da Costa Bárbara, Pippi Bruna, Berlitz Simone Jacobus, Carvalho Anderson Ramos, Teixeira Mario Lettieri, Külkamp-Guerreiro Irene Clemes, Andrade Saulo F, Fuentefria Alexandre Meneghello
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Mycoses. 2021 Jul;64(7):727-733. doi: 10.1111/myc.13276. Epub 2021 Apr 4.
Dermatophytosis is a superficial fungal infection that affects humans and is very common in small animals. The treatment using the most commonly used antifungals is failing, and new therapeutic alternatives are required to combat the resistance of these fungal infections. Previous studies by the group have shown that clioquinol is an important therapeutic alternative in the treatment of dermatophytosis. The object was to conduct studies of antidermatophytic activity and the irritant potential from the double and triple combinations of clioquinol, terbinafine and ciclopirox in ex vivo and in vivo alternative models. To evaluate the irritant potential of antifungal combinations, the alternative HET-CAM method (chicken egg test chorioallantoic membrane) was used. Ex vivo models were used to assess the effectiveness of antifungal combinations, using pig hooves and veterinary fur. Any possible tissue damage was to assess through in histopathology of swine ears. HET-CAM results showed that all combinations can be classified as non-irritating, corroborated by the results of the histopathological evaluation of the pig's ear skin. Only the double combinations managed to remove 100% of the colony-forming units (CFU) formed on the pig's hooves. The clioquinol + terbinafine combination and the triple combination were more effective than clioquinol + ciclopirox in eradicating the preformed biofilm in fur of veterinary origin. These results show the potential of formulations of clioquinol in combination with antifungals for use in humans and in the veterinary field to combat dermatophytosis, as an important alternative therapy, for use in the near future.
皮肤癣菌病是一种影响人类的浅表真菌感染，在小动物中也很常见。使用最常用的抗真菌药物进行治疗正逐渐失效，因此需要新的治疗方法来对抗这些真菌感染的耐药性。该研究小组之前的研究表明，氯碘羟喹是治疗皮肤癣菌病的一种重要治疗方法。目的是在体外和体内替代模型中，对氯碘羟喹、特比萘芬和环吡酮的双重和三重组合进行抗皮肤癣菌活性和刺激潜力的研究。为了评估抗真菌组合的刺激潜力，使用了替代的HET-CAM方法（鸡胚绒毛尿囊膜试验）。使用猪蹄和兽用皮毛的体外模型来评估抗真菌组合的有效性。通过猪耳的组织病理学评估来评估任何可能的组织损伤。HET-CAM结果表明，所有组合均可归类为无刺激性，猪耳皮肤的组织病理学评估结果证实了这一点。只有双重组合成功去除了猪蹄上形成的100%的菌落形成单位（CFU）。氯碘羟喹 + 特比萘芬组合和三重组合在消除兽用皮毛中预先形成的生物膜方面比氯碘羟喹 + 环吡酮更有效。这些结果表明，氯碘羟喹与抗真菌药物联合制剂在人类和兽医领域对抗皮肤癣菌病具有潜力，作为一种重要的替代疗法，可在不久的将来使用。
