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.

Changes in splenic uptake pattern associated with X-ray irradiation

“…The 8 Gy dose used in this work was based on previous studies conducted in rats [ 27 , 28 , 29 ]. Other doses of radiation and even fractionated schemes may be probably adequate and applicable in the treatment of specific tumors.…”

Radiation-induced liver disease: current understanding and future perspectives

“…When SD rats were exposed to an 8 Gy single dose of abdominal irradiation, severe sinusoidal congestion and hemorrhage, dilation of the central vein, degenerated HCs with perinuclear vacuolization and activated KCs were observed in the irradiated livers 36 h after exposure. 48 However, when the Wistar rats were exposed to a 25 Gy single dose of hepatic irradiation, only mild hepatocellular damage and steatosis were observed 24 and 48 h after irradiation. 49 These findings indicate that Wistar rats may be more radioresistant than SD rats, presenting strain disparity in responses to radiation.…”

Radiation-Induced Reactions in the Liver—Modulation of Radiation Effects by Lifestyle-Related Factors—

“…Other studies have examined alterations to protein expression [35,36]. In particular, proteins related to inflammation or apoptosis seem to contribute to the effects of irradiation on the liver [36,37]. High-dose radiation usually induces inflammation, leading to fibrosis or cancer.…”