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Evaluation of the effects of empagliflozin on acute lung injury in rat intestinal ischemia–reperfusion model

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Abstract

Background

Empagliflozin is a selective sodium–glucose co-transporter (SGLT2) inhibitor that is approved for the treatment of type 2 diabetes. The beneficial effects of empagliflozin on other organ systems including the heart and kidneys have been proven. The aim of this study is to evaluate the role of empagliflozin on acute lung injury induced by intestinal ischemia–reperfusion (I/R).

Materials and methods

A total of 27 male Wistar albino rats were divided into three groups: sham, I/R, and I/R + empagliflozin; each group containing nine animals. Sham group rats underwent laparotomy without I/R injury. Rats in the I/R group underwent laparotomy, 1 h of after ischemia–reperfusion injury (superior mesenteric artery ligation was followed by 2 h of reperfusion). Rats in I/R were given empagliflozin (30 mg/kg) by gastric gavage for 7 days before the ischemia–reperfusion injury. All animals were killed at the end of reperfusion and lung tissue samples were obtained for immunohistochemical staining and histopathological investigation in all groups.

Results

Serum glucose, AST, ALT, creatinine, native thiol, total thiol, and disulfide levels and disulfide–native thiol, disulfide–total thiol, and native thiol–total thiol ratios as well as the IMA levels were analyzed and compared among the groups. While intestinal I/R significantly increases serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine levels; did not cause any change in homeostasis parameters and IMA level. Empagliflozin treatment had no significant effect on biochemical parameters. Empagliflozin treatment induced a significant decrease in positive immunostaining for IL-1, IL-6, TNF-alpha, caspase 3, caspase 8, and caspase 9 compared to the I/R group in lung tissue samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces. Empagliflozin treatment significantly attenuated the severity of intestinal I/R injury.

Conclusions

It was concluded that empagliflozin treatment may have beneficial effects in acute lung injury, and, therefore, has the potential for clinical use.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Endocrinology, Ankara Training and Research Hospital, Hacettepe Neighborhood Ulucanlar Caddesi No: 89 Altindag, 06230, Ankara, Turkey

    P. Gokbulut, S. M. Kuskonmaz, G. Koc & C. Culha

  2. Ömer Halisdemir University Training and Research Hospital, Nigde, Turkey

    C. E. Onder

  3. Faculty of Veterinary Medicine, Harran University, Sanlıurfa, Turkey

    N. Yumusak

  4. Department of Biochemistry, Ankara City Hospital, Ankara, Turkey

    O. Erel & A. S. Nural

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  1. P. Gokbulut
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Contributions

PG: substantial contributions to the conception, acquisition, analysis, or interpretation of data for the work drafting of the work, or revising it critically for important intellectual content, final approval of the version to be published, agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SMK: substantial contributions to the conception, drafting the work, final approval of the version to be published, agreement to be accountable for all aspects of the work. GK: design of the work, revising for important intellectual content, final approval of the version to be published, agreement to be accountable for all aspects of the work. CEO: analysis of data for the work,, drafting the work, final approval of the version to be published, agreement to be accountable for all aspects of the work. NY: revising for important intellectual content, final approval of the version to be published, agreement to be accountable for all aspects of the work. OE: substantial contributions to the conception, final approval of the version to be published, agreement to be accountable for all aspects of the work. ASN: substantial contributions to the conception, final approval of the version to be published, agreement to be accountable for all aspects of the work. CC: interpretation of data for the work,, revising for important intellectual content, final approval of the version to be published, agreement to be accountable for all aspects of the work. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

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Correspondence to P. Gokbulut.

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Conflict of interest

The authors declare there are no conflicts of interest.

Ethical approval

The study was conducted according to the ethical standards specified in the 1964 Declaration of Helsinki. Research and publication ethical rules were followed in our study. Our study was approved by the ethics committee of Ankara Training and Research Hospital Animal Experiments Local Ethics Committee, dated 26.07.2021, with a 0066 meeting and 668 decision number.

Informed constent

In our animal study titled ‘Evaluation of the effects of empagliflozin on acute lung injury in rat intestinal ischemia– reperfusion model’, no informed consent is required.

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Gokbulut, P., Kuskonmaz, S.M., Koc, G. et al. Evaluation of the effects of empagliflozin on acute lung injury in rat intestinal ischemia–reperfusion model. J Endocrinol Invest 46, 1017–1026 (2023). https://doi.org/10.1007/s40618-022-01978-1

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