Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

Abstract

The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ-radiation (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed for 30 days of survival analysis. Administration of EPO improved 30-day survival, alleviated TBI-induced myelosuppression and pancytopenia, by augmenting lymphocytes and other white blood cells in the peripheral blood of rats, while bone marrow and spleen cellularity were restored. EPO post-exposure treatment alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated radiation-induced oxidative stress through the upregulation of the cholinergic anti-inflammatory nicotinic acetylcholine receptor (α-7-nAChR) and the pro-survival Janus kinase-2 and signal transducers and activators of transcription JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats. Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present study establishes the implication of α-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling cascade in the radiomitigative potential of EPO against ARS.

Trans-resveratrol alleviates hepatic and renal injury in γ-irradiated rats

“…These findings were supported by the physiological liver and kidney function measurements and histopathological investigation, whereas the changes in the architecture and functions of these tissues that responded to the oxidative damages and inflammation were observed. These data are in agreement with the previous findings shown in several studies by El Bakary et al, 10 Moustafa and Thabet, 26 Galal et al, 27 and Qin et al 6…”

Amelioration of radiation-induced liver damage by p-coumaric acid in mice

“…Before sacrificed, final body mass of the mice was weighed. Immediately after the mice were sacrificed, the liver tissues were collected, weighed and liver mass index was calculated according to the following equation (Galal et al, 2018 ): …”

Withania somnifera (Ashwagandha) root extract counteract acute and chronic impact of γ-radiation on liver and spleen of rats

“…[26][27] Several studies have reported that the detrimental effects evolved after irradiation were connected to the status of oxidative stress and imbalance of oxidation/ reduction (redox) system. [28][29][30] It seemed that, the ROS generated after γ-radiation exposure attacks antioxidant molecules and resulted in consumption of liver and spleen contents of GSH in ROS neutralization process. In addition, the plenty of ROS interact with the lipid molecules that organized in the cellular structures of liver and spleen causes increasing in tissue contents of MDA which leads in turn to loss of cellular and tissues redox tone and finally the development of oxidative stress.…”

“…Thus, the exposure to γ-radiation induced a status of imbalance between proinflammatory (such as NF-κB and IL-6) and antiinflammatory (IL-10 and α-7nAchR) secretion. [29][30] Also, gamma irradiation endorses the secretion of inflammatory cytokine IL-17 that applies in a variety of biological effects by binding to its receptors which broadly expressed on the surface of numerous cells and has imperative roles in encouraging inflammation. 36 On contrary, the administration of Ag according to the present protocol reveals significant ameliorations in the inflammatory responses of rat's groups exposed to γ-irradiation.…”