N-acetylcysteine multifaceted activity in the control of toxicity induced in C57BL/6 mice by long-term inhalation of low-dose formaldehyde.

OBJECTIVE

This study investigated whether N-acetylcysteine (NAC) protects against the harmful effects induced by long-term inhalation of low-dose formaldehyde (FA).

MATERIALS AND

METHODS

Male C57BL/6 mice were divided into six groups: control (CG), vehicle (VG), FA-exposed (1% FA by inhalation), and three FA-exposed groups treated with NAC (100, 150, or 200 mg/kg; FN100, FN150, and FN200, respectively) administered by orogastric gavage during six months. Ventilatory and biometric parameters were assessed; biological samples were collected for analysis.

RESULTS

FA exposure reduced body mass and increased relative lung mass. Total and differential leukocyte counts in peripheral blood were reduced, whereas inflammatory cell influx to the airways was increased. Oxidative stress was evidenced by elevated carbonyl protein and TBARS levels. There was an increased superoxide dismutase activity, and reduced catalase activity. Redox imbalance was further characterized by increased sulfhydryl group levels, and there was a decreased reduced glutathione system. FA exposure also induced a marked inflammatory response, with elevated levels of IL-6, IL-15, IL-13, and IL-10. Structural lung damage was indicated by decreased alveolar airspace volume density and mean linear intercept, along with increased septal volume density, and it was associated with altered ventilatory parameters, including reduced respiratory rate and increased tidal volume. MMP-9 activity was reduced following FA exposure. NAC administration attenuated oxidative stress, inflammatory mediator release, pulmonary inflammation, and lung tissue damage.

CONCLUSION

These findings demonstrate that NAC exerts protective effects by modulating redox imbalance and inflammatory responses, thereby preventing lung injury and respiratory dysfunction induced by long-term FA inhalation.