Dexamethasone Blunts Lung Inflammation in Cholestatic Mice

Document Type : Original Article

Authors

1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

3 Food and Drug Administration, Iran Ministry of Health and Medical Education, Tehran, Iran

4 Department of Life Sciences, Shanxi Agricultural University, Shanxi, Taigu, China

5 Henan Key Laboratory of Environmental and Animal Product Safety College of Animal Science and Technology Henan University of Science and Technology Luoyang 471000 Henan, China

6 Students Research Committee, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

7 Biotechnology Incubator, Shiraz University of Medical Sciences, Shiraz, Iran

8 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Cholestasis/cirrhosis is a multifaceted clinical complication that influences many organs, including the liver, kidney, heart, skeletal muscle, and lung. Cirrhosis-associated lung injury could lead to severe and lethal consequences, including acute respiratory syndrome and patient dearth. Unfortunately, there is no specific pharmacological intervention to manage cholestasis-induced lung injury. It has been revealed that severe inflammation and its associated complications, such as oxidative stress, are involved in the pathogenesis of cholestasis-associated pulmonary damage. The current study was designed to evaluate the role of dexamethasone (DXM) on lung inflammation in cholestatic mice. For this purpose, bile duct ligated (BDL) mice received DXM (1 and 2.5 mg/kg, i.p, 2 times/week) for 14 days. On day 15, the bronchoalveolar lavage fluid (BALF) was prepared. Several markers, including inflammatory cell infiltration, TNF-α, and IgG, were assessed in the BALF of BDL animals. Significant infiltration of inflammatory cells along with increased TNF-α and IgG were detected in the BALF of BDL mice (14 days after surgery). Moreover, significant ROS formation, glutathione depletion, lipid peroxidation, and protein carbonylation were evident in the lung tissue of the BDL group. It was found that DXM (1 and 2.5 mg/kg) significantly blunted inflammation and oxidative stress in the lung of cholestatic mice. Moreover, lung tissue histopathological changes, including inflammatory cell infiltration, were significantly mitigated in DXM-treated mice. These data offer the potential therapeutic effects of DXM against cholestasis-related complications. Therefore, patients with cholestasis-induced lung injury might benefit from repurposing DXM in clinical settings.

Keywords

References

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Trends in Pharmaceutical Sciences
Volume 9, Issue 1
March 2023
Pages 1-14

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