PMID- 21437728
OWN - NLM
STAT- MEDLINE
DCOM- 20111107
LR  - 20211020
IS  - 1573-0832 (Electronic)
IS  - 0301-486X (Linking)
VI  - 172
IP  - 2
DP  - 2011 Aug
TI  - Experimental chemotherapy in paracoccidioidomycosis using ruthenium NO donor.
PG  - 95-107
LID - 10.1007/s11046-011-9416-8 [doi]
AB  - Paracoccidioidomycosis (PCM) is a granulomatous disease caused by a dimorphic 
      fungus, Paracoccidioides brasiliensis (Pb). To determine the influence of nitric 
      oxide (NO) on this disease, we tested cis-[Ru(bpy)2(NO)SO3](PF6), ruthenium 
      nitrosyl, which releases NO when activated by biological reducing agents, in 
      BALB/c mice infected intravenously with Pb 18 isolate. In a previous study by our 
      group, the fungicidal activity of ruthenium nitrosyl was evaluated in a mouse 
      model of acute PCM, by measuring the immune cellular response (DTH), 
      histopathological characteristics of the granulomatous lesions (and numbers), 
      cytokines, and NO production. We found that cis-[Ru(bpy)2(NO)SO3](PF6)-treated 
      mice were more resistant to infection, since they exhibited higher survival when 
      compared with the control group. Furthermore, we observed a decreased influx of 
      inflammatory cells in the lung and liver tissue of treated mice, possibly because 
      of a minor reduction in fungal cell numbers. Moreover, an increased production of 
      IL-10 and a decrease in TNF-alpha levels were detected in lung tissues of infected 
      mice treated with cis-[Ru(bpy)2(NO)SO3](PF6). Immunohistochemistry showed that 
      there was no difference in the number of VEGF- expressing cells. The animals 
      treated with cis-[Ru(bpy)2(NO)SO3](PF6) showed high NO levels at 40 days after 
      infection. These results show that NO is effectively involved in the mechanism 
      that regulates the immune response in lung of Pb-infected mice. These data 
      suggest that NO is a resistance factor during paracoccidioidomycosis by 
      controlling fungal proliferation, influencing cytokine production, and 
      consequently moderating the development of a strong inflammatory response.
FAU - Pavanelli, Wander Rogerio
AU  - Pavanelli WR
AD  - Department of Pathology Science, CCB, State University of Londrina-UEL, Londrina, 
      PR, Brazil. wanderpavanelli@uel.br
FAU - da Silva, Jean Jerley Nogueira
AU  - da Silva JJ
FAU - Panis, Carolina
AU  - Panis C
FAU - Cunha, Thiago Mattar
AU  - Cunha TM
FAU - Costa, Ivete Conchon
AU  - Costa IC
FAU - de Menezes, Maria Claudia Noronha Dutra
AU  - de Menezes MC
FAU - Oliveira, Francisco Jose de Abreu
AU  - Oliveira FJ
FAU - Lopes, Luiz Gonzaga de Franca
AU  - Lopes LG
FAU - Cecchini, Rubens
AU  - Cecchini R
FAU - Cunha, Fernando de Queiroz
AU  - Cunha Fde Q
FAU - Watanabe, Maria Angelica Ehara
AU  - Watanabe MA
FAU - Itano, Eiko Nakagawa
AU  - Itano EN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110325
PL  - Netherlands
TA  - Mycopathologia
JT  - Mycopathologia
JID - 7505689
RN  - 0 (Antifungal Agents)
RN  - 0 (Ruthenium Compounds)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Antifungal Agents/*administration & dosage
MH  - Colony Count, Microbial
MH  - Disease Models, Animal
MH  - Female
MH  - Histocytochemistry
MH  - Lung/microbiology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nitric Oxide/*administration & dosage
MH  - Paracoccidioides/drug effects/isolation & purification
MH  - Paracoccidioidomycosis/*drug therapy/pathology
MH  - Rodent Diseases/drug therapy
MH  - Ruthenium Compounds/*administration & dosage
MH  - Survival Analysis
MH  - Treatment Outcome
EDAT- 2011/03/26 06:00
MHDA- 2011/11/08 06:00
CRDT- 2011/03/26 06:00
PHST- 2010/09/14 00:00 [received]
PHST- 2011/03/06 00:00 [accepted]
PHST- 2011/03/26 06:00 [entrez]
PHST- 2011/03/26 06:00 [pubmed]
PHST- 2011/11/08 06:00 [medline]
AID - 10.1007/s11046-011-9416-8 [doi]
PST - ppublish
SO  - Mycopathologia. 2011 Aug;172(2):95-107. doi: 10.1007/s11046-011-9416-8. Epub 2011 
      Mar 25.