Chronic treatment with acetaminophen protects against liver aging by targeting inflammation and oxidative stress

28 páginas, 7 figuras, 2 tablasThe liver exhibits a variety of functions that are well-preserved during aging. However, the cellular hallmarks of aging increase the risk of hepatic alterations and development of chronic liver diseases. Acetaminophen (APAP) is a first choice for relieving mild-to-moderate pain. Most of the knowledge about APAP-mediated hepatotoxicity arises from acute overdose studies due to massive oxidative stress and inflammation, but little is known about its effect in age-related liver inflammation after chronic exposure. Our results show that chronic treatment of wild-type mice on the B6D2JRcc/Hsd genetic background with APAP at an infratherapeutic dose reduces liver alterations during aging without affecting body weight. This intervention attenuates age-induced mild oxidative stress by increasing HO-1, MnSOD and NQO1 protein levels and reducing ERK1/2 and p38 MAPK phosphorylation. More importantly, APAP treatment counteracts the increase in Cd8+ and the reduction in Cd4+ T lymphocytes observed in the liver with age. This response was also found in peripheral blood mononuclear cells. In conclusion, chronic infratherapeutic APAP treatment protects mice from age-related liver alterations by attenuating oxidative stress and inflammation.SAF2016-75004-R, PID2019-108977RB-100 (AEI/FEDER, UE) to P. M-S. and M.C. and S2017/BMD-3686 (CM) to P. M-S, RTI2018-094052-B-100 (AEI/FEDER, UE), S2017/BMD-3684 (CM), Fundación Ramón Areces (Spain) and CIBERdem (ISCIII) to A.M.V., and PI17/00535 (ISCIII/FEDER, UE) to C. G-M.Peer reviewe