Isotretinoin therapy induces DNA oxidative damage

Clin Chem Lab Med. 2005;43(11):1178-82. doi: 10.1515/CCLM.2005.204.

Abstract

Background: Isotretinoin (Iso) is currently indicated for the treatment of cystic acne (CA) and is related to marked teratogenicity.

Aim: The aim of the study was to evaluate the relationship between total antioxidant status (TAS) and a serum marker of DNA oxidative damage, 8-hydroxy-2-desoxyguanosine (8-OHdG), in patients on Iso treatment.

Patients and methods: Patients with CA (n=18) were evaluated before and 45 days after Iso (0.5 mg/kg per day) treatment and non-diseased controls (n=22) were tested only once. Plasma TAS levels and 8-OHdG were measured spectrophotometrically and with an immunoassay, respectively. Liver biochemical parameters and muscle enzymes were measured on a blood chemistry analyzer.

Results: TAS levels were significantly (p<0.0001) lower in patients before treatment (921+/-124 micromol/L) compared with those after treatment (1335+/-93 micromol/L) and in controls (1536+/-126 micromol/L). In contrast, 8-OHdG serum levels were two-fold higher in patients after treatment (0.21+/-0.03 ng/mL) than before treatment (0.11+/-0.02 ng/mL) and three-fold higher than in controls (0.07+/-0.01 ng/mL; p<0.0001). Negative correlations were found between TAS and 8-OHdG (r=-0.754, p<0.0001) in patients before therapy and positive correlations were found between creatine kinase (CK) and 8-OHdG (r=0.488, p<0.001) and liver enzymes after Iso treatment.

Conclusions: High serum levels of 8-OHdG in patients on Iso therapy may be due to a direct effect of Iso on liver, muscle and skin epidermal cells. Regular evaluation of 8-OHdG in sera of patients, especially of women of reproductive age, on Iso treatment could be a sensitive follow-up biomarker of DNA oxidation.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adolescent
  • Adult
  • Antioxidants / metabolism
  • DNA Damage / drug effects*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Dermatologic Agents / adverse effects*
  • Female
  • Humans
  • Isotretinoin / adverse effects*
  • Liver / enzymology
  • Male
  • Muscle, Skeletal / enzymology
  • Muscular Diseases / chemically induced
  • Oxidative Stress / drug effects*

Substances

  • Antioxidants
  • Dermatologic Agents
  • 8-Hydroxy-2'-Deoxyguanosine
  • Isotretinoin
  • Deoxyguanosine