Blockage of both the extrinsic and intrinsic pathways of diazinon-induced apoptosis in PaTu cells by magnesium oxide and selenium nanoparticles

Abstract

Mahdi Shiri,1,2,* Mona Navaei-Nigjeh,1,3,* Maryam Baeeri,1 Mahban Rahimifard,1 Hossein Mahboudi,4 Ahmad Reza Shahverdi,5 Abbas Kebriaeezadeh,1 Mohammad Abdollahi1,6,7 1Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, 2School of Medicine, Artesh University of Medical Sciences, 3Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Biotechnology, Faculty of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, 6Toxicology Interest Group, USERN, 7Endocrinology & Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Diazinon (DZ) is an organophosphorus insecticide that acts as an acetylcholinesterase inhibitor. It is important to note that it can induce oxidative stress, lipid peroxidation, diabetic disorders, and cytotoxicity. Magnesium oxide (MgO) and selenium nanoparticles (Se NPs) showed promising protection against oxidative stress, lipid peroxidation, cytotoxicity, and diabetic disorders. Therefore, this study was conducted to explore the possible protective mechanisms of MgO and Se NPs against DZ-induced cytotoxicity in PaTu cell line. Cytotoxicity of DZ, in the presence or absence of effective doses of MgO and Se NPs, was determined in human pancreatic cancer cell line (PaTu cells) after 24 hours of exposure by using mitochondrial activity and mitochondrial membrane potential assays. Then, the insulin, proinsulin, and C-peptide release; caspase-3 and -9 activities; and total thiol molecule levels were assessed. Determination of cell viability, including apoptotic and necrotic cells, was assessed via acridine orange/ethidium bromide double staining. Furthermore, expression of 15 genes associated with cell death/apoptosis in various phenomena was examined after 24 hours of contact with DZ and NPs by using real-time polymerase chain reaction. Compared to the individual cases, the group receiving the combination of MgO and Se NPs showed more beneficial effects in reducing the toxicity of DZ. Cotreatment of PaTu cell lines with MgO and Se NPs counteracts the toxicity of DZ on insulin-producing cells. Keywords: apoptosis, diazinon, human pancreatic cancer cell line, organophosphorus, toxicity

Keywords

• Apoptosis
• Diazinon
• Human pancreatic cancer cell line
• Organophosphorus
• Toxicity