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

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A Correction to this article was published on 16 March 2023

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Abstract

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.

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Funding

Natural Science Foundation of Shanxi financially supported this project (20210302124411). Grants 23040/23028/23031/23701 from the Vice-Chancellor of Research Affairs, Shiraz University of Medical Sciences, Shiraz, Iran, were also used for this investigation.

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Author notes

  1. Mohammad Mehdi Ommati, Samira Sabouri, and Hossein Niknahad contributed equally.

Authors and Affiliations

  1. College of Veterinary Medicine, Shanxi Agricultural University, Taigu, China

    Mohammad Mehdi Ommati & Samira Sabouri

  2. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Fars, Iran

    Mohammad Mehdi Ommati, Hossein Niknahad, Sepideh Alidaee, Sahra Mazloomi, Asma Najibi, Heresh Rezaei, Parinaz Ahmadi, Ahmad Nikoozadeh & Reza Heidari

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abdollah Arjmand

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

    Sepideh Alidaee, Sahra Mazloomi, Asma Najibi, Heresh Rezaei, Parinaz Ahmadi & Ahmad Nikoozadeh

  5. School of Natural Sciences, University of Tasmania, Hobart, Tasmania, 7001, Australia

    Alireza Ghiasvand

  6. Food and Supplements Safety Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Forouzan Khodaei

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

    Narges Abdoli

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

    Negar Azarpira

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  1. Mohammad Mehdi Ommati
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Contributions

M.M. Ommati, R. Heidari, N. Azarpira, A. Ghiasvand, and H. Niknahad were involved in funding acquisition, subject conceptualization, validation, methodology, data analysis, resources management, project administration, and supervision, writing the original draft, and review and editing the manuscript. S. Sabouri, A. Arjmand, S. Alidaee, S. Mazloomi, A. Najibi, A. Nikoozadeh, P. Ahmadi, H. Rezaei, F. Khodaei, and N. Abdoli were involved in the literature review, data visualization, data analysis, and writing the manuscript draft. S. Alidaee, S. Mazloomi, A. Najibi, A. Nikoozadeh, P. Ahmadi, H. Rezaei, and F. Khodaei were involved in data collection. All authors read and confirmed the final version of this manuscript. The authors announced that all data were generated in-house, and no paper mill was used.

Corresponding author

Correspondence to Reza Heidari.

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Competing interests

The authors declare no competing interests.

Ethics approval

The institutional ethics committee approved all experimental animal procedures at Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC.1399.1353). This study does not include any human participants.

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Not applicable. This study contains no human data.

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Ommati, M.M., Sabouri, S., Niknahad, H. et al. Pulmonary inflammation, oxidative stress, and fibrosis in a mouse model of cholestasis: the potential protective properties of the dipeptide carnosine. Naunyn-Schmiedeberg's Arch Pharmacol 396, 1129–1142 (2023). https://doi.org/10.1007/s00210-023-02391-y

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