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Cholestasis-Associated Pulmonary Inflammation, Oxidative Stress, and Tissue Fibrosis: The Protective Role of the Biogenic Amine Agmatine.
- Source :
-
Pharmacology [Pharmacology] 2023; Vol. 108 (4), pp. 379-393. Date of Electronic Publication: 2023 May 30. - Publication Year :
- 2023
-
Abstract
- Introduction: Cholestasis is the stoppage of bile flow, leading to the accumulation of potentially cytotoxic bile components in the liver. These cytotoxic molecules affect many organs. Cholestasis-induced lung injury is a severe complication that could lead to tissue fibrosis and respiratory distress. Substantial evidence indicates the role of oxidative stress and inflammatory response in the pathogenesis of cholestasis-associated pulmonary damage. Agmatine (AGM; 1-amino-4-guanidinobutane) is a biogenic amine endogenously synthesized in the human body. This amine provides potent anti-inflammatory and antioxidant properties.<br />Methods: In the current study, a series (six C57BL/6J male mice/group) of bile duct-ligated (BDL) animals were monitored at scheduled intervals (7, 14, and 28 days after the BDL operation) to ensure inflammatory response in their lung tissue (by analyzing their bronchoalveolar lavage fluid [BALF]). It was found that the level of inflammatory cells, pro-inflammatory cytokines, and IgG in the BALF reached their maximum level on day 28 after the BDL surgery. Therefore, other research groups were selected as follows: 1) Sham-operated (2.5 mL/kg normal saline, i.p., for 28 consecutive days), 2) BDL, 3) BDL + AGM (1 mg/kg/day, i.p., for 28 consecutive days), and 4) BDL + AGM (10 mg/kg/day, i.p., for 28 consecutive days). Then, the BALF was monitored at scheduled time intervals (7, 14, and 28 days post-BDL).<br />Results: It was found that pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), bile acids, bilirubin, and inflammatory cells (monocytes, neutrophils, and lymphocytes) were significantly increased in the BALF of BDL mice. Moreover, biomarkers of oxidative stress were significantly increased in the pulmonary tissue of cholestatic animals. Lung tissue histopathological changes, tissue collagen deposition, and increased TGF-β were also detected. It was found that AGM significantly ameliorated cholestasis-induced lung injury.<br />Conclusion: The effects of AGM on inflammatory indicators, oxidative stress biomarkers, and tissue fibrosis seem to play a pivotal role in its protective properties.<br /> (© 2023 S. Karger AG, Basel.)
- Subjects :
- Male
Mice
Humans
Animals
Mice, Inbred C57BL
Liver
Oxidative Stress
Fibrosis
Biomarkers metabolism
Cytokines metabolism
Biogenic Amines metabolism
Biogenic Amines pharmacology
Agmatine pharmacology
Agmatine therapeutic use
Agmatine metabolism
Lung Injury
Cholestasis complications
Cholestasis drug therapy
Cholestasis metabolism
Pneumonia drug therapy
Pneumonia prevention & control
Pneumonia complications
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0313
- Volume :
- 108
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 37253339
- Full Text :
- https://doi.org/10.1159/000530307