Munhoz Lívia Silveira, Poester Vanice Rodrigues, Benelli Jéssica Louise, Melo Aryse Martins, Trápaga Mariana Rodrigues, Nogueira Cristina Wayne, Zeni Gilson, Flores Mariana Martins, Stevens David A, Xavier Melissa Orzechowski
Programa de Pós-graduação em Ciências da Saúde, Faculdade de Medicina (FAMED), Universidade Federal do Rio Grande (FURG), Rio Grande city, Rio Grande do Sul state, 96203-900, Brazil.
Universidade Federal de Santa Maria (UFSM), Santa Maria city, Rio Grande do Sul state, 97105-900, Brazil.
Med Mycol. 2023 Apr 3;61(4). doi: 10.1093/mmy/myad035.
Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (P < .001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.
二苯基二硒醚(PhSe)₂是一种稳定的有机硒化合物,对包括巴西孢子丝菌在内的多种真菌具有良好的体外抗真菌活性。该菌种与猫和人畜共患的孢子丝菌病有关,这是拉丁美洲一种新出现的真菌病。我们在小鼠模型中评估了(PhSe)₂单独使用以及与伊曲康唑联合使用对巴西孢子丝菌引起的孢子丝菌病的治疗效果。60只小鼠在足垫皮下感染巴西孢子丝菌,并连续30天通过灌胃进行治疗。六个治疗组分别接受:无活性治疗、伊曲康唑(50mg/kg)、剂量为1、5和10mg/kg的(PhSe)₂,或伊曲康唑(50mg/kg)+(PhSe)₂ 1mg/kg,接种后7天开始,每天一次。与未治疗组相比,单独使用1mg/kg的(PhSe)₂或伊曲康唑治疗的组中,内脏真菌负荷显著降低。(PhSe)₂的较高剂量(5和10mg/kg)增加了孢子丝菌病的临床表现和死亡率。伊曲康唑和1mg/kg的(PhSe)₂联合治疗优于它们单独的活性(P <.001)。这是首次证明(PhSe)₂单独使用或与目前的首选药物联合使用在治疗孢子丝菌病方面的潜在用途。