Hydroxytyrosol, a dietary phenolic compound forestalls the toxic effects of methylmercury-induced toxicity in IMR-32 human neuroblastoma cells.
This study demonstrates the protective potential of hydroxytyrosol (HT), an olive oil phenol, against methylmercury (MeHg)-induced neurotoxicity using IMR-32 human neuroblastoma cell line. HT inhibited MeHg-induced cytotoxicity and genotoxicity as confirmed by MTT, micronucleus, and comet assays. Cells preconditioned with HT showed reduction of MeHg-induced cellular oxidative stress along with the maintenance of glutathione, superoxide dismutase, glutathione-S-tranferase, and catalase. Fluorescence microscopy and DNA ladder assays indicated the inhibitory effect of HT against MeHg-induced apoptosis, which was further established by Western blotting. An effective concentration of 5 µM HT caused downregulation of p53, bax, cytochrome c, and caspase 3 and upregulation of prosurvival proteins including nuclear factor erythroid 2-related factor 2 (Nrf2) and metallothionein. This work indicates the cytoprotective potential of HT against MeHg-induced toxicity primarily by the lowering of oxidative stress, which may be endorsed to its antigenotoxic and antiapoptotic potential, in addition to its free radical scavenging ability. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1264-1275, 2016.
Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, 576 104, Karnataka, India.
Vishnu
V
Mohan
Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, 576 104, Karnataka, India.
Shubhankar
S
Das
Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, 576 104, Karnataka, India.
Satish B S
SB
Rao
D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C005975:3,4-dihydroxyphenylethanol; D045304:Cytochromes c; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione; D010626:Phenylethyl Alcohol
apoptosis; hydroxytyrosol; methylmercury; oxidative stress