N-acetylcysteine modulates redox imbalance and inflammation in macrophages and mice exposed to formaldehyde

Abstract

This study aimed to evaluate the protective role of N-acetylcysteine (NAC) in cells and mice exposed to formaldehyde. For the in vitro study, J774A.1 macrophages cells were incubated for 8, 16 and 24 h with formaldehyde or NAC to assess cell viability and reactive oxygen species (ROS). In the in vivo study, C57BL/6 mice (n = 48) were divided into 6 groups: control (CG), vehicle (VG) that received saline by orogastric gavage, a group exposed to formaldehyde 1% (FG) and formaldehyde exposed groups that received NAC at doses of 100, 150 and 200 mg/Kg (FN100, FN150 and FN200) for a period of 5 days. In vitro, formaldehyde promoted a decrease in cell viability and increased ROS, while NAC reduced formaldehyde-induced ROS production. Animals exposed to formaldehyde presented higher leukocyte counts in the blood and in the bronchoalveolar lavage fluid, and promoted secretion of inflammatory markers IL-6, IL-15, and IL-10. The exposure to formaldehyde also promoted redox imbalance and oxidative damage characterized by increased activities of superoxide dismutase, catalase, decreased GSH/GSSG ratio, as well as it increased levels of protein carbonyls and lipid peroxidation. NAC administration after formaldehyde exposure attenuated oxidative stress markers, secretion of inflammatory mediators and lung inflammation. In conclusion, both in in vitro and in vivo models, NAC administration exerted protective effects, which modulated the inflammatory response and redox imbalance, thus preventing the development airway injury induced by formaldehyde exposure.

Keywords:

• N-acetylcysteine
• formaldehyde
• oxidative stress
• inflammation
• lung

Acknowledgments

The authors thank Michel Oliveira and Yannick Diedrich for their technical assistance during this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors are thankful to Financiadora de Estudos e Projetos (Study and Project Financing Institution) – FINEP; Fundação de Amparo à Pesquisa de Minas (Foundation for Research Support of Minas Gerais) (FAPEMIG) [FAPEMIG – n° APQ − 02511-22] and Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development (CNPq) [CNPq – n° 305385/2021-6, nº 305634/2017-8].