Effect of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine on oxidative stress and gene expression of c-fos, c-jun, p16 and Rb in rat colons and protective role of seabuckthorn seed oil

Abstract

Exposure to 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP), a typical example of heterocyclic amine compounds, increases colon cancer risk. Seabuckthorn (SBT) seed oil is a biologically active substance extracted from seeds of wild Hippophae rhamnoides L. Here, we sought to investigate the toxicological mechanisms underlying oxidative stress and cancer-related gene expression in the rat colons as well as the protective effect of SBT seed oil against colonic oxidative damage. Our results showed that PhIP significantly decreased the anti-oxidative enzyme activities whereas increased the malondialdehyde (MDA) contents, protein carbonyl (PCO) levels and DNA-protein cross-links (DPC) coefficients in the rat colons compared with the solvent-control group. Moreover, PhIP activated expression of c-fos and c-jun and inhibited p16 and Rb expression. Additionally, SBT seed oil plus PhIP significantly improved antioxidant markers and reduced the levels of MDA, PCO and DPC compared to those in rats exposed to PhIP alone. These data indicated that PhIP could induce oxidative stress and abnormal alterations of cancer-related gene expression in the rat colons while SBT seed oil may be beneficial because of its ability to alleviate the PhIP-induced oxidative damage to the rats.

Keywords:

• 2-Amino-1-methyl-6-phenylimidazo [4
• 5-b] pyridine
• seabuckthorn seed oil
• rat colon
• oxidative stress
• proto-oncogenes
• tumor suppressor genes