Resende Victor Quinholes, Reis-Goes Karoline Hagata, Finato Angela Carolina, de Fátima Almeida-Donanzam Débora, Dos Santos Amanda Ribeiro, Perico Jonatas, Amorim Barbara Casella, Venturini James
Faculdade de Ciências, Universidade Estadual Paulista (UNESP), Bauru 17033-360, SP, Brazil.
Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu 18618-970, SP, Brazil.
J Fungi (Basel). 2022 Sep 27;8(10):1010. doi: 10.3390/jof8101010.
Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB/c mice infected with P. brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, α-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-β1 and fibronectin and high levels of MMP-2 and IFN-γ were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response.
副球孢子菌病（PCM）主要影响农村工人，是一种由副球孢子菌属引起的系统性真菌病，在大多数成年患者中会引发肺部后遗症，导致严重残疾并损害其生活质量。水飞蓟素是一种具有有效抗纤维化活性的草药。考虑到在PCM中，肺纤维化尚无抗纤维化治疗方法，我们旨在评估通过气管内途径给予水飞蓟素和复方新诺明（CMX）联合治疗对感染巴西副球孢子菌酵母的BALB/c小鼠的效果。治疗12周后，收集肺部以测定真菌负荷、羟脯氨酸的产生、胶原纤维的沉积、肺组织中细胞因子的浓度以及纤连蛋白、α-平滑肌肌动蛋白（α-SMA）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制剂-2（TIMP-2）的表达。还进行了脾细胞培养。我们的结果表明，与安慰剂组相比，接受水飞蓟素/CMX联合治疗的感染小鼠肺部胶原纤维沉积减少，肺组织中羟脯氨酸浓度降低。在这组小鼠中还观察到转化生长因子-β1（TGF-β1）和纤连蛋白水平降低，以及MMP-2和干扰素-γ（IFN-γ）水平升高。总的来说，我们的研究结果表明，抗真菌治疗与水飞蓟素联合使用具有强大的抗纤维化作用，并伴有免疫调节作用，可增强抗真菌免疫反应。
