Journal
AGING-US
Volume 13, Issue 6, Pages 7800-7827Publisher
IMPACT JOURNALS LLC
Keywords
APAP; aging; inflammation; liver; oxidative stress
Categories
Funding
- AEI/FEDER, UE [SAF2016-75004-R, PID2019-108977RB-100, RTI2018-094052-B-100]
- Fundacion Ramon Areces (Spain)
- CIBERdem (ISCIII)
- ISCIII/FEDER, UE [PI17/00535]
- [S2017/BMD-3686]
- [S2017/BMD-3684]
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The chronic infratherapeutic APAP treatment protects mice from age-related liver alterations by attenuating oxidative stress and inflammation.
The 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.
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