Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

Abstract

The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.

LASP-1 promotes tumor proliferation and metastasis and is an independent unfavorable prognostic factor in gastric cancer

“…Western blot analysis was performed according to a standard method as described previously (Yu et al 2013). A polyclonal LASP-1 antibody (1:2,000; Millipore, Billerica, MA, USA) was used.…”

Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model

“…We also found that cell death actually decreased following treatment with NAS, suggesting increased gut epithelial cell turnover. The anti-apoptotic effects of NAS have been demonstrated in several experiments 16,34 and were attributed to the influence on mitochondrial permeability transition pore opening, mitochondrial fragmentation, inhibition of the subsequent release of apoptogenic factors cytochrome c, Smac, and apoptosis-inducing factor from mitochondria to cytoplasm, along with activation of caspase-3 and -9. Treatment of IR rats with NAS was accompanied by a downregulation of TLR-4 signaling related adaptor-associated proteins.…”

“…14 Both melatonin and its precursor, N-acetylserotonin (NAS), have been shown to possess antioxidant activities, both in vivo and in vitro; however, following some claims, NAS is a more effective extra-and intracellular antioxidant than melatonin. 15 The positive effects of NAS in the prevention of IR-induced tissue damage have been observed in the liver 16 and heart. 17 In this study, we examined the effect of NAS administration on TLR-4, MyD88, and TRAF6 mRNA expression in the small intestine following intestinal IR in a rat model.…”

Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia–Reperfusion Injury in a Rat

“…4 IR injury is mediated by a complex chain of events involving adenosine triphosphate depletion, membrane integrity disruption, ionic homeostasis alteration, ROS production, and apoptosis. 7,10,11 Experimental studies suggest that ROS generated during reperfusion of tissue have an important role in the basic pathophysiology of IR injury. ROS have the ability to damage DNA, proteins, and lipids.…”

“…The NAS may also protect against oxidative stress-related disorders, such as cell death, mutagenesis, aging, and diseases such as sepsis, cancer, postischemic trauma, Alzheimer disease, and Parkinson disease. 7 However, there are no data on the effect of NAS on intestinal recovery following gut IR injury in animal models.…”