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. 2020 Nov 25;9(6):778-789.
doi: 10.1093/toxres/tfaa079. eCollection 2020 Dec.

Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin

Letícia Bernardini  1 , Eduardo Barbosa  2 , Mariele Feiffer Charão  2 , Gabriela Goethel  3 , Diana Muller  4 , Claiton Bau  4 , Nadine Arnold Steffens  5 , Carolina Santos Stein  5 , Rafael Noal Moresco  5 , Solange Cristina Garcia  3 , Marina Souza Vencato  6 , Natália Brucker  1
Affiliations

Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin

Letícia Bernardini et al. Toxicol Res (Camb). .

Abstract

Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA 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 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. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. 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 role of melatonin. 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.

Keywords: inflammation; oxidative damage; pollutant; toxicology; xenobiotic.

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Figures

Figure 1
Figure 1
Experimental design.
Figure 2
Figure 2
Level of lipid peroxidation in the liver of mice exposed to FA in different concentrations (n = 7). Data were expressed as mean ± SEM. aSignificant difference in relation to the control group (P < 0.0001).
Figure 3
Figure 3
Effect of FA and melatonin in BAL. (A) Inflammatory cells in BAL of mice. (B) NOx levels in BAL of mice. Values expressed as mean ± SEM. aSignificant difference in relation to the control group (P < 0.05); bSignificant difference in relation to Mel group (P < 0.05).
Figure 4
Figure 4
Effect of FA and melatonin in lung tissue. (A) TBARS levels. (B) Levels of non-protein thiols (NPSH). (C–F) Histology of control groups, Mel, 5 ppm and 5 ppm + Mel, respectively; 10x. Data expressed as mean ± SEM. aSignificant difference in comparison to the control group (P < 0.05); BR represents the bronchioles; IC represents inflammatory cells; AW represents the thickening of alveolar wall; AL represents the alveolar lumen.
Figure 5
Figure 5
Effect of FA and melatonin in plasma of mice. (A) AST activity. (B) ALT activity. (C) FRAP. Data were expressed as mean ± SEM. There were no significant differences among groups.
Figure 6
Figure 6
DNA damage. (A) Comet assay. (B) Micronucleus. (C) Global DNA methylation. Data were expressed as mean ± SEM. aSignificant difference in relation to the control group (P < 0.05); bSignificant difference in relation to Mel group (P < 0.05).
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