Abstract
Postoperative peritoneal adhesions are considered the major complication following abdominal surgeries. The primary clinical complications of peritoneal adhesion are intestinal obstruction, infertility, pelvic pain, and postoperative mortality. In this study, regarding the anti-inflammatory and antioxidant activities of Crocus sativus, we aimed to evaluate the effects of Crocus sativus on the prevention of postsurgical-induced peritoneal adhesion. Male Wistar-Albino rats were used to investigate the preventive effects of C. sativus extract (0.5%, 0.25% and 0.125% w/v) against postsurgical-induced peritoneal adhesion compared to pirfenidone (PFD, 7.5% w/v). We also investigated the protective effects of PFD (100 μg/ml) and C. sativus extract (100, 200, and 400 μg/ml) in TGF-β1-induced fibrotic macrophage polarization. The levels of cell proliferation and oxidative, antioxidative, inflammatory and anti-inflammatory, fibrosis, and angiogenesis biomarkers were evaluated both in vivo and in vitro models. C. sativus extract ameliorates postoperational-induced peritoneal adhesion development by attenuating oxidative stress [malondialdehyde (MDA)]; inflammatory mediators [interleukin- (IL-) 6, tumour necrosis factor- (TNF-) α, and prostaglandin E2 (PGE2)]; fibrosis [transforming growth factor- (TGF-) β1, IL-4, and plasminogen activator inhibitor (PAI)]; and angiogenesis [vascular endothelial growth factor (VEGF)] markers, while propagating antioxidant [glutathione (GSH)], anti-inflammatory (IL-10), and fibrinolytic [tissue plasminogen activator (tPA)] markers and tPA/PAI ratio. In a cellular model, we revealed that the extract, without any toxicity, regulated the levels of cell proliferation and inflammatory (TNF-α), angiogenesis (VEGF), anti-inflammatory (IL-10), M1 [inducible nitric oxide synthase (iNOS)] and M2 [arginase-1 (Arg 1)] biomarkers, and iNOS/Arg-1 ratio towards antifibrotic M1 phenotype of macrophage, in a concentration-dependent manner. Taken together, the current study indicated that C. sativus reduces peritoneal adhesion formation by modulating the macrophage polarization from M2 towards M1 cells.
Highlights
Postoperative peritoneal adhesions are considered the major complication after abdominal surgery
Our results indicated that the highest concentration of C. sativus extract (400 μg/ml, P < 0:05) and PFD (100 μg/ml, P < 0:001) could increase the inducible nitric oxide synthase (iNOS)/Arg-1 ratio compared to the transforming growth factor- (TGF-)β1 group (Figure 10(c))
The current study demonstrated that C. sativus extract ameliorates postoperational-induced peritoneal adhesion development through attenuating oxidative stress (MDA), inflammatory mediators (IL-6, tumour necrosis factor- (TNF-)α, and prostaglandin E2 (PGE2)), and fibrosis (TGF-β1, IL-4, and plasminogen activator inhibitor (PAI)) and angiogenesis (VEGF) markers, while propagating antioxidant (GSH), anti-inflammatory (IL-10), and fibrinolytic markers and tissue plasminogen activator (tPA)/PAI ratio
Summary
Postoperative peritoneal adhesions are considered the major complication after abdominal surgery. Peritoneal adhesion is an abnormal connective tissue that occurs between two tissues that have been damaged during the surgery [1, 2]. The peritoneum gets harmed and forms a temporary matrix during the surgery. After several hours, this provisional matrix becomes a clot, which can be destroyed by various factors such as macrophages and fibrinolysin enzymes. Following the clot formation after 72 hours, the fibroblasts of the underlying tissues migrate into the clot and provide a field for forming sticky tissue [3, 4]. It has been emphasised that inflammation, free radicals, hypoxia, coagulation, and fibrinolysis are the main pathophysiological reasons responsible for forming peritoneal adhesion [2, 5]
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