Involvement of ERK and Oxidative Stress in Airway Exposure to Cadmium Chloride Aggravates Airway Inflammation in Ovalbumin-Induced Asthmatic Mice

Chendong Wu; Xinyue Hu; Yuanyuan Jiang; Jiale Tang; Huan Ge; Shuanglinzi Deng; Xiaozhao Li; Juntao Feng

doi:10.3390/toxics12040235

Involvement of ERK and Oxidative Stress in Airway Exposure to Cadmium Chloride Aggravates Airway Inflammation in Ovalbumin-Induced Asthmatic Mice

Toxics. 2024 Mar 23;12(4):235. doi: 10.3390/toxics12040235.

Authors

Chendong Wu^{1

2}, Xinyue Hu^{1

2}, Yuanyuan Jiang^{1

2}, Jiale Tang^{1

2}, Huan Ge^{1

2}, Shuanglinzi Deng^{1

2}, Xiaozhao Li^{2

3}, Juntao Feng^{1

2}

Affiliations

¹ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha 410005, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410005, China.
³ Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410005, China.

Abstract

Inhalation represents a significant route of cadmium (Cd) exposure, which is associated with an elevated risk of lung diseases. This research study aims to evaluate the impact of repeated low-dose cadmium inhalation on exacerbating airway inflammation induced by ovalbumin (OVA) in asthma-afflicted mice. Mice were grouped into four categories: control (Ctrl), OVA, cadmium chloride (CdCl₂), and OVA + cadmium chloride (OVA + CdCl₂). Mice in the OVA group displayed increased airway mucus secretion and peribronchial and airway inflammation characterized by eosinophil cell infiltration, along with elevated levels of Th2 cytokines (IL-4, IL-5, IL-13) in bronchoalveolar lavage fluids (BALFs). These parameters were further exacerbated in the OVA + CdCl₂ group. Additionally, the OVA + CdCl₂ group exhibited higher levels of the oxidative stress marker malondialdehyde (MDA), greater activity of glutathione peroxidase (GSH-Px), and higher phosphorylation of extracellular regulated kinase (ERK) in lung tissue. Treatment with U0126 (an ERK inhibitor) and α-tocopherol (an antioxidant) in the OVA + CdCl₂ group resulted in reduced peribronchial and airway inflammation as well as decreased airway mucus secretion. These findings indicate that CdCl₂ exacerbates airway inflammation in OVA-induced allergic asthma mice following airway exposure. ERK and oxidative stress are integral to this process, and the inhibition of these pathways significantly alleviates the adverse effects of CdCl₂ on asthma exacerbation.

Keywords: ERK; asthma; cadmium; oxidative stress; α-tocopherol.

Abstract

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