Hydroxytyrosol, a dietary phenolic compound forestalls the toxic effects of methylmercury-induced toxicity in IMR-32 human neuroblastoma cells

Abstract

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.

Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

“…Regarding the in vitro tests, which were performed in the last 10 years, oleuropein, HT, and Tyr, as well as more complex EVOO phenolic extracts, were evaluated in a broad variety of cell sorts. They resulted in being able to enhance Nrf-2 expression and consequently HO-1, γ-glutamyl-cysteinyl-ligase (γ-GCL), NQO1, GPx, TRX, SOD, and other antioxidant enzymes in LPS-treated macrophages [67,68], but also in different cancer cells [69][70][71][72][73] or normal cells, like retinal pigmented epithelium ARPE-19 cells [74], untreated or stimulated with pro-oxidant and pro-inflammatory stimuli.…”

Modulation of Nrf2 by Olive Oil and Wine Polyphenols and Neuroprotection

“…HT (5 µM) downregulated p53, bax, cytochrome C, and caspase 3, and upregulated Nrf2 and metallothionein. HT promotes the expression of Nrf2, which, in turn, elevates the expression of various cellular GSH/GST levels, thereby ameliorating the adverse effects of MeHg [ 110 ].…”

Nutritional Aspects of Food Toxicology: Mercury Toxicity and Protective Effects of Olive Oil Hydroxytyrosol

“…A recent study highlights the efficacy of HT in preventing MeHginduced neurotoxicity, using IMR-32 human neuroblastoma cells as a surrogate model for studying the effects of heavy metal on neuronal dysfunction. In this study, Mohan et al [82] report that cell preincubation with HT inhibits MeHg-induced cytotoxicity along with reduction of ROS formation and the maintenance of an efficient endogenous defence system, including GSH levels and superoxide dismutase and catalase activities. Furthermore, HT also prevents genotoxicity and apoptosis, causing downregulation of p53, bax, cytochrome c, and caspase 3 and upregulation of prosurvival proteins including Nrf2 and metallothionein.…”

“…In this respect, GSH enhancement may represent a key mechanism, as reported in different cellular systems. In particular, Mohan et al [82] report that the ability of HT to promote the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which in turn elevates GSH levels, is crucial in ameliorating the neurotoxic effect of MeHg, as discussed in the next paragraph. Figure 6: HT prevents PS exposure and GSH depletion in human RBC.…”

“…Finally, HT ameliorates acrolein-induced cytotoxicity in retinal pigment epithelial cells, showing a protection from oxidative damage and mitochondrial dysfunction [78] and reduces acrylamideinduced cytotoxicity, preventing DNA damage and intracellular ROS formation in HepG2 cells [79]. In the last few years, several papers report data indicating that this dietary component is able to counteract the toxic effects linked to exposure of heavy metals, including Hg [80][81][82].…”