Transsulfuration pathway defects and increased glutathione degradation in severe acute pancreatitis

Sakhawat H. Rahman, Asha R. Srinivasan, Anna Nicolaou

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Glutathione depletion is a consistent feature of the progression of mild to severe acute pancreatitis. In this study, we examined the temporal relationship between cysteine, homocysteine, and cysteinyl-glycine levels; total reduced erythrocyte glutathione; gamma-glutamyl transpeptidase activity; and disease severity. Initially, cysteine concentration was low, at levels similar to those of healthy controls. However, glutathione was reduced whilst cysteinyl glycine and gamma-glutamyl transpeptidase activity were increased in both mild and severe attacks. As the disease progressed, glutathione and cysteinyl glycine were further increased in mild attacks and cysteine levels correlated with homocysteine (r = 0.8, P <0.001) and gamma-glutamyl transpeptidase activity (r = 0.75, P <0.001). The progress of severe attacks was associated with glutathione depletion, reduced gamma-glutamyl transpeptidase activity, and increased cysteinyl glycine that correlated with glutathione depletion (r = 0.99, P = 0.01). These results show that glutathione depletion associated with severe acute pancreatitis occurs despite an adequate cysteine supply and could be attributed to heightened oxidative stress coupled to impaired downstream biosynthesis.
    Original languageEnglish
    Pages (from-to)675-682
    Number of pages7
    JournalDigestive Diseases and Sciences
    Volume54
    Issue number3
    DOIs
    Publication statusPublished - Mar 2009

    Keywords

    • Acute pancreatitis
    • Cysteine
    • Gamma glutamyl transpeptidase
    • Glutathione
    • Homocysteine
    • Oxidative stress

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