Resveratrol Dose-Dependently Protects the Antioxidant Mechanism of Hydrogen Peroxide-Exposed Healthy Cells and Lung Cancer Cells

Year 2024, , 42 - 49, 30.05.2024

Öznur Yurdakul , Aysun Özkan

https://doi.org/10.26650/EurJBiol.2024.1395956

Abstract

Objective: The objective of this study was to investigate the protective effects and the underlying mechanisms of resveratrol against hydrogen peroxide (H2O2 )-induced oxidative stress in healthy human and lung cancer cells.
Materials and Methods: The cytotoxic doses and IC50 values of resveratrol and hydrogen peroxide for cells were determined by the Cell Titer Blue-Viability Assay kit. The amount of malondialdehyde (MDA) was determined by fluorescence spectrophotometer. The amount of intracellular reduced glutathione level and antioxidant enzyme activities were analyzed by spectrophotometric methods.
Results: In both cells, H2O2 treatment alone (IC50 and IC50) increased MDA, glutathione reductase, glutathione S-transferase, selenium-dependent glutathione peroxidase and non-selenium-dependent glutathione peroxidase activities, but glutathione levels decreased compared to the H2O + 2 resveratrol treatment. In addition, high doses of resveratrol alone (IC50 and IC70) induced more oxidative stress in cancer cells than in healthy cells. High doses of resveratrol alone (IC50 and IC70) also showed cytotoxic effects in cells and decreased cell viability. Resveratrol caused more cytotoxic effects in cancer cells compared to healthy cells.
Conclusion: The results of this study show that the increase in MDA level and antioxidant enzyme activity caused by highdose resveratrol treatment reveals the prooxidant effect of resveratrol. Our results also showed an antioxidant effect by reducing oxidative stress in cells pre-incubated with low-dose resveratrol and then exposed to H2O2 . Resveratrol has a dose-dependent biphasic (pro/antioxidant) effect on the antioxidant mechanism of cells. However, more research is needed to confirm this

Keywords

Antioxidant enzymes, resveratrol, dose-dependent toxicity, hydrogen peroxide

Ethical Statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Supporting Institution

Akdeniz University

Project Number

2014.02.0121.009

Thanks

This work was supported by [Akdeniz University] (Grant numbers [2014.02.0121.009]). Author Öznur Yurdakul and Aysun Özkan have received research support from the Scientific Research Projects Commission.

References

• Archile-Contreras AC, Purslow PP. Oxidative stress may affect meat quality by interfering with collagen turnover by muscle fibroblasts. Food Res Int. 2011;44(2):582-588. google scholar
• Polawska E, Bagnicka AW, Niemczuk K, Lipinska JO. Relations between the oxidative status, mastitis, milk quality and disorders of reproductive functions in dairy cows—A review. Anim Sci Pap Rep. 2012;30(4):297-307. google scholar
• Cap M, Vachova L, Palkova Z. Reactive oxygen species in the signaling and adaptation of multicellular microbial communities. Oxid Med Cell Longev. 2012;2012:976753. doi:10.1155/2012/976753 google scholar
• Descalzo AM, Sancho AM. A review of natural antioxidants and their effects on oxidative status, odor and quality of fresh beef produced in Argentina. Meat Sci. 2008;79(3):423-436. google scholar
• Acharya A, Das I, Chandhok D, Saha T. Redox regulation in cancer: A double-edged sword with therapeutic potential. Oxid Med Cell Longev. 2010;3:702528. doi:10.4161/oxim.3.1.10095 google scholar
• Rogers LK, Cismowski MJ. Oxidative stress in the lung-The essential paradox. Curr Opin Toxicol. 2018;7:37-43. google scholar
• Valavanidis A, Vlachogianni T, Fiotakis K, Loridas S. Pul-monary oxidative stress, inflammation and cancer: Respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mecha-nisms. Int J Environ Res Public Health. 2013;10(9):3886-3907. google scholar
• Boukhenouna S, Wilson MA, Bahmed K, Kosmider B. Reactive oxygen species in chronic obstructive pulmonary disease. Oxid Med Cell Longev. 2018;5730395. doi:10.1155/2018/5730395. google scholar
• Amintas S, Dupin C, Boutin J, et al. Bioactive food components for colorectal cancer prevention and treatment: A good match. Crit Rev Food Sci Nutr. 2023;63(23):6615-6629. google scholar
• Sugahara Y, Ohta T, Taguchi Y, et al. Resveratrol deriva-tive production by high-pressure treatment: proliferative in-hibitory effects on cervical cancer cells. Food Nutr Res. 2022;66. doi:10.29219/fnr.v66.7638 google scholar
• Aminzare M, Moniri R, Hassanzad Azar H, Mehrasbi MR. Evaluation of antioxidant and antibacterial interactions between resveratrol and eugenol in carboxymethyl cellulose biodegrad-able film. Food Sci Nutr. 2022;10(1):155-168. google scholar
• Wijekoon C, Netticadan T, Siow YL, et al. Potential associations among bioactive molecules, antioxidant activity and resveratrol production in vitis vinifera fruits of North America. Molecules. 2022;27(2):336. doi:10.3390/molecules27020336. google scholar
• Yi J, He Q, Peng G, Fan Y. Improved water solubility, chem-ical stability, antioxidant and anticancer activity of resveratrol via nanoencapsulation with pea protein nanofibrils. Food Chem. 2022;377:131942. doi:10.1016/j.foodchem.2021.131942. google scholar
• Mukherjee S, Dudley JI, Das DK. Dose-dependency of resvera-trol in providing health benefits. Dose Response. 2010;8(4):478-500. google scholar
• Zhang L-X, Li C-X, Kakar MU, et al. Resvera-trol (RV): A pharmacological review and call for fur-ther research. Biomed Pharmacother. 2021;143:112164. doi:10.1016/j.biopha.2021.112164. google scholar
• Salehi B, Mishra AP, Nigam M, et al. Resveratrol: A double-edged sword in health benefits. Biomedicines. 2018;6(3):91. doi:10.3390/biomedicines6030091 google scholar
• Wasowicz W, Neve J, Peretz A. Optimized steps in fluoromet-ric determination of thiobarbituric acid-reactive substances in serum: Importance of extraction pH and influence of sample preservation and storage. Clinical Chem. 1993;39(12):2522-2526. google scholar
• Bradford MM. A rapid and sensitive method for the quantita-tion of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254. google scholar
• Habig WH, Jakoby WB. Assays for differentiation of glutathione S-transferases. Methods Enzymol. 1981;77:398-405. google scholar
• Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol. 1985;113:484-490. google scholar
• Paglia DE, Valentine WN. Studies on the quantitative and qual-itative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158-169. google scholar
• Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun. 1976;71(4):952-958. google scholar
• Beutler E. Glutathione peroxidase. In: Red cell metabolism: A manual of biochemical methods. Grune & Stratton. 1975:71-73. google scholar
• SPSS. IBM SPSS Statistics for Windows. IBM Corp. google scholar
• Lee W, Lee DG. Resveratrol induces membrane and DNA dis-ruption via pro-oxidant activity against Salmonella typhimurium. Biochem Biophys Res Commun. 2017;489(2):228-234. google scholar
• Bade BC, Dela Cruz CS. Lung cancer 2020: Epidemiology, etiology, and prevention. Clin Chest Med. 2020;41(1):1-24. google scholar
• Sharifi-Rad M, Anil Kumar NV, Zucca P, et al. Lifestyle, ox-idative stress, and antioxidants: Back and Forth in the patho-physiology of chronic diseases. Front Physiol. 2020;11:694. doi:10.3389/fphys.2020.00694 google scholar
• Bosutti A, Degens H. The impact of resveratrol and hydrogen peroxide on muscle cell plasticity shows a dose-dependent inter-action. Sci Rep. 2015;5(1):8093. doi:10.1038/srep08093 google scholar
• Yang L, Yang L, Tian W, et al. Resveratrol plays dual roles in pan-creatic cancer cells. J Cancer Res Clin Oncol. 2014;140(5):749-755. google scholar
• Singh CK, Ndiaye MA, Ahmad N. Resveratrol and can-cer: Challenges for clinical translation. Biochim Biophys Acta. 2015;1852(6):1178-1185. google scholar
• Pandey KB, Rizvi SI. Protective effect of resveratrol on for-mation of membrane protein carbonyls and lipid peroxidation in erythrocytes subjected to oxidative stress. Appl Physiol Nutr Metab. 2009;34:1093-1097. google scholar
• Chen C, Jiang X, Zhao W, Zhang Z. Dual role of resveratrol in modulation of genotoxicity induced by sodium arsenite via oxidative stress and apoptosis. Food Chem Toxicol. 2013;59:8-17. google scholar
• Spanier G, Xu H, Xia N, et al. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of super-oxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol. 2009;60(4):111-116. google scholar
• Yen GC, Duh PD, Lin CW. Effects of resveratrol and 4-hexylresorcinol on hydrogen peroxide-induced oxidative DNA damage in human lymphocytes. Free Radic Res. 2003;37(5):509-514. google scholar
• Zhang X, Liu X, Wan F, et al. Protective effect of resver-atrol against hydrogen peroxide-induced oxidative stress in bovine skeletal muscle cells. Meat Science. 2022;185:108724. doi:10.1016/j.meatsci.2021.108724 google scholar
• Konyalioglu S, Armagan G, Yalcin A, Atalayin C, Dagci T. Effects of resveratrol on hydrogen peroxide-induced oxida-tive stress in embryonic neural stem cells. Neural Regen Res. 2013;8(6):485-495. google scholar
• Fukui M, Choi HJ, Zhu BT. Mechanism for the protective effect of resveratrol against oxidative stress-induced neuronal death. Free Radic Biol Med. 2010;49(5):800-813. google scholar