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Selenium Deficiency Caused Fibrosis as an Oxidative Stress-induced Inflammatory Injury in the Lungs of Mice

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Abstract

Selenium (Se) is a vital trace element in the regulation of inflammation and antioxidant reactions in both animals and humans. Se deficiency is rapidly affecting lung function. The present study investigated the molecular mechanism of Se deficiency aggravates reactive oxygen species (ROS)-induced inflammation, leading to fibrosis in lung. Mice fed with different concentrations of Se to establish the model. In the Se-deficient group, the ROS and malondialdehyde (MDA) was increased, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) reduced. The histopathological observation showed that Se deficiency lead to lung texture damage with varying degrees of degeneration, necrosis, shedding of some alveolar epithelial cells, and inflammatory cell infiltration. Immunohistochemistry showed that the expression of α-smooth muscle actin (α-SMA) increased. The fibrosis index was verified with Sirius red staining. The ELISA and qPCR results showed that the inflammatory cytokines (TNF-α and IL-1β) and ECM (collagen I, collagen IV, fibronectin, and laminin) were increased with ROS increasing, which was induced by Se deficiency. The results displayed that oxidative stress with Se deficiency led to an increase in tissue inhibitors of metalloproteinase (TIMPs), but a decrease in matrix metalloproteinases (MMPs). All the results indicated that Se deficiency induced excessive ROS accumulation to generate inflammation, which disrupted ECM homeostasis and aggravated fibrosis in the lung.

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The data of this study will be made available on reasonable request.

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Contributions

Meng-yao Guo and Yu-xin Fu conceived and designed the experiments. Yu-xin Fu, Yi-bo Wang, and Qing-wei Bu carried out the experiments. Yu-xin Fu and Yi-bo Wang processed the data. Yu-xin Fu and Meng-yao Guo wrote the paper. The manuscript was approved by all the authors.

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Correspondence to Meng-yao Guo.

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All the animal experiments involved in this paper have been approved by the Animal Research Ethics Committee of Northeast Agricultural University (NAUMO-2021–0219).

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The authors declare no competing interests.

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Fu, Yx., Wang, Yb., Bu, Qw. et al. Selenium Deficiency Caused Fibrosis as an Oxidative Stress-induced Inflammatory Injury in the Lungs of Mice. Biol Trace Elem Res 201, 1286–1300 (2023). https://doi.org/10.1007/s12011-022-03222-6

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