Curcumin and resveratrol in combination modulate drug-metabolizing enzymes as well as antioxidant indices during lung carcinogenesis in mice

Hum Exp Toxicol. 2015 Jun;34(6):620-7. doi: 10.1177/0960327114551396. Epub 2015 Jan 29.

Abstract

This study investigated combined chemopreventive potential of curcumin and resveratrol during benzo(a)pyrene (BP)-induced lung carcinogenesis in mice. The mice were segregated into five groups that included normal control, BP-treated, BP + curcumin-treated, BP + resveratrol-treated, and BP + curcumin + resveratrol-treated groups. A statistically significant increase in the levels of lipid peroxidation (LPO) was observed in the lungs of mice after 22 weeks of single dose of benzo(a)pyrene. Further, BP treatment also resulted in a significant increase in the enzyme activities of aryl hydrocarbon hydroxylase as well as drug-metabolizing enzymes, namely cytocrome P450 and cytochrome b5. On the other hand, reduced glutathione (GSH) levels, the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione-S-transferase (GST) were found to be significantly decreased following BP treatment. Supplementation with curcumin and resveratrol to BP-treated mice significantly decreased the LPO levels, GSH levels, and enzyme activities of drug-metabolizing enzymes. Further, treatment of curcumin and resveratrol to BP-treated mice significantly elevated the activities of SOD, GR, and GST. Histoarchitectural studies showed well-differentiated signs of lung carcinogenesis following BP administration to mice. However, combined treatment with curcumin and resveratrol resulted in a noticeable improvement in the lung histoarchitecture. This study, therefore, concludes that curcumin and resveratrol when supplemented in combination regulate drug-metabolizing enzymes as well as antioxidant enzymes during lung carcinogenesis in mice.

Keywords: Curcumin; cytochromes; lung cancer; phytochemicals; resveratrol.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Benzo(a)pyrene / toxicity*
  • Carcinogens / toxicity*
  • Catalase / metabolism
  • Curcumin / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytochromes b5 / metabolism
  • Glutathione / metabolism
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / metabolism
  • Lipid Peroxidation / drug effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Resveratrol
  • Stilbenes / pharmacology*
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Carcinogens
  • Stilbenes
  • Benzo(a)pyrene
  • Cytochromes b5
  • Cytochrome P-450 Enzyme System
  • Catalase
  • Aryl Hydrocarbon Hydroxylases
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione Transferase
  • Glutathione
  • Curcumin
  • Resveratrol