The Role of Alpha-1 and Alpha-2 Adrenoceptors in Restraint Stress-Induced Liver Injury in Mice

Abstract

Acute stress affects cellular integrity in many tissues including the liver, but its underlying mechanism is still unclear. The aim of the present study was to investigate the potential involvement of catecholamines and adrenoceptors in the regulation of acute restraint stress-induced liver injury. Restraint was achieved by placing mice in restraint tubes. Mice were treated with either an α-l antagonist, prazosin, an α-2 antagonist, yohimbine, a β-l antagonist, betaxolol, a β-2 antagonist, ICI 118551, or a central and peripheral catecholamine depleting agent, reserpine, and followed by restraint stress. Assessment of liver injury (serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) , hepatic total GSH, GSSG and GSH/GSSG ratio) , histopathology and of apoptosis, by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay and western blotting, was performed. Three hours of restraint stress resulted in liver injury, as indexed by elevated serum transaminase levels, decreased hepatic total GSH levels and GSH/GSSG ratio, increased hepatic GSSG levels as well as enhanced hepatocytes apoptosis. Either reserpine or prazosin or yohimbine was found to attenuate liver injury. Furthermore, prazosin and yohimbine protected against restraint-induced hepatocytes apoptosis through attenuating the activation of caspases-9 and -3 and reducing the Bax/Bcl-2 ratio. These results suggest that α-1 and α-2 adrenoceptors mediate restraint-induced liver oxidative injury through caspase-9 and Bcl-2 family of apoptotic regulatory proteins.

Preventive effect of omega‐3 fatty acids in a rat model of stress‐induced liver injury

“…In this study, exposure of rats to acute CRS has resulted in hepatic damage and inflammation that was confirmed by histological examination. Zhu et al () reported that exacerbation in oxidative stress can be the result of not only an increase in ROS but also due to decrease in antioxidant capacity, which is in agreement with results of this study, as acute CRS has resulted in significant increase in hepatic MDA and decrease in TAC levels that is also as found by Dekanski et al ().…”

“…Our results showed that the expression of caspase‐3 was significantly increased in acute CRS group as compared with either control or omega‐3 group that is as found by Zhu et al () and Fayez, Awad, El‐Naa, Kenawy, and El‐Sayed (). Zhang, Li, Han, and Shi () stated that the induced activation of caspases results in upregulation of caspase‐9 and caspase‐3 and leads to dysfunction of mitochondria that in turn promotes the apoptotic process.…”

Near-infrared photobiomodulation combined with coenzyme Q10 for depression in a mouse model of restraint stress: reduction in oxidative stress, neuroinflammation, and apoptosis

“…In response to stress condition, pro-apoptotic (BAX) and anti-apoptotic (Bcl-2) proteins regulate the release of cytochrome c from the outer mitochondrial membrane, which activates caspases and thus triggers apoptosis (Kubera, et al, 2011). It has been shown that restraint stress causes cellular apoptosis through activation of caspases-9 and −3 and increase in the BAX/Bcl-2 ratio (Zhu et al, 2014). In our study, sub-chronic restraint stress for 5 days produced a pro-apoptotic response, as evidenced by increased BAX/Bcl-2 ratio and elevated caspase-9 and caspase-3 activities in the PFC and HIP.…”

Restoration of Memory and Acetylcholinesterase Activity by Michelia Champaca in Chronically Noise Stressed Wistar Albino Rats

“…Stress is an integral component of human life and is considered as any condition that leads to perturbation of the body's homeostasis [11]. During extreme stress situations, the homeostatic mechanisms of the organism become deficient and the survival of the organism is thereby threatened.…”