Pulmonary inflammation, oxidative stress, and fibrosis in a mouse model of cholestasis: the potential protective properties of the dipeptide carnosine

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 396; no. 6; pp. 1129 - 1142
• Main Authors: Ommati, Mohammad Mehdi, Sabouri, Samira, Niknahad, Hossein, Arjmand, Abdollah, Alidaee, Sepideh, Mazloomi, Sahra, Najibi, Asma, Rezaei, Heresh, Ghiasvand, Alireza, Ahmadi, Parinaz, Nikoozadeh, Ahmad, Khodaei, Forouzan, Abdoli, Narges, Azarpira, Negar, Heidari, Reza
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2023; Springer Nature B.V
• Subjects: Alveoli; Animal models; Animals; Anti-inflammatory agents; Bile ducts; Biomarkers; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Carnosine; Carnosine - pharmacology; Carnosine - therapeutic use; Cholestasis; Cholestasis - complications; Cholestasis - drug therapy; Collagen; Dipeptides - pharmacology; Fibrosis; Gallbladder diseases; Humans; Immunoglobulin G; Immunoglobulins; Inflammation; Interleukin 6; Lavage; Ligation - adverse effects; Liver; Lung diseases; Lung Injury - metabolism; Mice; Neurosciences; Oxidative Stress; Pharmacology/Toxicology; Pneumonia - drug therapy; Pneumonia - prevention & control; Rats; Transforming growth factor-b; Tumor necrosis factor-α; Pharmacotherapy; Cirrhosis; Bile acids; Inflammatory cells; Peptide; Pulmonary injury
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-023-02391-y

Cholestasis is a clinical complication that primarily influences the liver. However, it is well known that many other organs could be affected by cholestasis. Lung tissue is a major organ influenced during cholestasis. Cholestasis-induced lung injury could induce severe complications such as respiratory distress, serious pulmonary infections, and tissue fibrosis. Unfortunately, there is no specific pharmacological intervention against this complication. Several studies revealed that oxidative stress and inflammatory response play a role in cholestasis-induced lung injury. Carnosine (CARN) is a dipeptide found at high concentrations in different tissues of humans. CARN’s antioxidant and antiinflammatory properties are repeatedly mentioned in various experimental models. This study aimed to assess the role of CARN on cholestasis-induced lung injury. Rats underwent bile duct ligation (BDL) to induce cholestasis. Broncho-alveolar lavage fluid (BALF) levels of inflammatory cells, pro-inflammatory cytokines, and immunoglobulin were monitored at scheduled intervals (7, 14, and 28 days after BDL). Moreover, lung tissue histopathological alterations and biomarkers of oxidative stress were evaluated. A significant increase in BALF inflammatory cells, TNF-α, IL-1β, IL-6, and immunoglobulin-G (IgG) was detected in the BALF of BDL rats. Moreover, lung tissue histopathological changes, collagen deposition, increased TGF-β, and elevated levels of oxidative stress biomarkers were evident in cholestatic animals. It was found that CARN (100 and 500 mg/kg, i.p.) significantly alleviated lung oxidative stress biomarkers, inflammatory response, tissue fibrosis, and histopathological alterations. These data indicate the potential protective properties of CARN in the management of cholestasis-induced pulmonary damage. The effects of CARN on inflammatory response and oxidative stress biomarkers seems to play a crucial role in its protective properties in the lung of cholestatic animals.