PMID- 31578565
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20210125
IS  - 1460-2709 (Electronic)
IS  - 1369-3786 (Linking)
VI  - 58
IP  - 5
DP  - 2020 Jul 1
TI  - Evaluation of antifibrotic and antifungal combined therapies in experimental 
      pulmonary paracoccidioidomycosis.
PG  - 667-678
LID - 10.1093/mmy/myz100 [doi]
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides 
      genus. Most of the patients with chronic form present sequelae, like pulmonary 
      fibrosis, with no effective treatment, leading to impaired lung functions. In the 
      present study, we aimed to investigate the antifibrotic activity of three 
      compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a 
      murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole 
      (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal 
      route and after 8 weeks, they were submitted to one of the following six 
      treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 
      weeks of treatment, the lungs were collected for determination of fungal burden, 
      production of OH-proline, deposition of reticulin fibers, and pulmonary 
      concentrations of cytokines and growth factors. Pb-infected mice treated with 
      PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, 
      associated with lower concentrations of interleukin (IL)-6, IL-17, and 
      transforming growth factor (TGF)-beta1 and higher concentrations of IL-10 compared 
      to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased 
      pulmonary concentrations of OH-proline associated with lower levels of TGF-beta1, 
      and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and 
      CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, 
      high pulmonary concentrations of CCL3, IFN-gamma and VEGF, and decreased 
      concentrations of IL-6, IL-1beta, IL-17, and TGF-beta1. In conclusion, our findings 
      reinforce the antifibrotic role of PTX only when associated with ITC, and AZT 
      only when associated with CMX, but Thal did not show any action upon addition.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of The 
      International Society for Human and Animal Mycology.
FAU - Finato, Angela C
AU  - Finato AC
AD  - Faculdade de Ciencias. Universidade Estadual Paulista (UNESP), 17033-360 Bauru, 
      SP, Brazil.
FAU - Almeida, Debora F
AU  - Almeida DF
AD  - Faculdade de Ciencias. Universidade Estadual Paulista (UNESP), 17033-360 Bauru, 
      SP, Brazil.
AD  - Faculdade de Medicina (FAMED). Universidade Federal do Mato Grosso do Sul (UFMS). 
      79070-900 Campo Grande, MS, Brazil.
FAU - Dos Santos, Amanda R
AU  - Dos Santos AR
AD  - Faculdade de Ciencias. Universidade Estadual Paulista (UNESP), 17033-360 Bauru, 
      SP, Brazil.
AD  - Faculdade de Medicina (FAMED). Universidade Federal do Mato Grosso do Sul (UFMS). 
      79070-900 Campo Grande, MS, Brazil.
FAU - Nascimento, Dejair C
AU  - Nascimento DC
AD  - Instituto Lauro de Souza Lima (ILSL), 17034-971 Bauru, SP, Brazil.
FAU - Cavalcante, Ricardo S
AU  - Cavalcante RS
AD  - Faculdade de Medicina de Botucatu. Universidade Estadual Paulista (UNESP), 
      18618-687 Botucatu, SP, Brazil.
FAU - Mendes, Rinaldo P
AU  - Mendes RP
AD  - Faculdade de Medicina (FAMED). Universidade Federal do Mato Grosso do Sul (UFMS). 
      79070-900 Campo Grande, MS, Brazil.
AD  - Faculdade de Medicina de Botucatu. Universidade Estadual Paulista (UNESP), 
      18618-687 Botucatu, SP, Brazil.
FAU - Soares, Cleverson T
AU  - Soares CT
AD  - Instituto Lauro de Souza Lima (ILSL), 17034-971 Bauru, SP, Brazil.
FAU - Paniago, Anamaria M M
AU  - Paniago AMM
AD  - Faculdade de Medicina (FAMED). Universidade Federal do Mato Grosso do Sul (UFMS). 
      79070-900 Campo Grande, MS, Brazil.
FAU - Venturini, James
AU  - Venturini J
AD  - Faculdade de Medicina (FAMED). Universidade Federal do Mato Grosso do Sul (UFMS). 
      79070-900 Campo Grande, MS, Brazil.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Med Mycol
JT  - Medical mycology
JID - 9815835
RN  - 0 (Antifungal Agents)
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 304NUG5GF4 (Itraconazole)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
RN  - 83905-01-5 (Azithromycin)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Animals
MH  - Antifungal Agents/*administration & dosage
MH  - Azithromycin/administration & dosage
MH  - Cytokines/analysis
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Immunosuppressive Agents/administration & dosage
MH  - Intercellular Signaling Peptides and Proteins/analysis
MH  - Itraconazole/administration & dosage
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Paracoccidioides/*drug effects/growth & development
MH  - Paracoccidioidomycosis/*drug therapy/microbiology/pathology
MH  - Pentoxifylline/administration & dosage
MH  - Pulmonary Fibrosis/*drug therapy
MH  - Random Allocation
MH  - Thalidomide/administration & dosage
MH  - Treatment Outcome
MH  - Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage
OTO - NOTNLM
OT  - Paracoccidioides brasiliensis
OT  - azithromycin
OT  - cotrimoxazole
OT  - itraconazole
OT  - pentoxifylline
OT  - pulmonary fibrosis
OT  - thalidomide
EDAT- 2019/10/04 06:00
MHDA- 2021/01/26 06:00
CRDT- 2019/10/04 06:00
PHST- 2019/05/02 00:00 [received]
PHST- 2019/08/27 00:00 [revised]
PHST- 2019/09/11 00:00 [accepted]
PHST- 2019/10/04 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
PHST- 2019/10/04 06:00 [entrez]
AID - 5580272 [pii]
AID - 10.1093/mmy/myz100 [doi]
PST - ppublish
SO  - Med Mycol. 2020 Jul 1;58(5):667-678. doi: 10.1093/mmy/myz100.