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

Inflammopharmacology. 2024 Apr;32(2):1077-1089. doi: 10.1007/s10787-023-01417-4. Epub 2024 Feb 3.

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.

Keywords: d-limonene; Adhesion prevention; Inflammation; Oxidative stress; Postoperative peritoneal adhesions; Rats.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants* / pharmacology
  • Limonene / pharmacology
  • Rats
  • Transforming Growth Factor beta1*
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A

Substances

  • Transforming Growth Factor beta1
  • Limonene
  • Antioxidants
  • Vascular Endothelial Growth Factor A
  • Tumor Necrosis Factor-alpha
  • Anti-Inflammatory Agents