Abstract
CD5 molecule like (CD5L), a member of the scavenger receptor cysteine-rich domain superfamily, plays a critical role in immune homeostasis and inflammatory disease. Acetaminophen (APAP) is a safe and effective antipyretic analgesic. However, overdose may cause liver damage or even liver failure. APAP hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response, in which the role of CD5L remains to be investigated. In this study, we found that the expression of CD5L was increased in the livers of mice after APAP overdose. Furthermore, CD5L deficiency reduced the increase of alanine transaminase (ALT) level, histopathologic lesion area, c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK) phosphorylation level, Transferase-Mediated dUTP Nick End-Labeling positive (TUNEL+) cells proportion, vascular endothelial cell permeability and release of inflammatory cytokines induced by excess APAP. Therefore, our findings reveal that CD5L may be a potential therapeutic target for prevention and treatment of APAP-induced liver injury.
Highlights
Acetaminophen (APAP), one of the most widely used analgesicantipyretic in the United States, is safe at therapeutic doses
CD5 molecule like (CD5L) deficiency attenuates APAP-induced liver injury in mice To determine the role of CD5L in APAP-induced liver injury, male WT mice fasted overnight were treated with 300 mg/kg of APAP by intraperitoneal injection
Under physiological conditions, CD5L was only expressed in the interstitium of liver tissue, while APAP overdose induced its expression in liver parenchymal cells in the necrotic area around the central vein besides the mesenchymal
Summary
Acetaminophen (APAP), one of the most widely used analgesicantipyretic in the United States, is safe at therapeutic doses. Various studies suggest that oxidative stress and proinflammatory factors such as interleukin-6 (IL-6) activate the JNK signaling pathway [4] and associated with ERK signaling pathway [5, 6]. CD5L is found to be associated with various diseases such as lipid metabolic disease [12], hepatocellular carcinoma [13, 14], fungus induced peritonitis [15], acute kidney injury [16] and myocardial infarction [17] in later studies. Results showed that the expression of CD5L was induced in the development of APAP-induced liver injury. CD5L-deficient reduced APAP-induced liver injury in mice by impairing the activation of JNK and ERK signaling pathways
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