L-ascorbate prevents non-alcoholic steatohepatitis-based hepatocarcinogenesis in Sod1/Prdx4 double-knockout mice.

ABSTRACT: Superoxide dismutase 1 (Sod1) and peroxiredoxin 4 (Prdx4) double knockout (DKO) causes symptoms similar to non-alcoholic steatohepatitis (NASH) even at younger ages. This study revealed that DKO mice exhibited high mortality, and surviving DKO mice developed hepatocellular carcinoma within the first year of life. Administration of physiological doses of L-ascorbate (Asc; 1.5 mg/mL) in drinking water reduced mortality and effectively prevented tumor development. Oxidative stress due to SOD1 deficiency and endoplasmic reticulum stress due to PRDX4 deficiency may promote NASH, ultimately leading to hepatocarcinogenesis. Analyses of liver tissues from 8-month-old DKO mice revealed that Asc supplementation robustly suppressed upregulation of amino acid metabolic pathways observed in DKO mice. T

SUBMITTER: Osaki T 

PROVIDER: S-EPMC12722311 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature