Acetaminophen (APAP) is a widely used clinical antipyretic analgesic. It is estimated that approximately 2000 people in Europe and the United States experience acute liver failure each year, and nearly 50% of these cases are drug-induced liver injury caused by APAP. For liver injury caused by APAP, the commonly used drug is N-acetyl-L-cysteine, but it has many side effects. Chitosan oligosaccharide (COS) is processed from naturally occurring chitin through chemical desalting and deproteinization, biological enzymatic hydrolysis and other processes. COS has been reported to have good antibacterial, antiviral, antitumor, and antioxidant properties, as well as anti-obesity and cholesterol-lowering effects. The liver injury caused by APAP is mainly caused by oxidative stress caused by ROS, and COS has significant antioxidant and anti-inflammatory effects.
Xiang Junwei and his team from Guangdong Pharmaceutical University evaluated the protective effect and mechanism of COS with different average molecular weights (MW) on APAP-induced liver injury, in order to further understand the application scope of COS. In this study, Xiang et al. constructed APAP-induced liver injury models in vitro and in vivo to study COS at two MWs, namely COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da). The results showed that COST and COSM could significantly reduce the levels of serum ALT, AST and liver MDA, TNF-α, IL-1β and IL-6, and increase the levels and activities of GSH, SOD, GSH-PX and CAT. Mechanistic studies found that COST and COSM could significantly reduce the expression of CYP2E1, Keap1, p-ASK1/ASK1, P-MKK4/MKK4, P-JNK/JNK, Caspase-3 and Bax in liver and increase Nrf2, HO-1, eNOS, Expression of SOD and Bcl-XL. COST and COSM can promote the activation of liver antioxidant pathways by inhibiting APAP metabolism, inhibiting oxidative damage and apoptosis pathways, and finally ameliorating APAP-induced hepatic oxidative damage. The research was published in the journal Food & Function.
From "The protective effect and mechanism of chitosan oligosaccharide on acetaminophen-induced liver injury"