title: Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum.
abstract: It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 μg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1β and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1β and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1β and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.
authors.affiliation: Dr Lutfi Kirdar Kartal Training and Research Hospital, Radiation Oncology, 34865 Istanbul, Turkey.
authors.forename: Hazan
authors.initials: H
authors.lastname: Özyurt
authors.affiliation: Dr Lutfi Kirdar Kartal Training and Research Hospital, Radiation Oncology, 34865 Istanbul, Turkey.
authors.forename: A Sevgi
authors.initials: AS
authors.lastname: Özden
authors.affiliation: Cumhuriyet University School of Pharmacy, Department of Biochemistry, 58140 Sivas, Turkey.
authors.forename: Özge
authors.initials: Ö
authors.lastname: Çevik
authors.affiliation: Marmara University Pendik Training and Research Hospital, Radiation Oncology, Üst Kaynarca, Istanbul, Turkey.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: Özgen
authors.affiliation: Marmara University School of Pharmacy, Pharmacology, 34668 Istanbul, Turkey.
authors.forename: Selin
authors.initials: S
authors.lastname: Cadirci
authors.affiliation: Marmara University School of Medicine, Department of Histology and Embryology, Başıbüyük Health Campus, Basic Medical Sciences Building, Başıbüyük, Maltepe, 34854 Istanbul, Turkey.
authors.forename: Merve Açıkel
authors.initials: MA
authors.lastname: Elmas
authors.affiliation: Marmara University School of Medicine, Department of Histology and Embryology, Başıbüyük Health Campus, Basic Medical Sciences Building, Başıbüyük, Maltepe, 34854 Istanbul, Turkey.
authors.forename: Feriha
authors.initials: F
authors.lastname: Ercan
authors.affiliation: Marmara University School of Pharmacy, Pharmacology, 34668 Istanbul, Turkey.
authors.forename: Göksel
authors.initials: G
authors.lastname: Şener
authors.affiliation: Marmara University School of Medicine, Department of Medical Pharmacology, Başıbüyük Health Campus, Basic Medical Sciences Building, Başıbüyük, Maltepe, 34854 Istanbul, Turkey zgoren@gmail.com.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Gören
mesh_terms: D000109:Acetylcholine / Q000276:immunology*; D000818:Animals; D018678:Cholinergic Agents / Q000008:administration & dosage; D016207:Cytokines / Q000276:immunology; D007077:Ileal Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018678:Cholinergic Agents; D016207:Cytokines; D000109:Acetylcholine
keywords: IL-10; IL-1β; TNF-α; caspase-3; myeloperoxidase activity