Gold Nanoparticles Perturb Drug-Metabolizing Enzymes and Antioxidants in the Livers of Male Rats: Potential Impact on Drug Interactions

Abstract

Mohammed YI Al-Hamadani,1 Abdullah M Alzahrani,2 Mokhtar I Yousef,3 Maher A Kamel,4 Wael M El-Sayed1 1Department of Zoology Faculty of Science, Ain Shams University, Cairo 11566, Egypt; 2Department of Biological Sciences, King Faisal University, Ahsaa, Saudi Arabia; 3Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt; 4Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, EgyptCorrespondence: Wael M El-Sayed Tel [phone]Fax [phone]Email [email protected] and Aim: With the wide applications of chitosan and gold nanoparticles in drug delivery and many consumer products, there is limited available information about their effects on drug-metabolizing enzymes (DMEs). Changes in DMEs could result in serious drug interactions. Therefore, this study aimed to investigate the effects of exposure to chitosan or gold nanoparticles on hepatic Phase I and II DMEs, liver function and integrity, oxidative damage and liver architecture in male rats.Methods: Animals were divided into three equal groups: a control group, a group treated with chitosan nanoparticles (200 mg/kg, 50± 5 nm) and a group treated with gold nanoparticles (4 mg/kg, 15± 5 nm). Rats were orally administered their respective doses daily for 10 days.Results: Both chitosan and gold nanoparticles decreased the body weights by more than 10%. Gold nanoparticles reduced the activities of antioxidants (superoxide dismutase and catalase), and reduced glutathione level and elevated the malondialdehyde level in the liver. Gold nanoparticles caused significant reductions in CYP1A1, CYP2E1, quinone oxidoreductase1, and glutathione S-transferase and elevated CYP2D6 and N-acetyl transferase2. Chitosan elevated CYP2E1 and CYP2D6 and reduced UDP-glucuronosyltransferase 1A1. Both nanoparticles disturbed the architecture of the liver, but the deleterious effects after gold nanoparticles treatment were more prominent.Conclusion: Taken together, gold nanoparticles severely perturbed the DMEs and would result in serious interactions with many drugs, herbs, and foods.Keywords: CYP450, chitosan, drug interactions, drug metabolizing enzymes, oxidative stress

Keywords

• cyp450
• chitosan
• drug interactions
• drug metabolizing enzymes
• oxidative stress