Modulation of collagen synthesis and its gene expression in human skin fibroblasts by tocotrienol-rich fraction

INTRODUCTION: Skin aging may occur as a result of increased free radicals in the body. Vitamin E, the major chain-breaking antioxidant, prevents propagation of oxidative stress, especially in biological membranes. In this study, the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing oxidative stress-induced skin aging was evaluated by determining the rate of total collagen synthesis and its gene expression in human skin fibroblasts. MATERIAL AND METHODS: Primary culture of human skin fibroblasts was derived from circumcision foreskin of 9 to 12 year-old boys. Fibroblast cells were divided into 5 different treatment groups: untreated control, hydrogen peroxide (H(2)O(2))-induced oxidative stress (20 µM H(2)O(2) exposure for 2 weeks), TRF treatment, and pre- and post-treatment of TRF to H(2)O(2)-induced oxidative stress. RESULTS: Our results showed that H(2)O(2)-induced oxidative stress decreased the rate of total collagen synthesis and down-regulated COL I and COL III in skin fibroblasts. Pre-treatment of TRF protected against H(2)O(2)-induced oxidative stress as shown by increase in total collagen synthesis and up-regulation of COL I and COL III (p<0.05) genes. However, similar protective effects against H(2)O(2)-induced oxidative stress were not observed in the post-treated fibroblasts. CONCLUSIONS: Tocotrienol-rich fraction protects against H(2)O(2)-induced oxidative stress in human skin fibroblast culture by modulating the expression of COL I and COL III genes with concomitant increase in the rate of total collagen synthesis. These findings may indicate TRF protection against oxidative stress-induced skin aging.