Effects of Oral Isotretinoin on Skin and Serum Levels of FoxO3, TRAIL and p53 and Metabolic Parameters.

Objectives: Isotretinoin-mediated apoptosis is considered the main cause of anti-acne side effects of isotretinoin. The aim of this study is to investigate the effects of oral isotretinoin therapy on the skin and serum levels of forkhead box transcription factor (FoxO)-3, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), p53 and metabolic parameters and examine the relationship between these parameters.

Methods: Sixteen acne vulgaris patients who were administered the appropriate cumulative dose of oral isotretinoin were enrolled in this prospective study.

Results: The decreases in the values of body mass index, waist circumference, systolic blood pressure (BP), CRP, and ferritin from the baseline to the end of the treatment were statistically significant (p=0.028, p=0.029, p=0.008, p=0.046, and p=0.003, respectively). The increases in the levels of serum low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), total cholesterol, gamma-glutamyl transferase (GGT), and FoxO3 from the baseline to the end of the treatment were statistically significant (p=0.001, p=0.004, p<0.001, p=0.010, p=0.007, respectively). In terms of changes from the baseline to the end of the treatment, serum FoxO3 levels were positively correlated with the changes in serum TRAIL levels (r=0.674, p=0.004). The changes in serum FoxO3 levels were positively correlated with the changes in fasting blood glucose levels (r=0.540, p=0.031). The changes in serum TRAIL levels were positively correlated with the changes in the values of systolic BP (r=0.552, p=0.027) and diastolic BP (r=0.511, p=0.043). The changes in serum p53 levels and serum LDL-C levels were also positively correlated (r=0.499, p=0.049).

Conclusion: Isotretinoin therapy caused an increase in skin and serum levels of FoxO3 and TRAIL and a decrease in serum and skin p53 values. However, only the increase in serum FoxO3 levels was statistically significant. The observed reduction in p53 levels implies that the isotretinoin-related side effects may not rely on p53-mediated apoptosis, and it may be considered that its safety profile is better than expected. The correlations between the changes during isotretinoin therapy in metabolic parameters and TRAIL, p53, and FoxO3 values suggest that isotretinoin's metabolic side effects may involve these molecules.