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D-limonene inhibits peritoneal adhesion formation in rats via anti-inflammatory, anti-angiogenic, and antioxidative effects

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Abstract

The aim of this research was to investigate the effects of d-limonene on decreasing post-operative adhesion in rats and to understand the mechanisms involved. Peritoneal adhesions were induced by creating different incisions and excising a 1 × 1 cm section of the peritoneum. The experimental groups included a sham group, a control group in which peritoneal adhesions were induced without any treatment, and two treatment groups in which animals received d-limonene with dosages of 25 and 50 mg/kg after inducing peritoneal adhesions. Macroscopic examination of adhesions showed that both treatment groups had reduced adhesion bands in comparison to the control group. Immunohistochemical assessment of TGF-β1, TNF-α, and VEGF on day 14 revealed a significant increment in the level of immunopositive cells for the mentioned markers in the control group, whereas administration of limonene in both doses significantly reduced levels of TGF-β1, TNF-α, and VEGF (P < 0.05). Induction of peritoneal adhesions in the control group significantly increased TGF-β1, TNF-α, and VEGF on days 3 and 14 in western blot evaluation, while treatment with limonene significantly reduced TNF-α level on day 14 (P < 0.05). Moreover, VEGF levels in both treatment groups significantly reduced on days 3 and 14. In the control group, a significant increment in the levels of MDA and NO and a notable decline in the levels of GPX, CAT was observed (P < 0.05). Limonene 50 group significantly reduced MDA level and increased GPx and CAT levels on day 14 (P < 0.05). In summary, d-limonene reduced adhesion bands, inflammatory cytokines, angiogenesis, and oxidative stress.

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Data availability

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

Abbreviations

ROS:

Reactive oxygen species

MDA:

Malondialdehyde

GPx:

Glutathione peroxidase

CAT:

Catalase

NO:

Nitric oxide

IHC:

Immunohistochemistry

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Acknowledgements

This study was extracted from the Doctor of Veterinary Medicine (DVM) thesis of Ali Razazi.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Veterinary, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran

    Ali Razazi & Behnam Pedram

  2. Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran

    Ali Kakanezhadi & Abbas Raisi

  3. Department of Pathobiology, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran

    Omid Dezfoulian

  4. Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

    Farshid Davoodi

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Contributions

AR & AK:Conceptualization, Methodology, Investigation, Writing—Original Draft. AR: Project administration, Investigation, Writing—Original Draft, Writing—Review & Editing. BP: Conceptualization, Methodology. OD: Writing—Original Draft, Methodology, Writing—Review & Editing. FD: Visualization, Resources, Writing—Review & Editing, Formal analysis.

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Correspondence to Abbas Raisi or Omid Dezfoulian.

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During the preparation of this work, the author(s) used chatGPT to paraphrase some sections of the manuscript. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication. The authors have no relevant financial or non-financial interests to disclose.

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Razazi, A., Kakanezhadi, A., Raisi, A. et al. D-limonene inhibits peritoneal adhesion formation in rats via anti-inflammatory, anti-angiogenic, and antioxidative effects. Inflammopharmacol 32, 1077–1089 (2024). https://doi.org/10.1007/s10787-023-01417-4

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