title: Ochratoxin-induced toxicity, oxidative stress and apoptosis ameliorated by quercetin--modulation by Nrf2.
abstract: Ochratoxin (OTA) is one of the most abundant food contaminating mycotoxins and is commonly present in the food chain. Many of the effects associated with OTA, appear to be mediated through oxidative stress. Although the toxicity of OTA is fairly well characterized, antidotes for alleviating the toxicity are sparsely reported. Dietary antioxidants have gained much importance in the recent years for their antioxidative and therapeutic properties. In the present study the therapeutic strategy was directed towards use of quercetin, a dietary antioxidant to combat OTA-induced toxicity in Vero cell line. Our results demonstrate that quercetin pre-treatment suppressed OTA-induced cytotoxicity and oxidative stress. It modulated OTA-induced alteration on the antioxidant defence through activation of Nrf2 pathway. Morphological studies by scanning electron microscopy (SEM) and cell cycle analysis indicated that quercetin prevented OTA-induced apoptosis. It also inhibited the activation of caspase cascade that leads to DNA fragmentation. Quercetin also exhibited antigenotoxic potential by attenuating OTA-induced DNA damage and micronucleus (MN) formation. The results of the study demonstrate for the first time that quercetin pre-treatment prevents OTA-induced oxidative stress and apoptosis in Vero cell line.
authors.affiliation: Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641 046, Tamilnadu, India.
authors.forename: Periasamy
authors.initials: P
authors.lastname: Ramyaa
authors.forename: Viswanadha Vijaya
authors.initials: VV
authors.lastname: Padma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002522:Chlorocebus aethiops; D053938:DNA Fragmentation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015162:Micronucleus Tests; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D050050:Protein Carbonylation / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D014709:Vero Cells / Q000187:drug effects
chemical_list: D051267:NF-E2-Related Factor 2; D009793:Ochratoxins; D020011:Protective Agents; D009569:Nitric Oxide; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D002118:Calcium
keywords: 2,7-dichlorodihydrofluorescein diacetate; 2,7-dichlorofluorescein; 3,30-di-hexyloxacarbocyanine iodide; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ANOVA; AO/EB; ARE; Apoptosis; CAT; CBMN; CCCP; DAB; DCF; DCF-DA; DMEM; DMSO; DNA damage; DTT; DiOC6; EDTA; FBS; GPx; GSH; GST; IC20; LDH; LPO; LPS; MN; MNBNC; MTT; NF-κB; NO; Nrf-2; OPT; OTA; Ochratoxin; Oxidative stress; PARP; PCC; PMSF; Quercetin; ROS; SDS–PAGE; SEM; SOD; Scanning electron microscopy; [Ca(2+)](i); acridine orange/ethidium bromide; analysis of variance; antioxidant responsive element; carbonyl cyanide m-chlorophenylhydrazone; catalase; cytokinesis block micronucleus assay; diaminobenzidine; dimethyl sulfoxide; dithiothreitol; dulbecco’s modified eagle’s medium; ethylenediamine tetraacetic acid; fetal bovine serum; glutathione; glutathione S transferase; glutathione peroxidase; iNOS; inducible nitric oxide synthase; inhibitory concentration 20; intracellular calcium level; lactate dehydrogenase; lipid peroxidation; lipopolysaccharide; micronucleated binucleate cells; micronucleus; nitric oxide; nuclear factor E2 p45-related factor 2; nuclear factor-kappa B; ochratoxin; ortho-phthalaldehyde; phenyl methyl sulfonyl fluoride; poly (ADP-ribose) polymerase; protein carbonyl content; reactive oxygen species; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; superoxide dismutase