Increased oxidative stress and toxicity in ADH and CYP2E1 overexpressing human hepatoma VL-17A cells exposed to high glucose

Karthikeyan Chandrasekaran, Kavitha Swaminathan, S. Mathan Kumar, Dahn L Clemens, Aparajita Dey

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

High glucose mediated oxidative stress and cell death is a well documented phenomenon. Using VL-17A cells which are HepG2 cells over-expressing alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1) and control HepG2 cells, the association of ADH and CYP2E1 with high glucose mediated oxidative stress and toxicity in liver cells was investigated. Cell viability was measured and apoptosis or necrosis was determined through caspase-3 activity, Annexin V-propidium iodide staining and detecting decreases in mitochondrial membrane potential. Reactive oxygen species, lipid peroxidation and the formation of advanced glycated-end products were assessed. The levels of several antioxidants which included glutathione, glutathione peroxidase, catalase and superoxide dismutase were altered in high glucose treated VL-17A cells. Greater toxicity was observed in VL-17A cells exposed to high glucose when compared to HepG2 cells. Oxidative stress parameters were greatly increased in high glucose exposed VL-17A cells and apoptotic cell death was observed. Inhibition of CYP2E1 or caspase 3 or addition of the antioxidant trolox led to significant decreases in high glucose mediated oxidative stress and toxicity. Thus, the over-expression of ADH and CYP2E1 in liver cells is associated with increased high glucose mediated oxidative stress and toxicity.

Original languageEnglish (US)
Pages (from-to)550-563
Number of pages14
JournalIntegrative Biology
Volume4
Issue number5
DOIs
StatePublished - May 1 2012

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Cytochrome P-450 CYP2E1
Oxidative stress
Alcohol Dehydrogenase
Toxicity
Hepatocellular Carcinoma
Oxidative Stress
Glucose
Hep G2 Cells
Cell death
Caspase 3
Liver
Cell Death
Antioxidants
Propidium
Mitochondrial Membrane Potential
Annexin A5
Glutathione Peroxidase
Catalase
Lipid Peroxidation
Superoxide Dismutase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Increased oxidative stress and toxicity in ADH and CYP2E1 overexpressing human hepatoma VL-17A cells exposed to high glucose. / Chandrasekaran, Karthikeyan; Swaminathan, Kavitha; Kumar, S. Mathan; Clemens, Dahn L; Dey, Aparajita.

In: Integrative Biology, Vol. 4, No. 5, 01.05.2012, p. 550-563.

Research output: Contribution to journalReview article

Chandrasekaran, Karthikeyan ; Swaminathan, Kavitha ; Kumar, S. Mathan ; Clemens, Dahn L ; Dey, Aparajita. / Increased oxidative stress and toxicity in ADH and CYP2E1 overexpressing human hepatoma VL-17A cells exposed to high glucose. In: Integrative Biology. 2012 ; Vol. 4, No. 5. pp. 550-563.
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