English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

The mechanistic significance of oxidative stress to fibrogenesis in the methionine and choline-deficient (MCD) diet-induced model of steatohepatitis was evaluated by antioxidant intervention, using either vitamin E or L-2-oxothiazolidine-4-carboxylate (OTC), a cysteine precursor that promotes glutathione synthesis. Significant depletion of hepatic reduced glutathione (GSH) and elevation of thiobarbituric acid reactive substances (TBARS) occurred from week 3 in association with hepatic injury in mice fed the MCD diet. Hepatic stellate cell (HSC) activation and increased collagen alpha1(I) mRNA expression, together with morphologic fibrosis were evident from week 5. Vitamin E repleted GSH, reduced TBARS, steatosis, inflammation, HSC activation and collagen alpha1(I) mRNA expression, and ameliorated fibrosis. Vitamin E did not effect the expression of either profibrogenic cytokines (transforming growth factor-beta 1, connective tissue growth factor) or matrix remodeling enzymes (tissue inhibitor of metalloproteinase-1 and -2, matrix metalloproteinase-2 and -13). Despite repletion of hepatic GSH in OTC-supplemented mice, the initial benefit in the reduction of hepatic TBARS and inhibition of collagen alpha1(I) mRNA expression at week 5, failed to protect these mice from hepatic injury or fibrosis at later time points. Oxidative stress or products of lipid peroxidation mediate HSC activation and collagen gene expression directly in the MCD model of steatohepatitis. Vitamin E but not glutathione augmentation can interrupt this pathogenic process.

Pro-oxidant-mediated hepatic fibrosis and effects of antioxidant intervention in murine dietary steatohepatitis