title: Modulation of GSH with exogenous agents leads to changes in glyoxalase 1 enzyme activity in VL-17A cells exposed to chronic alcohol plus high glucose.
abstract: Gluthathione (GSH) is a major cellular antioxidant. The present study utilizing VL-17A cells exposed to chronic alcohol plus high glucose investigated the changes in oxidative stress, toxicity, and glyoxalase 1 activity as a detoxification pathway due to changes in GSH level through GSH supplementation with N-acetyl cysteine (NAC) or ursodeoxycholic acid (UDCA) and its depletion through buthionine sulfoximine (BSO) or diethyl maleate (DEM). Glyoxalase 1 plays an important role in detoxification of methylglyoxal which is formed as a precursor of advanced glycated end products formed due to high glucose mediated oxidative stress. Significant changes in glyoxalase 1 activity utilizing methylglyoxal or glyoxal as substrates occurred with NAC or UDCA or BSO or DEM supplementation in chronic alcohol plus high glucose treated VL-17A cells. NAC or UDCA administration in chronic alcohol plus high glucose treated VL-17A cells increased viability and decreased ROS levels, lipid peroxidation and 3-nitrotyrosine adduct formation. Similarly, GSH depletion with BSO or DEM had an opposite effect on the parameters in chronic alcohol plus high glucose treated VL-17A cells. In conclusion, modulation of GSH with NAC or UDCA or BSO or DEM leads to significant changes in oxidative stress, glyoxalase 1 enzyme activity and toxicity in chronic alcohol plus high glucose treated VL-17A cells.
authors.affiliation: Life Science Division, AU-KBC Research Centre, MIT Campus of Anna University, Chromepet, Chennai-600044, India. aparajitabhu@rediffmail.com aparajitadey21@gmail.com aparajita@au-kbc.org.
authors.forename: S Mathan
authors.initials: SM
authors.lastname: Kumar
authors.forename: Kavitha
authors.initials: K
authors.lastname: Swaminathan
authors.forename: Dahn L
authors.initials: DL
authors.lastname: Clemens
authors.forename: Aparajita
authors.initials: A
authors.lastname: Dey
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002477:Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005947:Glucose / Q000009:adverse effects / Q000032:analysis; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000431:Ethanol; D007791:Lactoylglutathione Lyase; D005978:Glutathione; D005947:Glucose