Chitosan oligosaccharides reduce acetaminophen-induced hepatotoxicity by suppressing CYP-mediated bioactivation

• Hepatotoxicity was reduced after APAP treatment in rats fed diets containing COS.
• COS reduced CYP-mediated APAP metabolism.
• COS significantly reduced APAP-glutathione and APAP-cysteine contents in liver.
• Rats fed a 3% COS diet had significantly increased Mrp2 expression in liver.

Chitosan oligosaccharides (COS) are functional foods with various biological activities. Acetaminophen (APAP) is a widely used antipyretic and analgesic drug that can cause acute liver injury when taken in overdose. To investigate the effects of COS on the metabolism and toxicity of acetaminophen in rat liver, rats were fed a controlled diet without or with 1% and 3% COS for 5 weeks and were then intraperitoneally injected with acetaminophen. The activity of cytochrome P450 (CYP), phase II enzymes, and membrane transporters in liver were evaluated. Rats fed COS had lower plasma alanine aminotransferase activity and alpha-glutathione-S-transferase protein levels, as indices of hepatotoxicity, after acetaminophen treatment. COS feeding reduced hepatic CYP2E1 and CYP3A activity and acetaminophen–glutathione and acetaminophen–cysteine contents in liver. The 3% COS diet significantly increased multidrug resistance-associated protein 2 expression in the liver. Our results indicate that COS feeding may reduce acetaminophen-induced hepatotoxicity by suppressing CYP-mediated bioactivation.