biostudies-literatureMohammed SBLRD VANIA NIH HHSOklahoma Center for the Advancement of Science and TechnologyPresbyterian Health FoundationU.S. Department of Veterans AffairsNational Institute on Aging315-328https://www.ebi.ac.uk/biostudies/studies/S-EPMC8845573biostudies-literatureUnknown164Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1^-/- or Sod1KO mice) have increased oxidative stress, show accelerated aging and develop spontaneous hepatocellular carcinoma (HCC) with age. Similar to humans, HCC development in Sod1KO mice progresses from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Oxidative stress plays a role in NAFLD to NASH progression, and liver inflammation is the main mechanism that drives the disease progression from NASH to fibrosis. Because necroptosis is a major source of inflammation, we tested the hypothesis that increased necroptosis in the liver plays a role in increased inflammation and fibrosis in Sod1KO mice. Phosphorylation of MLKL Free radical biology & medicineRole of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress.PMC8845573P30 AG050911R01 AG059718IK6 BX005238R01 AG057424I01 BX004538Nicklas EHRichardson AThadathil NKinter MMohammed SSelvarani RRoyce GHDeepa SSfalseRole of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress.Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1^-/- or Sod1KO mice) have increased oxidative stress, show accelerated aging and develop spontaneous hepatocellular carcinoma (HCC) with age. Similar to humans, HCC development in Sod1KO mice progresses from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Oxidative stress plays a role in NAFLD to NASH progression, and liver inflammation is the main mechanism that drives the disease progression from NASH to fibrosis. Because necroptosis is a major source of inflammation, we tested the hypothesis that increased necroptosis in the liver plays a role in increased inflammation and fibrosis in Sod1KO mice. Phosphorylation of MLKL 2021-01-01T00:00:00Z2021 Feb2025-04-04T14:58:47.538Z2025-04-04T14:58:47.538ZS-EPMC88455733342902210.1016/j.freeradbiomed.2020.12.449