title: Hepatotoxic effect of ochratoxin A and citrinin, alone and in combination, and protective effect of vitamin E: In vitro study in HepG2 cell.
abstract: Ochratoxin A (OTA) and citrinin (CTN) are the most commonly co-occurring mycotoxins in a wide variety of food and feed commodities. The major target organ of these toxins is kidney but liver could also be a target organ. The combined toxicity of these two toxins in kidney cells has been studied but not in liver cell. In this study HepG2 cells were exposed to OTA and CTN, alone and in combination, with a view to compare the molecular and cellular mechanisms underlying OTA, CTN and OTA + CTN hepatotoxicity. OTA and CTN alone as well as in combination affected the viability of HepG2 cells in a dose-dependent manner. OTA + CTN, at a dose of 20% of IC50 of each, produced effect almost similar to that produced by either of the toxins at its IC50 concentration, indicating that the two toxins in combination act synergistically. The cytotoxicity of OTA + CTN on hepatocytes is mediated by increased level of intracellular ROS followed/accompanied by DNA strand breaks and mitochondria-mediated intrinsic apoptosis. Co-treatment of vitamin E (Vit E) with OTA, CTN and OTA + CTN reduced the levels of ROS and the cytotoxicity. But the genotoxic effect of OTA and OTA + CTN was not completely alleviated by Vit E treatment whereas the DNA damage as caused by CTN when treated alone was obviated, indicating that OTA induces DNA damage directly whereas CTN induces ROS-mediated DNA damage and OTA + CTN combination induces DNA damage not exclusively relying on but influenced by ROS generation. Taken together, these findings indicate that OTA and CTN in combination affect hepatocytes at very low concentrations and, thereby, pose a potential threat to public and animal health.
authors.affiliation: Department of Microbiology, Bharathidasan University, Tiruchirappalli 620024, India; Mahatma Gandhi-Doerenkamp Center, Bharathidasan University, Tiruchirappalli 620024, India.
authors.forename: Loganathan
authors.initials: L
authors.lastname: Gayathri
authors.affiliation: Mahatma Gandhi-Doerenkamp Center, Bharathidasan University, Tiruchirappalli 620024, India.
authors.forename: Rajakumar
authors.initials: R
authors.lastname: Dhivya
authors.affiliation: Department of Microbiology, Bharathidasan University, Tiruchirappalli 620024, India.
authors.forename: Dharumadurai
authors.initials: D
authors.lastname: Dhanasekaran
authors.affiliation: Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Vaiyapuri S
authors.initials: VS
authors.lastname: Periasamy
authors.affiliation: Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
authors.affiliation: Mahatma Gandhi-Doerenkamp Center, Bharathidasan University, Tiruchirappalli 620024, India; Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia. Electronic address: mgdcaua@yahoo.in.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Akbarsha
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002274:Carcinogens, Environmental / Q000737:chemistry / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002953:Citrinin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D005506:Food Contamination; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D009793:Ochratoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002274:Carcinogens, Environmental; D009153:Mutagens; D009793:Ochratoxins; D017382:Reactive Oxygen Species; D014810:Vitamin E; C025589:ochratoxin A; D002953:Citrinin
keywords: Citrinin; Hepatotoxicity; Mycotoxin; Ochratoxin A; Reactive oxygen species