Omega-3 fatty acids (EPA/DHA) act as a natural antioxidant to alleviate cadmium-induced oxidative stress and restore the oxidation/antioxidant balance in male Wistar mice
Main Article Content
Keywords
antioxidant; biochemical profile; cadmium toxicity; omega-3 fatty acids
Abstract
Omega-3 fatty acids are primarily derived from marine and plant sources and are commonly found in fatty fish and fish oils. The present study aimed to evaluate the in vivo antioxidant properties of omega-3 EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) and to investigate the effectiveness of exogenous omega-3 fatty acids in mitigating cadmium-induced oxidative stress. The experimental mice were allotted into four groups (n = 20), designated as untreated control, omega-3-treated, cadmium-exposed, and cadmium–omega-3 groups. The hematological and biochemical assays were performed to achieve the study’s aim. Both hematological and biochemical profiles of cadmium-exposed mice (Group 3) manifested significant alterations, including increments and decrements, compared to that of untreated control mice. Concerning the biochemical profile (serum profile), group 2 animals (omega-3-treated group) demon-strated no significant changes, compared to the untreated control. Mice in group 4 (cadmium-exposed and omega-3-accessed) exhibited increased levels of total proteins, a significant increase in the levels of antioxi-dant markers, such as total thiols, glutathione, total antioxidant capacity, superoxide dismutase, glutathione peroxidase, and catalase, and a significant decrease in the levels of blood cadmium, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen, urea, bilirubin, and oxidation markers (hydrogen peroxide and malondialdehyde), compared to the animals exposed to cad-mium (group 3). Tissue homogenates of the liver and kidney prepared from group 3 animals demonstrated parallel results to that revealed by serum biochemical analysis. It was concluded that omega-3 fatty acids (EPA/DHA) possess efficient antioxidant properties that effectively help to attenuate the oxidative stress induced by cadmium.
References
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Nichole, C., Ying, Z., Marian, N. and Fereidoon, S. 2008. Antioxidant activity and water-holding capacity of canola protein hydrolysates. Food Chem. 109:144–148. https://doi.org/10.1016/j.foodchem.2007.12.039
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Sharma, H., Rawal, N. and Mathew, B.B. 2015. The characteristics, toxicity, and effects of cadmium. Int J Nanotech Nanosci. 3:1–9.
Smith, G.I., Atherton, P., Reeds, D.N., Mohammed, B.S., Rankin, D., et al. 2011. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr. 93(2):402–412. https://doi.org/10.3945/ajcn.110.005611
Soleimani, A., Taghizadeh, M., Bahmani, F., Badroj, N. and Asemi, Z. 2017. Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial. Clin Nut. 36(1):79–84. https://doi.org/10.1016/j.clnu.2015.11.003
Staudacher, V., Trujillo, M., Diederichs, T., Dick, T.P. and Radi, R. 2018. Redox-sensitive GFP fusions for monitoring the catalytic mechanism and inactivation of peroxiredoxins in living cells. Redox Biol. 14:549–556. https://doi.org/10.1016/j.redox.2017.10.017
Tantipaiboonwong, P., Chaiwangyen, W., Suttajit, M., Kangwan, N., Kaowinn, S, Khanaree, C, Punfa, W. and Pintha, K. 2021. Molecular mechanism of antioxidant and anti-inflammatory effects of omega-3 fatty acids in perilla seed oil and rosmarinic acid rich fraction extracted from perilla seed meal on TNF-α induced A549 lung adenocarcinoma cells. Molecules. 26:6757. https://doi.org/10.3390/molecules26226757
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Yong, S., Lulu, W., Ying, W., Xiaqian, O. and Zhaoyuan, S. 2017. Purification and identification of a natural antioxidant protein from fertilized eggs. Korea J Food Sci Anim Resour. 37:764–772. https://doi.org/10.5851/kosfa.2017.37.5.764
Anderson, E.J., Thayne, K.A., Harris, M., Shaikh, S.R., Darden, T.M., Lark, D.S., Williams, J.M., Chitwood, W.R., Kypson, A.P. and Rodriguez, E. 2014. Do fish oil omega-3 fatty acids enhance antioxidant capacity and mitochondrial fatty acid oxidation in human atrial myocardium via PPARγ activation? Antioxid Redox Signal. 21(8):1156–1163. https://doi.org/10.1089/ars.2014.5888
Ateya, A.M., Sabri, N.A., El Hakim, I. and Shaheen, S.M. 2022. Effect of omega-3 fatty acids on serum lipid profile and oxidative stress in pediatric patients on regular hemodialysis: a randomized placebo-controlled study. J Renal Nut. 27:169–174. https://doi.org/10.1053/j.jrn.2016.11.005
Ayat, F., Said, F.H., Hoda, A.A., Kamel, A.A., Iwona, G., Witold, M. and Ibrahim, E. 2024. Antioxidant and antibacterial activities of omega-3 rich oils/curcumin nanoemulsions loaded in chitosan and alginate-based microbeads. Int J Biol Macro. 140:682–696. https://doi.org/10.1016/j.ijbiomac.2019.08.085
Benharrat, L.I., Senouci, A., Benhabib, W. and Mekki, K. 2022. Omega 3 supplementation improves inflammation and antioxidant defense in women with polycystic ovary syndrome. Curr Nutr Food Sci. 18(2):193–200. https://doi.org/10.2174/1573401317666211104121725
Case, A.J. 2017. On the origin of superoxide dismutase: an evolutionary perspective of superoxide-mediated redox signaling. Antioxidants (Basel). 6(4):82. https://doi.org/10.3390/antiox6040082
de Mattos, A.M., da Costa, J.A.C., Jordão, J., A.A. and Chiarello, P.G. 2017. Omega-3 fatty acid supplementation is associated with oxidative stress and dyslipidemia, but does not contribute to better lipid and oxidative status on hemodialysis patients. J. Renal Nut. 27(5):333–339. https://doi.org/10.1053/j.jrn.2017.02.006
Detopoulou, P., Voulgaridou, G., Saridaki, A.S., Argyris E-M. , Seva, V., Dedes, V., Giaginis C., et al. 2024. Omega-3 fatty acids' supplementation in Parkinson's disease: a systematic review of randomized controlled trials. Clin Nut Open Sci. 55:102–115. https://doi.org/10.1016/j.nutos.2024.03.007
Dorta, D.J., Leite, S., McMarco, K.C., Prado, M.R. and Rodrigues, T.A. 2003. Proposed sequence of events for cadmium-induced mitochondrial impairment. J Inorg Biochem. 97:251–257. https://doi.org/10.1016/S0162-0134(03)00314-3
Fazelian, S., Moradi, F., Agah, S., Hoseini, A., Heydari, H., Morvaridzadeh, M., Omidi, A., Pizarro, A.B., Ghafouri, A. and Heshmati, J. 2021. Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol. 22(1):160. https://doi.org/10.1186/s12882-021-02351-9
Feng, P., Chen, W. and Lin, H. 2016. Identifying antioxidant proteins by using optimal dipeptide compositions. Interdiscipl Sci Comput Life Sci. 8:186–191. https://doi.org/10.1007/s12539-015-0124-9
Feng, P., Ding, H., Lin, H. and Chen, W. 2017. AOD: the antioxidant protein database. Sci Rep. 7:7449. https://doi.org/10.1038/s41598-017-08115-6
Ghadiri, A.S.M., Ahmadi, M. and Shahidi, S.A. 2023. Preparation, characterization, and antioxidant activity of nanoliposomes-encapsulated turmeric and omega-3. Food Measure. 17:2697–2707. https://doi.org/10.1007/s11694-022-01785-5
Hajianfar, H., Paknahad, Z. and Bahonar, A. 2013. The effect of omega-3 supplements on antioxidant capacity in patients with type 2 diabetes. Int J Prev Med. 4(Suppl 2):S234–S238.
Heshmati, J., Morvaridzadeh, M., Maroufizadeh, S., Akbari, A., Yavari, M., Amirinejad, A., Maleki-Hajiagha, A. and Sepidarkish, M. 2019. Omega-3 fatty acids supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Pharmacol Res. 149:104462. https://doi.org/10.1016/j.phrs.2019.104462
Huang, W., Deng, Q., Xie, B., Shi, J. and Huang, F. 2009. Purification and characterization of an antioxidant protein from Grigo biloba seeds. Food Res Int. 43:86–94. https://doi.org/10.1016/j.foodres.2009.08.015
Klaudia, J. and Marian, V. 2011. Advances in metal-induced oxidative stress and human disease. Toxicology. 253:65–87. https://doi.org/10.1016/j.tox.2011.03.001.
Klaus, A. and Heribert, H. 2004. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol. 55:373–399. https://doi.org/10.1146/annurev.arplant.55.031903.141701
Mazereeuw, G., Herrmann, N., Andreazza, A.C., Scola, G., David, W.L., Paul, I.O. and Lanctôt, K.L. 2017. Oxidative stress predicts depressive symptom changes with omega-3 fatty acid treatment in coronary artery disease patients. Brain Behav Immun. 60:136–141. https://doi.org/10.1016/j.bbi.2016.10.005
Meital, L.T., Windsor, M.T., Perissiou, M. et al. 2019. Omega-3 fatty acids decrease oxidative stress and inflammation in macrophages from patients with small abdominal aortic aneurysm. Sci Rep. 9:12978. https://doi.org/10.1038/s41598-019-49362-z
Mruk, D.D., Silvestrinin, B., Mo, M.Y. and Cheng, C.Y. 2002. Antioxidant superoxide dismutase—a review: its function, regulation in the testis, and role in male fertility. Contraception. 65:305–311. https://doi.org/10.1016/S0010-7824(01)00320-1
Nichole, C., Ying, Z., Marian, N. and Fereidoon, S. 2008. Antioxidant activity and water-holding capacity of canola protein hydrolysates. Food Chem. 109:144–148. https://doi.org/10.1016/j.foodchem.2007.12.039
Ogłuszka, M., Chen, C.Y., Poławska, E., Starzyński, R.R., Liput, K., Siekierko, U., Pareek, C.S., Pierzchała, M. and Kang, J.X. 2024. Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice. Clin Nutr. 43(6):1488–1494. https://doi.org/10.1016/j.clnu.2024.05.001
Pham-Huy, Z.A., He, H. and Pham-Huy, C. 2008. Free radicals and antioxidants in disease and health. Int J Biomed Sci. 4:89–96. https://doi.org/10.59566/IJBS.2008.4089
Pisoschi, A.M. and Negulescu, G.P. 2011. Methods for total antioxidant activity determination: a review. Bioch Analyt Bioch. 1. https://doi.org/10.4172/2161-1009.1000106
Rahim, M.A., Imran, M., Ambreen, S., Khan, F.A., Regenstein, J.M., Al-Asmari, F., Oranab, S., Nadeem, M., Hussain, I., et al. 2023. Stabilization of the Antioxidant Properties in Spray-Dried Microcapsules of Fish and Chia Oil Blends. ACS Omega. 2023 18(38):35183-35192. https://doi.org/10.1021/acsomega.3c04634
Razavi, M., Jamilian, M., Samimi, M., Afshar Ebrahimi, F., Taghizadeh, M., Bekhradi, R., Seyed Hosseini, E., Haddad Kashani, H., Karamali, M. and Asemi Z. 2017. The effects of vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress, and pregnancy outcomes in patients with gestational diabetes. Nutr Metab (Lond). 14:80. https://doi.org/10.1186/s12986-017-0236-9
Saboori, S., Koohdani, F., Nematipour, E., Yousefi Rad, A.A., Saboor-Yaraghi, M.H., Javanbakht, M.R., Eshraghian, A. and Ramezani, M. 2016. Beneficial effects of omega-3 and vitamin E co-administration on gene expression of SIRT1 and PGC1α and serum antioxidant enzymes in patients with coronary artery disease. Nut Metab Cardiovasc Dis. 26(6):489–494. https://doi.org/10.1016/j.numecd.2015.11.013
Saini, R.K. and Keum, Y.S. 2018. Omega-3 and omega-6 polyunsaturated fatty acids: dietary sources, metabolism, and significance—a review. Life Sci. 203:255–267. https://doi.org/10.1016/j.lfs.2018.04.049
Saini, R.K., Prasad, P., Sreedhar, R.V., Akhilender Naidu, K., Shang, X., and Keum, Y.S. 2021. Omega-3 polyunsaturated fatty acids (PUFAs): emerging plant and microbial sources, oxidative stability, bioavailability, and health benefits—a review. Antioxidants (Basel). 10(10):1627. https://doi.org/10.3390/antiox10101627
Sarikaya, M., Aslan, M., Çinar, V., Çibuk, S., Selcuk, M. , Embiyaoglu, N.M. and Öge, B. 2023. Antioxidant effect of omega-3 fatty acids on exercise-induced oxidative stress in rats. Eur Rev Med Pharmacol Sci. 27: 8324–8329.
Sepidarkish, M., Akbari-Fakhrabadi, M., Daneshzad, E., Yavari, M., Rezaeinejad, M., Morvaridzadeh, M. and Heshmati. 2020. Effect of omega-3 fatty acid plus vitamin E co-supplementation on oxidative stress parameters: a systematic review and meta-analysis. J Clin Nutr. 39(4):1019–1025. https://doi.org/10.1016/j.clnu.2019.05.004
Sharma, H., Rawal, N. and Mathew, B.B. 2015. The characteristics, toxicity, and effects of cadmium. Int J Nanotech Nanosci. 3:1–9.
Smith, G.I., Atherton, P., Reeds, D.N., Mohammed, B.S., Rankin, D., et al. 2011. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr. 93(2):402–412. https://doi.org/10.3945/ajcn.110.005611
Soleimani, A., Taghizadeh, M., Bahmani, F., Badroj, N. and Asemi, Z. 2017. Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial. Clin Nut. 36(1):79–84. https://doi.org/10.1016/j.clnu.2015.11.003
Staudacher, V., Trujillo, M., Diederichs, T., Dick, T.P. and Radi, R. 2018. Redox-sensitive GFP fusions for monitoring the catalytic mechanism and inactivation of peroxiredoxins in living cells. Redox Biol. 14:549–556. https://doi.org/10.1016/j.redox.2017.10.017
Tantipaiboonwong, P., Chaiwangyen, W., Suttajit, M., Kangwan, N., Kaowinn, S, Khanaree, C, Punfa, W. and Pintha, K. 2021. Molecular mechanism of antioxidant and anti-inflammatory effects of omega-3 fatty acids in perilla seed oil and rosmarinic acid rich fraction extracted from perilla seed meal on TNF-α induced A549 lung adenocarcinoma cells. Molecules. 26:6757. https://doi.org/10.3390/molecules26226757
Temleton, D.M. and Liu, Y. 2010. Multiple roles of cadmium in cell death and survival. Chemo Biol. Interactions. 188:267–275. https://doi.org/10.1016/j.cbi.2010.03.040
Wang, X., Zhu, H., Chen, B., Zhang, Y., Kok, A., van Knegsel, A., Zhang, S., Pang, X., Jiang, S., Kemp, B., Lu, J. and Lv, J. 2024. Effects of endogenous DHA milk and exogenous DHA milk on oxidative stress and cognition in SAMP8 mice. Biomed Pharmacother. 174:116467. https://doi.org/10.1016/j.biopha.2024.116467
Yong, S., Lulu, W., Ying, W., Xiaqian, O. and Zhaoyuan, S. 2017. Purification and identification of a natural antioxidant protein from fertilized eggs. Korea J Food Sci Anim Resour. 37:764–772. https://doi.org/10.5851/kosfa.2017.37.5.764
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Al-Zharani, M., Rudayni, H., Mubarak, M., Alkahtani, S., Nasr, F., Albatli, S., Alawam, A. S., Al-Doaiss, A., & Al-eissa, M. S. (n.d.). Omega-3 fatty acids (EPA/DHA) act as a natural antioxidant to alleviate cadmium-induced oxidative stress and restore the oxidation/antioxidant balance in male Wistar mice. Italian Journal of Food Science, 38(1). https://doi.org/10.15586/
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Al-Zharani, M., Rudayni, H., Mubarak, M., Alkahtani, S., Nasr, F., Albatli, S., Alawam, A. S., Al-Doaiss, A., & Al-eissa, M. S. (n.d.). Omega-3 fatty acids (EPA/DHA) act as a natural antioxidant to alleviate cadmium-induced oxidative stress and restore the oxidation/antioxidant balance in male Wistar mice. Italian Journal of Food Science, 38(1). https://doi.org/10.15586/