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HPLC Measurement of the DNA Oxidation Biomarker, 8-oxo-7,8-dihydro-2’-deoxyguanosine, in Cultured Cells and Animal Tissues
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Effects of two- and twelve-weeks sodium-glucose cotransporter 2 inhibition on DNA and RNA oxidation: two randomized,

Emil List Larsen1,2, Andreas Andersen3,4, Laura K Kjær1

  • 1Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.

Free Radical Research
|May 12, 2023
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin may reduce oxidative stress in type 2 diabetes. Twelve weeks of dapagliflozin treatment significantly decreased DNA oxidation, while empagliflozin showed no significant effect after two weeks.

Area of Science:

  • Endocrinology and Metabolism
  • Cardiovascular Research
  • Oxidative Stress and Molecular Biology

Background:

  • SGLT2 inhibitors are associated with cardiovascular protective effects in animal models.
  • Oxidative stress, indicated by DNA and RNA oxidation, is implicated in cardiovascular disease.
  • Understanding the impact of SGLT2 inhibition on oxidative stress markers is crucial for clinical applications.

Purpose of the Study:

  • To investigate the effects of short-term (2 weeks) and longer-term (12 weeks) SGLT2 inhibition on DNA and RNA oxidation in individuals with type 2 diabetes.
  • To assess the impact of empagliflozin and dapagliflozin on urinary biomarkers of oxidative damage.

Main Methods:

  • Two randomized trials were conducted in individuals with type 2 diabetes.
  • Trial 1: 31 participants received empagliflozin (25 mg/day) or placebo for 2 weeks.
  • Trial 2: 35 participants received dapagliflozin (10 mg/day) or placebo for 12 weeks in a crossover design.
  • Primary outcome: changes in urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) as markers of DNA and RNA oxidation.

Main Results:

  • Two weeks of empagliflozin treatment did not significantly alter urinary 8-oxodG or 8-oxoGuo levels compared to placebo.
  • Twelve weeks of dapagliflozin treatment resulted in a significant reduction in urinary 8-oxodG/creatinine levels (p=0.01) compared to placebo.
  • Neither empagliflozin nor dapagliflozin significantly affected urinary 8-oxoGuo levels.
  • Plasma ferritin levels correlated with DNA and RNA oxidation.

Conclusions:

  • Short-term empagliflozin treatment (2 weeks) does not impact DNA or RNA oxidation in type 2 diabetes.
  • Longer-term dapagliflozin treatment (12 weeks) demonstrates a significant decrease in DNA oxidation.
  • SGLT2 inhibition may offer protective effects against oxidative stress, particularly with longer treatment durations.
Keywords:
8-oxoGuo8-oxodGdapagliflozinempagliflozinoxidative stress

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