抄録
[Introduction] The growing exposure of the human and animals to heavy metal pollution generates modulation in xenobiotics-metabolizing enzymes (XMEs) response. In this study, the modulation of Ahr ligand-dependent toxicities by heavy metals and the molecular basis of this modulation were investigated.
[Materials and Methods] Samples were collected from different edible offal of cattle slaughtered at Zagazig abattoir, Egypt. Different heavy metals were measured using atomic absorption spectrophotometer. Human and rat liver hepatoma cell lines (HEPG2 and H4IIE) were treated with Lead and Copper under different concentrations ranged between permissible and toxic doses. The effects of these treatments on various XMEs and regulatory elements were screened using the methods of qPCR and Western Blotting.
[Results and Discussion] Liver, kidney and tongue showed the highest contents of the various heavy metal residues compared to other tissues. Lead, copper, cadmium, zinc and nickel exceeded the maximum permissible limits of Egyptian Standards and WHO. Interestingly, both copper and lead could induce CYP1A1 mRNA expression under low doses in the treated cell cultures. This expression level was markedly decreased under high concentrations. Effects of copper and lead on CYP1A1 expression was parallel to their effects on Ahr suggesting that those effects were in response to Ahr. All tested phase II enzymes were severely down regulated by exposure to lead in a concentration dependent manner. In conclusion, there were clear cross-talks between copper, lead and pase I, II enzymes and regulatory elements in the cultured cells.
