cytochrome-c-t and 3-4-dihydroxyphenylethanol

The present study reports beneficial effect of hydroxytyrosol (HT) against arsenic (As)-induced oxidative stress in the rat brain. Rats were orally administered with sodium arsenite dissolved in distilled water (25 ppm, by oral gavage) for 8 weeks or HT (10 mg/kg b. wt.) in combination with As. Results showed increase in protein oxidation and lipid peroxidation, while catalase and superoxide dismutase (SOD) activities as well as GSH content were decreased after As exposure in rat brain. Fourier transform infrared analysis showed significant alteration in peak area values that also validated the oxidative damage to lipids and proteins. In addition, As exposure caused increase in protein expression of caspase-3 and Bax, while Bcl-2 expression was downregulated resulting in translocation of cytochrome c from mitochondria to cytosol. Treatment of HT with As reversed protein oxidation, lipid peroxidation, and increased GSH content as well as catalase and SOD activities. Administration of HT also prevented translocation of cytochrome c from mitochondria and increased mitochondria/cytosol ratio of cytochrome c. Hence, treatment of HT with As improved antioxidant system and efficiently lowered the generation of oxidative stress in rat brain.

Topics: Administration, Oral; Animals; Antioxidants; Arsenites; Blotting, Western; Brain; Caspase 3; Catalase; Cytochromes c; Cytosol; Down-Regulation; Glutathione; Lipid Metabolism; Lipid Peroxidation; Male; Mitochondria; Nerve Tissue Proteins; Oxidative Stress; Phenylethyl Alcohol; Protein Transport; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar; Sodium Compounds; Spectroscopy, Fourier Transform Infrared; Superoxide Dismutase

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.

Topics: bcl-2-Associated X Protein; Caspase 3; Catalase; Cell Line, Tumor; Cell Survival; Comet Assay; Cytochromes c; DNA Fragmentation; Glutathione; Humans; Methylmercury Compounds; Microscopy, Fluorescence; Neuroblastoma; NF-E2-Related Factor 2; Oxidative Stress; Phenylethyl Alcohol; Superoxide Dismutase; Tumor Suppressor Protein p53