Avaliação da exposição in vivo ao formaldeído sobre parâmetros do estresse oxidativo, inflamação e modificações epigenéticas

Abstract

Air quality has been discussed for some time among the scientific community. Air pollution in the external environment and that of the indoor environment have been caused for concern. Volatile organic compounds (VOCs) are the pollutants that most contribute to inadequate indoor air quality. Formaldehyde (FA) is the VOC with the highest emission indoors and is found in industrial environments, building materials and consumer products such as cosmetics, detergents and disinfectants. Exposure to FA has been related to several toxic effects. Studies have shown associations between exposure to FA and clinical symptoms such as eye and upper respiratory tract irritation, immunological changes, and mutagenic changes. In this context, this study aimed to evaluate for 28 days the FA 5 ppm inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage (BAL) was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. In addition, the possible protective effect of melatonin 20 mg/kg against exposure to FA was evaluated in modulating the damage induced by exposure, since the effects of melatonin are related to its antioxidant activity, thus being able to play a bioprotective effect. The experimental in vivo results showed that FA induces a significant increase in TBARS (p<0.05) and NO (p<0.05) levels and a decrease in NPSH levels (p<0.01). In addition, there were observed increases in inflammatory cells recruited for BAL and remodeling of the lung parenchyma, evidenced by histology analysis. These findings possibly characterize oxidative and inflammatory damage to the lung. Likewise, in the liver tissue, the exposure to 5 ppm FA increased TBARS (p<0.0001) and PCO (p<0.05) levels and decreased NPSH levels. Besides, FA significantly induced DNA damage, evidenced by the increase of % tail moment (p<0.01) and MN frequency (p<0.05). The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial melatonin role. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.