RESUMEN
The trypanocidal potential of the natural chalcone flavokawin B, which was isolated from the hexanic extract of Polygonum ferrugineum Wedd., is reported here. Although flavokawin B is widespread, this is the first report about its trypanocidal properties on both Trypanosoma cruzi (IC50 = 9.5 µM, IC50 = 34.7 µM benznidazol, Y strain) epimastigotes and Trypanosoma brucei (IC50 = 4.8 µM, IC50 = 6.4 µM pentamidine, 29-13 strain) procyclic forms, which was also corroborated on T. brucei strain 427 (IC50 = 6.2 µM). In order to learn more about its properties, unspecific cytotoxicity on Hep G2 cells was investigated as well as the trans-splicing inhibitory potential on T. brucei cells. The results shown here point to flavokawin B as a candidate in the search for new agents. It is also cheaper and less toxic than the available drugs to treat trypanosomiasis with a special focus on sleeping sickness disease.
Asunto(s)
Flavonoides/farmacología , Tripanocidas/farmacología , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacos , Tripanosomiasis/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Chalcona/farmacología , Relación Dosis-Respuesta a Droga , Flavonoides/química , Flavonoides/aislamiento & purificación , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Polygonum/química , Tripanocidas/química , Tripanocidas/aislamiento & purificación , Trypanosoma brucei brucei/genética , Tripanosomiasis Africana/tratamiento farmacológicoRESUMEN
One of the ways to study cattle laminitis is its experimental induction by supplying a large amount of high fermentation carbohydrate. The most effective protocol until now has been the use of oligofructose. The objective of this study was to evaluate clinical and histological aspects of the hoof in experimental induction of ruminal acidosis and laminitis in calves using oligofructose. Six crossbred (Bos taurus x Bos indicus) yearling calves divided into Group I (GI) and Group II (GII) were used. Animals in GI and GII received intraruminal oligofructose in doses of 13 and 17g/kg, respectively. During 28 hours the calves were clinically evaluated and 30 hours after induction, samples were taken from coronary and abaxial wall of the hoof for histologic evaluation. Were noticed signs of ruminal and metabolic acidosis like rumen distension with fluid, diarrhea, ruminal pH reduction and, at blood gas analysis, pH and bicarbonate below reference range. Lameness was not observed however, some animals had a slower gait and apathy, possibly due to metabolic acidosis, though. Histologically, typical lesions of laminitis like circulatory changes and inflammatory infiltrate in the dermis, irregularities and areas of detachment at basement membrane and morphologic changes in cells from basal epidermis were found. The protocol induced, in the first 30 hours, clinical signs of ruminal and metabolic acidosis and low grade histologic lesions in the digits. Lameness and digit pain were not observed, characterizing the prodromic phase of the disease.(AU)
Uma das formas de se estudar a laminite bovina é sua indução experimental por meio do fornecimento de grande quantidade de carboidrato de alta fermentação. O protocolo mais eficaz até o momento foi o uso de oligofrutose. Objetivou-se avaliar aspectos clínicos e histológicos dos dígitos de bovinos na indução experimental de acidose ruminal e laminite usando oligofrutose. Utilizaram-se seis bezerros mestiços (Bos taurus x Bos indicus) de um ano, divididos em Grupo I (GI) e Grupo II (GII). Os animais em GI e GII receberam oligofrutose por via intrarruminal nas doses de 13 e 17g/kg respectivamente. Os bovinos foram avaliados clinicamente por 28 horas e fragmentos de coroa e muralha abaxial dos dígitos foram colhidos para histologia 30 horas após a indução. Foram identificados sinais de acidose ruminal e metabólica como distensão ruminal com líquido, diarreia e baixo pH ruminal. Os resultados de hemogasometria indicaram baixos pH e nível plasmático de bicarbonato. Os animais não apresentaram claudicação, entretanto, observaram-se apatia e marcha mais lenta, atribuídas à acidose metabólica. Histologicamente foram observadas lesões indicativas de laminite como alterações circulatórias e infiltrado inflamatório na derme, irregularidades e áreas de destacamento da membrana basal e alterações morfológicas de células da epiderme basal. O protocolo induziu, nas primeiras 30 horas, sinais de acidose ruminal e metabólica e lesões histológicas de baixa intensidade nos dígitos. Não foi observada claudicação ou sensibilidade nos dígitos, caracterizando a fase prodrômica da enfermidade.(AU)