogenicity of phenylbutazone, a nonsteroidal anti-inflammatory drug, were evaluated in F344/N rats and B6C3F1 mice. In 2-year studies, phenylbutazone was given in corn oil by gavage 5 days per week to groups of 50 rats of each sex at doses of 0, 50, or 100 mg/kg body weight, and to groups of 50 mice at doses of 0, 150, or 300 mg/kg body weight. Body weights and survival were similar among groups. Major target organs are kidneys in rats and liver in mice. Kidney: inflammation, papillary necrosis, and mineralization in both sexes of rats, and hyperplasia and dilatation of the pelvis epithelium, and cysts in female rats. Uncommon tubular cell tumors of the kidney were found in 13 exposed rats: 5 in the 50 mg group and 4 in the 100 mg group of males; 4 in dosed female rats; none in controls. In female rats, dose-related increases in hyperplasia of the pelvis transitional epithelium, and 2 carcinomas were discovered. Urinary bladder: papillomas of the transitional epithelium were seen in 2 low-dose male and in 1 low-dose female rats. Forestomach: ulcers in rats, with acanthosis, hyperkeratosis, and basal cell hyperplasia in female rats; however, no neoplasms were associated with these lesions. Liver: primarily in male mice exposed to phenylbutazone, hemorrhage, centrilobular cytomegaly and karyomegaly, fatty metamorphosis, cellular degeneration, and coagulative necrosis were seen; clear cell foci were observed in male mice. In summary, under the conditions of these 2-year oral intubation studies, phenylbutazone is associated with renal carcinogenicity in rats, as evidenced by increases in tubular cell neoplasms in both sexes. Evidence of carcinogenicity for male mice was shown by increased incidences and multiplicity of liver tumors. No carcinogenic activity was found for female mice.


Assuntos
Neoplasias Renais/induzido quimicamente , Neoplasias Hepáticas/induzido quimicamente , Fenilbutazona/toxicidade , Adenoma/induzido quimicamente , Adenoma/patologia , Animais , Óleo de Milho , Feminino , Hiperplasia , Rim/patologia , Neoplasias Renais/patologia , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Fenilbutazona/administração & dosagem , Ratos , Ratos Endogâmicos F344 , Especificidade da Espécie
20.
J Am Vet Med Assoc ; 202(1): 71-7, 1993 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8420909

RESUMO

The relative toxicity of phenylbutazone, flunixin meglumine, and ketoprofen was studied in healthy adult horses. Sixteen horses were randomly assigned to receive 10 ml of physiologic saline solution, or ketoprofen (2.2 mg/kg of body weight), flunixin meglumine (1.1 mg/kg), or phenylbutazone (4.4 mg/kg) IV, every 8 hours, for 12 days. Results of CBC, serum biochemical analyses, and fecal occult blood tests were monitored. On day 13, all horses were euthanatized and complete necropsy examinations were performed. Mean CBC values remained within normal limits for all groups. Phenylbutazone-treated horses had a significant (P < 0.05) decrease in serum total protein and albumin concentrations. Mean values of all other serum biochemical assays were not different from those of the saline-treated group. Results of all fecal occult blood tests were negative. At necropsy, the glandular portion of the stomach was the area of the gastrointestinal tract most severely affected by phenylbutazone, flunixin meglumine, and ketoprofen. In the phenylbutazone-treated group, but not in the other groups, edema of the small intestine and erosions and ulcers of the large colon were observed. None of the horses treated with saline solution had lesions in the glandular portion of the stomach or in the intestine. Four horses (1/5 and 3/3 in the flunixin- and phenylbutazone-treated groups, respectively) developed renal crest necrosis. Horses in the saline- and ketoprofen-treated groups did not develop renal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Clonixina/análogos & derivados , Doenças dos Cavalos/induzido quimicamente , Cetoprofeno/toxicidade , Fenilbutazona/toxicidade , Animais , Anorexia/induzido quimicamente , Anorexia/veterinária , Proteínas Sanguíneas/efeitos dos fármacos , Clonixina/toxicidade , Feminino , Mucosa Gástrica/efeitos dos fármacos , Gastroscopia/veterinária , Cavalos , Pelve Renal/efeitos dos fármacos , Masculino , Doenças da Boca/induzido quimicamente , Doenças da Boca/veterinária , Mucosa Bucal/efeitos dos fármacos , Necrose , Distribuição Aleatória , Gastropatias/induzido quimicamente , Gastropatias/veterinária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...