Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
Vet Microbiol. 2012 Apr 23;156(1-2):222-6. doi: 10.1016/j.vetmic.2011.10.008. Epub 2011 Oct 15.
This study evaluated the in vitro activity of diphenyl diselenide against 19 Pythium insidiosum isolates and the in vivo therapeutic response of rabbits with experimentally induced pythiosis. In vitro: susceptibility tests were performed using the broth macrodilution method in accordance with the CLSI document M38-A2. The criteria for interpretation were as follows: MIC-1 and MIC-2 (inhibition of 90% and 100% of mycelium growth, respectively) and the minimum fungicide concentration (MIC-3). In vivo: twenty rabbits were divided into four groups with five animals each and treated for 40 consecutive days: groups 1 and 2 (experimentally induced pythiosis) were treated with diphenyl diselenide (10mg/kg/day) and canola oil (1 mL/kg/day), respectively; groups 3 and 4 (controls) were treated with canola oil (1 mL/kg/day) and diphenyl diselenide (10mg/kg/day), respectively. Toxicity was evaluated using biochemical and haematological parameters. In vitro susceptibility tests showed that 89.4% of isolates had a MIC-1 ≤ 0.5 μg/mL, 84.2% of isolates had a MIC-2 ≤ 1.0 μg/mL and 94.7% of isolates had a MIC-3 ≤ 2.0 μg/mL. The in vivo assay suggested that this compound has a fungistatic activity, and the biochemical and haematological parameters indicated that there was no renal, hepatic or haematological toxicity. The comparison of the unsaturated iron binding capacity levels between animals with and without pythiosis suggested the involvement of iron metabolism in the pathogenesis of pythiosis. This study demonstrated the absence of detectable toxicity caused by diphenyl diselenide and the in vitro fungicidal and in vivo fungistatic activities of this drug, which makes it an option for future therapeutic approaches in the treatment of pythiosis.
本研究评估了二苯基二硒对 19 株嗜热丝孢霉分离株的体外活性和实验诱导的嗜热丝孢霉病兔的体内治疗反应。体外：采用肉汤微量稀释法按照 CLSI 文件 M38-A2 进行药敏试验。解释标准如下：MIC-1 和 MIC-2（分别抑制 90%和 100%菌丝生长）和最低杀真菌浓度（MIC-3）。体内：20 只兔子分为 4 组，每组 5 只，连续治疗 40 天：第 1 组和第 2 组（实验性嗜热丝孢霉病）分别用二苯基二硒（10mg/kg/天）和菜籽油（1ml/kg/天）治疗；第 3 组和第 4 组（对照组）分别用菜籽油（1ml/kg/天）和二苯基二硒（10mg/kg/天）治疗。使用生化和血液学参数评估毒性。体外药敏试验表明，89.4%的分离株 MIC-1≤0.5μg/ml，84.2%的分离株 MIC-2≤1.0μg/ml，94.7%的分离株 MIC-3≤2.0μg/ml。体内试验表明，该化合物具有抑菌活性，生化和血液学参数表明无肾、肝或血液毒性。有和无嗜热丝孢霉病动物的未饱和铁结合能力水平比较表明，铁代谢参与了嗜热丝孢霉病的发病机制。本研究表明二苯基二硒无明显毒性，体外杀菌和体内抑菌活性，为未来治疗嗜热丝孢霉病提供了一种选择。
