title: Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring.
abstract: Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150mg/kg, gavage) or vehicle (distilled water, gavage) 1h before FA exposure (0.92mg/m(3), 1h/day, 5days/week), for 21days, and the 30days old offspring were submitted to LPS injection (Salmonella abortus equi, 5mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Beatriz Silva
authors.initials: BS
authors.lastname: Ibrahim
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Éric Diego
authors.initials: ÉD
authors.lastname: Barioni
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Cíntia
authors.initials: C
authors.lastname: Heluany
authors.affiliation: Department of Immunology, University of São Paulo, São Paulo, Brazil.
authors.forename: Tárcio Teodoro
authors.initials: TT
authors.lastname: Braga
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Carine Cristiane
authors.initials: CC
authors.lastname: Drewes
authors.affiliation: Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil.
authors.forename: Silvia Goes
authors.initials: SG
authors.lastname: Costa
authors.affiliation: Department of Immunology, University of São Paulo, São Paulo, Brazil.
authors.forename: Niels Olsen Saraiva
authors.initials: NOS
authors.lastname: Câmara
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Sandra Helena Poliselli
authors.initials: SHP
authors.lastname: Farsky
authors.affiliation: Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil. Electronic address: alsantosfranco@gmail.com.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lino-Dos-Santos-Franco
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000187:drug effects; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D015870:Gene Expression; D007378:Interleukins / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013482:Superoxide Dismutase / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects; D000099156:Superoxide Dismutase 2
chemical_list: D001205:Ascorbic Acid; D051545:Cyclooxygenase 1; D005557:Formaldehyde; D007378:Interleukins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D051197:Toll-Like Receptor 4; D000099156:Superoxide Dismutase 2; C495347:Tlr4 protein, rat; C496318:Nos2 protein, rat; C496513:Ptgs1 protein, rat
keywords: Acute lung inflammation; Bone marrow; LPS; NF-kappa B; Oxidative stress; Toll-like receptor