Lupeol, a triterpene, inhibits early responses of tumor promotion induced by benzoyl peroxide in murine skin.
The modulating effect of Lupeol [lup-20(29)-en-3 beta -ol], a triterpene found in many fruits and medicinal plants, on benzoyl peroxide-induced tumor promotion responses or tumor promotion in murine skin is described. Benzoyl peroxide is an effective cutaneous tumor promoter acting through the generation of oxidative stress, the induction of ornithine decarboxylase activity and the enhancement of DNA synthesis. Benzoyl peroxide treatment increases cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of the cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, is decreased and levels of cutaneous glutathione are depleted. Benzoyl peroxide treatment also induces ornithine decarboxylase activity and enhances [3H]thymidine uptake in DNA synthesis. Prophylactic treatment of mice with lupeol (0.75 and 1.5 mg per animal) 1 hour before benzoyl peroxide treatment resulted in a diminution of benzoyl peroxide-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P< 0.01 and P< 0.01, respectively). In addition, depleted levels of glutathione and inhibited activity of antioxidant enzymes were recovered to a significant level (P< 0.01, P< 0.05 and P< 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis were inhibited significantly (P< 0.05) in a dose-dependent manner. The protective effect of lupeol was dose dependent in all parameters. The results suggest that lupeol is an effective skin chemopreventive agent that may suppress benzoyl peroxide-induced cutaneous toxicity.
Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
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Saleem
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Alam
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Arifin
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Shah
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Ahmed
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Sultana
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001585:Benzoyl Peroxide / Q000037:antagonists & inhibitors; D002273:Carcinogens / Q000037:antagonists & inhibitors; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D053978:Pentacyclic Triterpenes; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D000094042:Lupanes
D000893:Anti-Inflammatory Agents; D001585:Benzoyl Peroxide; D002273:Carcinogens; D002374:Catalase; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; D009955:Ornithine Decarboxylase; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes