Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis

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 antifibr...

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Bibliographic Details
Published in:Journal of fungi (Basel) 2022-09, Vol.8 (10), p.1010
Main Authors: 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
Format: Article
Language:English
Subjects:
Cell culture
Collagen
Complications
Cotrimoxazole
Cytokines
Fibers
Fibronectin
Fibrosis
Flavonoids
Fungi
Gelatinase A
Gelatinase B
Herbal medicine
Hydroxyproline
Immune response
Immunomodulation
Infections
Lung diseases
Lungs
Membranes
Mycosis
paracoccidioidomycosis
Proteins
Pulmonary fibrosis
pulmonary sequelae
Quality of life
Silymarin
South American blastomycosis
Spleen
Tissue inhibitor of metalloproteinase 2
Trachea
Transforming growth factor-b1
Variance analysis
γ-Interferon
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Summary: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.
ISSN:2309-608X
2309-608X
DOI:10.3390/jof8101010