Isotretinoin therapy induces DNA oxidative damage.
BACKGROUND
Isotretinoin (Iso) is currently indicated for the treatment of cystic acne (CA) and is related to marked teratogenicity.


OBJECTIVE
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.


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.
Georgala
Sophia
S
Dermatological Clinic, University of Athens, School of Medicine, A. Syngros Hospital, Athens, Greece.
Papassotiriou
Ioannis
I
Georgala
Catherina
C
Demetriou
Elisabeth
E
Schulpis
Kleopatra H
KH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects*; D008099:Liver / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009135:Muscular Diseases / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*
D000975:Antioxidants; D003879:Dermatologic Agents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015474:Isotretinoin; D003849:Deoxyguanosine