Vitamin C rescues in part the effects of nitrofen on cultured human pneumocytes.
BACKGROUND
One of the mechanisms of action of nitrofen is intracellular oxidative stress. It is therefore likely that anti-oxidant agents can counteract its action. The aim of this study was to examine whether vitamin C mitigates the effects of nitrofen on the proliferation/apoptosis balance and functional maturation of cultured human pneumocytes.


METHODS
Lung aCa type II pneumocytes (NIH-H441) in culture were exposed to 1.5 microM of nitrofen alone or followed 48 h later by 60 microM of vitamin C. The culture dishes were recovered at 72 h for immunohistochemical (PCNA for proliferation, bis-benzimide for apoptosis, anti-SpB and anti-TTF-1 antibodies for SpB and TTF-1 assessment) and molecular studies. Real-time PCR was used to quantitate TTF-1 RNAm, with S26 as internal control. ANOVA or Kruskall-Wallis with appropriate post hoc tests were used for comparison with p<0.05 as threshold of significance.


RESULTS
Nitrofen decreased proliferation and TTF/1 and SpB expression with no apparent affect on apoptosis. Additional exposure to vitamin C reverted these effects. Furthermore, nitrofen decreased TTF/1 mRNA and vitamin C tended to rescue normal values.


CONCLUSIONS
Vitamin C partially rescued proliferation and maturity in nitrofen-treated human pneumocytes. The likely beneficial influence of this prenatal anti-oxidant medication should be further investigated.
González-Reyes
Salomé
S
Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
Martínez
Leopoldo
L
Tovar
Juan A
JA
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010647:Phenyl Ethers / Q000494:pharmacology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis / Q000187:drug effects; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects
D000975:Antioxidants; D006540:Herbicides; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D016877:Oxidants; D010647:Phenyl Ethers; D037701:Pulmonary Surfactant-Associated Protein B; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C007350:nitrofen; D001205:Ascorbic Acid