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Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and
1Department of Respiratory Medicine, Hebei General Hospital, Shijiazhuang, 050051 China.
Abstract:
Objective To evaluate the antagonistic effects of N-acetylcysteine (NAC) on mitogen-activated protein kinases (MAPK) pathway activation, oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter (PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups: blank control group (C1), water drip control group (C2), PM2.5 exposed group (P), low-dose NAC treated and PM2.5 exposed group (L), middle-dose NAC treated and PM2.5 exposed group (M), and high-dose NAC treated and PM2.5 exposed group (H). PM2.5 suspension (7.5 mg/kg) was administered tracheally once a week for four times. NAC of 125 mg/kg, 250 mg/kg and 500 mg/kg was delivered intragastrically to L, M and H group respectively by gavage (10 ml/kg) for six days before PM2.5 exposure. The histopathological changes and human mucin 5 subtype AC (MUC5AC) content in lung tissue of rats were evaluated. We investigated IL-6 in serum and bronchoalveolar lavage fluid (BALF) by Enzyme-linked immunosorbent assay (ELISA), MUC5AC in lung tissue homogenate by ELISA, glutathione peroxidase (GSH-PX) in serum and BALF by spectrophotometry, and the expression of p-ERK1/2, p-JNK1/2 and p-p38 proteins by Western blot. All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells. Rats receiving NAC treatment showed less histological destruction and mucus secretion. Of P, L, M and H group, MUC5AC in lung tissue, IL-6 in serum and BALF were higher than controls (C1 and C2) (all P<0.05), with the highest levels found in the P group and a decreasing trend with increase of NAC dose. The activity of GSH-PX in serum and BALF of PM2.5 exposed rats (P, L, M and H) was lower than that of controls (all P<0.05), with higher activities found in NAC treated rats (L, M, and H), and an increasing trend with increase of NAC dose. The expressions of p-ERK1/2, p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue (P, L, M and H) was higher than controls (all P<0.05), with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation, lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
Insights
N-acetylcysteine (NAC) effectively counteracts lung injury, oxidative stress, and inflammation caused by fine particulate matter (PM2.5) exposure in rats. NAC treatment reduced inflammatory markers and MAPK pathway activation, demonstrating its protective role.
Area of Science:
- Environmental Health
- Toxicology
- Pulmonary Medicine
Background:
- Fine particulate matter (PM2.5) exposure is a significant environmental risk factor linked to respiratory diseases.
- PM2.5 inhalation can induce oxidative stress, inflammation, and lung tissue damage.
- Mitogen-activated protein kinases (MAPK) pathways are implicated in the cellular response to PM2.5.
Purpose of the Study:
- To investigate the protective effects of N-acetylcysteine (NAC) against PM2.5-induced lung injury.
- To evaluate NAC's impact on MAPK pathway activation, oxidative stress, and inflammation in a rat model.
- To determine the dose-dependent efficacy of NAC in mitigating PM2.5 toxicity.
Main Methods:
- Wistar rats were exposed to PM2.5 and treated with varying doses of NAC.
- Histopathological examination of lung tissue and measurement of MUC5AC content were performed.
- Serum and bronchoalveolar lavage fluid (BALF) were analyzed for IL-6 and glutathione peroxidase (GSH-PX) levels.
- Western blot was used to assess the expression of phosphorylated MAPK proteins (p-ERK1/2, p-JNK1/2, p-p38).
Main Results:
- PM2.5 exposure led to lung tissue destruction and increased mucus secretion.
- NAC treatment attenuated histological damage and mucus production in a dose-dependent manner.
- NAC administration reduced elevated levels of IL-6 and MUC5AC, and increased GSH-PX activity.
- NAC downregulated the expression of p-ERK1/2, p-JNK1/2, and p-p38 proteins in lung tissue.
Conclusions:
- N-acetylcysteine (NAC) demonstrates significant antagonistic effects against PM2.5-induced lung injury.
- NAC mitigates PM2.5-induced oxidative stress and inflammatory responses.
- NAC effectively inhibits the activation of major MAPK pathways implicated in PM2.5 toxicity.
