Isotretinoin therapy induces DNA oxidative damage

Abstract

AbstractBackground: 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 45days after Iso (0.5mg/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±124μmol/L) compared with those after treatment (1335±93μmol/L) and in controls (1536±126μmol/L). In contrast, 8-OHdG serum levels were two-fold higher in patients after treatment (0.21±0.03ng/mL) than before treatment (0.11±0.02ng/mL) and three-fold higher than in controls (0.07±0.01ng/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.