Topically applied vitamin E prevents massive cutaneous inflammatory and oxidative stress responses induced by double application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice

Chem Biol Interact. 2008 Apr 15;172(3):195-205. doi: 10.1016/j.cbi.2007.11.017. Epub 2008 Jan 4.

Abstract

Vitamin E (alpha-tocopherol) is a promising chemopreventive and pharmacologically safe agent, which can be exploited or tested against skin cancer. It is an established antioxidant with an ability to ameliorate the UV-induced skin damage and chemically induced inflammation in lungs. However, there are some conflicting reports about its role as a modulator of chemically induced promotion. We evaluated its efficacy in preventing the inflammatory and oxidative stress responses in a double 12-O-tetradecanoylphorbol-13-acetate (TPA) application tumor skin promotion protocol. Double application of TPA was undertaken to produce massive inflammatory and oxidative stress responses. Topical TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion. Vitamin E application 30 min prior to TPA treatment (10 nmol) inhibited induction of hydrogen peroxide, myeloperoxidase (MPO) activity, xanthine oxidase (XO) activity and lipid peroxidation (LPO). Vitamin E also positively modulated altered antioxidants of mouse skin. Histological examination also revealed marked improvement. These results confirm the efficacy of vitamin E against early inflammatory and oxidative stress responses, which are hallmark of tumor promotion and provide rational basis for chemopreventive action of vitamin E in skin cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / pharmacokinetics
  • Antioxidants / therapeutic use
  • Dermatitis / etiology
  • Dermatitis / prevention & control*
  • Female
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / metabolism
  • Lipid Peroxidation / drug effects*
  • Lipid Peroxidation / physiology
  • Mice
  • Mice, Inbred SENCAR
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Peroxidase / antagonists & inhibitors
  • Peroxidase / metabolism
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / prevention & control
  • Tetradecanoylphorbol Acetate / adverse effects*
  • Vitamin E / therapeutic use*
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Vitamin E
  • Hydrogen Peroxide
  • Peroxidase
  • Xanthine Oxidase
  • Tetradecanoylphorbol Acetate