The putative role of ovary removal and progesterone when considering the effect of formaldehyde exposure on lung inflammation induced by ovalbumin.
OBJECTIVE
Formaldehyde exposure during the menstrual cycle is known to affect the course of allergic lung inflammation. Because our previous data demonstrated that formaldehyde combined with an ovariectomy reduced allergic lung inflammation, we investigated the putative role of ovary removal and progesterone treatment when considering the effect of formaldehyde on allergic lung inflammation.


METHODS
Ovariectomized rats and their matched controls were exposed to formaldehyde (1%, 3 days, 90 min/day) or vehicle, and immediately after exposure, the rats were sensitized to ovalbumin by a subcutaneous route. After 1 week, the rats received a booster by the same route, and after an additional week, the rats were challenged with ovalbumin (1%) by an aerosol route. The leukocyte numbers, interleukin-10 (IL-10) release, myeloperoxidase activity, vascular permeability, ex vivo tracheal reactivity to methacholine and mast cell degranulation were determined 24 h later.


RESULTS
Our results showed that previous exposure to formaldehyde in allergic rats decreased lung cell recruitment, tracheal reactivity, myeloperoxidase activity, vascular permeability and mast cell degranulation while increasing IL-10 levels. Ovariectomy only caused an additional reduction in tracheal reactivity without changing the other parameters studied. Progesterone treatment reversed the effects of formaldehyde exposure on ex vivo tracheal reactivity, cell influx into the lungs and mast cell degranulation.


CONCLUSIONS
In conclusion, our study revealed that formaldehyde and ovariectomy downregulated allergic lung inflammation by IL-10 release and mast cell degranulation. Progesterone treatment increased eosinophil recruitment and mast cell degranulation, which in turn may be responsible for tracheal hyperreactivity and allergic lung inflammation.
Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São PauloSP, Brazil.
Adriana
A
Lino-dos-Santos-Franco
Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São PauloSP, Brazil.
Renata Midori
RM
Amemiya
Department of Biophotonics, Nove de Julho University, São PauloSP, Brazil.
Ana Paula Ligeiro de
AP
Oliveira
Department of Basic Science in Health, Faculty of Medical Sciences, Universidade de Cuiabá, CuiabaMT, Brazil.
Amílcar Sabino
AS
Damazo
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São PauloSP, Brazil.
Ana Cristina
AC
Breithaupt-Faloppa
Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São PauloSP, Brazil.
Luana Beatriz
LB
Vitoretti
Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São PauloSP, Brazil.
Beatriz Golegã
BG
Acceturi
Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São PauloSP, Brazil.
Wothan
W
Tavares-de-Lima
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005557:Formaldehyde / Q000009:adverse effects*; D016753:Interleukin-10 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects; D010047:Ovalbumin / Q000009:adverse effects*; D010052:Ovariectomy; D009195:Peroxidase / Q000032:analysis / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced*; D011374:Progesterone / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012130:Respiratory Hypersensitivity; D013997:Time Factors
D016753:Interleukin-10; D005557:Formaldehyde; D011374:Progesterone; D010047:Ovalbumin; D009195:Peroxidase