Figure 9
From: Serotonin Deficiency Exacerbates Acetaminophen-Induced Liver Toxicity In Mice
Schematic representation of the proposed role of 5-HT in APAP-induced hepatic injury.
After administration into the hepatocytes, APAP is first metabolized by the CYP2E1 and generates the NAPQI, which binds with GSH and also increases ROS and RNS formation to initiate the ER stress which involved in GRP78 and CHOP activation. Increased ROS leads to the JNK phosphorylation to damage the mitochondria, which also promotes the phosphorylation of BCL-2 proteins to induce the apoptosis. Meanwhile, inflammatory factors and HIF-1α can be induced with the oxidative stress. During the hepatic self-repair stage, IL-6/STAT3 pathway can be initiated to promote the cell mitosis and facilitate the liver regeneration. In the present study, we prove that 5-HT can reduce APAP hepatotoxicity by inhibiting APAP metabolism, ROS and RNS formation and promoting the hepatocyte proliferation.
