Regulatory role of growth factors during N-acetylcysteine administration in the model of radiation-induced pancreatic injury

Purpose of the study. To evaluate the roles of the growth factors IGF‑1, TGF-β, and VEGF-A in regulating delayed regenerative mechanisms induced by N-acetylcysteine (NAC) administered prior to local pancreatic irradiation with electrons at a total dose of 30 Gy.

Materials and methods. An experimental study was conducted on 60 male Wistar rats, which were divided into four groups: Group 1 (control, n = 10): rats received an intraperitoneal injection of NaCl solution without local electron irradiation; Group 2 (n = 20): intraperitoneal administration of 0.9 % NaCl solution prior to local electron irradiation in a fractionated mode with a total focal dose (TFD) of 30 Gy; Group 3 (n = 20): intraperitoneal administration of N-AC at a dose of 120 mg/kg prior to local electron irradiation in a fractionated mode with a TFD of 30 Gy; Group 4 (n = 10): intraperitoneal administration of N-AC at a dose of 120 mg/kg without local electron irradiation. Thirty days after irradiation, blood levels of glucose, insulin, and amylase were measured. Histological analysis of pancreatic islet architecture, the degree of perivascular fibrosis (Masson’s trichrome staining), and the expression of IGF‑1, TGF-β, and VEGF-A were assessed by immunohistochemistry through counting positively stained cells.

Results. Irradiation resulted in elevated blood glucose and amylase levels and decreased insulin levels. Signs of radiation-induced pancreatic injury were accompanied by reduced expression of IGF‑1 and VEGF-A in the islets by 39 % and 56 %, respectively, while the proportion of TGF-β-positive cells exceeded the control values by 3.4‑fold. Pre-irradiation administration of NAC partially preserved biochemical parameters within the normal range, suppressed TGF-β expression, and maintained the numbers of IGF‑1- and VEGF-A-positive endocrine cells at levels 2.5 and 3 times higher than those in the irradiation-only group, respectively.

Conclusion. Pre-irradiation administration of NAC exerts a modulatory effect on the expression of growth factors IGF‑1, TGF-β, and VEGF-A in the late period following local electron irradiation of the pancreas, promoting restoration of the organ’s structural integrity and endocrine function. The obtained data suggest that N-AC is a promising agent for the prevention of delayed post-radiation complications, including fibrosis as well as metabolic and secretory insufficiency of the pancreatic islets.

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