Assessing the impact of oleuropein on dyslipidemia in male rats subjected to D-galactose-induced aging: A preliminary study
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DOI:
https://doi.org/10.62063/ecb-21Keywords:
Aging, dyslipidemia, oleuropein, peroxisome proliferator-activated receptor alphaAbstract
Aging unfolds as a complex process marked by numerous physiological and biochemical transformations. These age-related changes intricately influence tissues, cells, and subcellular organelles, thereby impacting metabolic functions. Dyslipidemia, characterized by elevated triglyceride (TAG) and low-density lipoprotein (LDL-C) levels coupled with diminished high-density lipoprotein (HDL-C) levels, stands as a well-recognized risk factor for cardiovascular disease, which increases with age. The regulation of lipoprotein metabolism relies upon various proteins, notably peroxisome proliferator-activated receptor alpha (PPAR-α). In this study, we sought to elucidate the potential of oleuropein in addressing dyslipidemia associated with aging through a preliminary analysis of liver and plasma samples to assess lipid profiles. Our study included control, D-galactose-treated (aged) (150 mg/kg), and oleuropein (200 mg/kg) pretreated aged groups. The rat plasma levels of TAG, total cholesterol (TC), HDL-C and LDL-C were assessed using their respective kits. Liver tissues were homogenized with PBS at a ratio of 1:9 and PPAR-α levels were assessed using the PPAR-α Elisa kit. D-galactose induced aging resulted in significant increase in plasma TAG, TC, LDL-C (p<0.05) and decrease in plasma HDL-C (p<0.05) and liver PPAR-α (p<0.001) levels. However, oleuropein pretreatment mitigated these affects in the oleuproein+D-galactose group resulting in statistically lower levels of TAG, TC and LDL-C levels (p<0.05) and higher levels of liver PPAR-α (p<0.05) compared to the aged group. Collectively, our study highlights oleuropein's potential as a PPAR agonist in maintaining liver PPAR-α levels, regulating plasma lipid levels, and improving dyslipidemia in aging individuals.
References
Ahamad, J., Toufeeq, I., Khan, M. A., Ameen, M. S. M., Anwer, E. T., Uthirapathy, S., Mir, S. R., & Ahmad, J. (2019). Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome. Phytotherapy research, 33(12), 3112-3128. https://doi.org/10.1002/ptr.6511
Ahmadvand, H., Bagheri, S., Tamjidi-Poor, A., Cheraghi, M., Azadpour, M., Ezatpour, B., Moghadam, S., Shahsavari, G., & Jalalvand, M. (2016). Biochemical effects of oleuropein in gentamicin-induced nephrotoxicity in rats. ARYA Atheroscler, 12(2), 87-93.
Albers, J. J., Warnick, G. R., & Chenng, M. C. (1978). Quantitation of high density lipoproteins. Lipids, 13(12), 926-932. https://doi.org/10.1007/bf02533852
Allain, C. C., Poon, L. S., Chan, C. S., Richmond, W., & Fu, P. C. (1974). Enzymatic determination of total serum cholesterol. Clinical chemistry, 20(4), 470-475. https://doi.org/10.1093/clinchem/20.4.470
Andreadou, I., Iliodromitis, E. K., Mikros, E., Constantinou, M., Agalias, A., Magiatis, P., Skaltsounis, A. L., Kamber, E., Tsantili-Kakoulidou, A., & Kremastinos, D. T. (2006). The olive constituent oleuropein exhibits anti-ischemic, antioxidative, and hypolipidemic effects in anesthetized rabbits. Journal of nutrition, 136(8), 2213-2219. https://doi.org/10.1093/jn/136.8.2213
Bae, S., & Moon, Y. A. (2024). Deletion of Elovl5 leads to dyslipidemia and atherosclerosis in LDLR-deficient mice. Biochemical and biophysical research communications, 690, Article 149292. https://doi.org/10.1016/j.bbrc.2023.149292
Balakumar, P., Arora, M. K., & Singh, M. (2009). Emerging role of PPAR ligands in the management of diabetic nephropathy. Pharmacological research, 60(3), 170-173. https://doi.org/10.1016/j.phrs.2009.01.010
Campolo, M., Di Paola, R., Impellizzeri, D., Crupi, R., Morittu, V. M., Procopio, A., Perri, E., Britti, D., Peli, A., Esposito, E., & Cuzzocrea, S. (2013). Effects of a polyphenol present in olive oil, oleuropein aglycone, in a murine model of intestinal ischemia/reperfusion injury. Journal of leukocyte biology, 93(2), 277-287. https://doi.org/10.1189/jlb.0712317
Chi, T. G., Wang, M. N., Wang, X., Yang, K., Xie, F. Y., Liao, Z. H., & Wei, P. (2021). PPAR-γ Modulators as Current and Potential Cancer Treatments. Frontiers in oncology, 11, Article 737776. https://doi.org/10.3389/fonc.2021.737776
Feng, L., Luo, H., Xu, Z., Yang, Z., Du, G., Zhang, Y., Yu, L., Hu, K., Zhu, W., Tong, Q., Chen, K., Guo, F., Huang, C., & Li, Y. (2016). Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice. Diabetologia, 59(6), 1276-1286. https://doi.org/10.1007/s00125-016-3912-9
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of lowdensity lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry, 18(6), 499-502.
Giansanti, R., Fumelli, C., Boemi, M., & Fumelli, P. (1996). Age-related macular disease in diabetes mellitus. Archives of gerontology and geriatrics, 473-476. https://doi.org/10.1016/0167-4943(96)86985-8
Gu, S. J., Guo, Z. R., Zhou, Z. Y., Hu, X. S., & Wu, M. (2014). PPAR α and PPAR γ Polymorphisms as risk factors for Dyslipidemia in a Chinese han population. Lipids in health and disease, 13, Article 23. https://doi.org/10.1186/1476-511x-13-23
Hakimizadeh, E., Tadayon, S., Zamanian, M. Y., Soltani, A., Giménez-Llort, L., Hassanipour, M., & Fatemi, I. (2023). Gemfibrozil, a lipid-lowering drug, improves hepatorenal damages in a mouse model of aging. Fundamental & clinical pharmacology, 37(3), 599-605. https://doi.org/10.1111/fcp.12865
Hakimizadeh, E., Zamanian, M. Y., Borisov, V. V., Giménez-Llort, L., Ehsani, V., Kaeidi, A., Hassanshahi, J., Khajehasani, F., Movahedinia, S., & Fatemi, I. (2022). Gemfibrozil, a lipid-lowering drug, reduces anxiety, enhances memory, and improves brain oxidative stress in d-galactose-induced aging mice. Fundamental & clinical pharmacology, 36(3), 501-508. https://doi.org/10.1111/fcp.12752
Jensen, V. S., Fledelius, C., Wulff, E. M., Lykkesfeldt, J., & Hvid, H. (2021). Temporal Development of Dyslipidemia and Nonalcoholic Fatty Liver Disease (NAFLD) in Syrian Hamsters Fed a High-Fat, High-Fructose, High-Cholesterol Diet. Nutrients, 13(2), Article 604. https://doi.org/10.3390/nu13020604
Kar, F., Çiftçi, H., Er Çalışkan, Ç., Özkaya, A., & Güçlü, K. (2022). Evaluation of The Effects of Pomegranate Juice on Hepato-Nephrotoxicity in Male Rats Exposed to Aluminum. Kahramanmaraş sütçü imam üniversitesi tarım ve doğa dergisi, 25(2), 215-222. https://doi.org/10.18016/ksutarimdoga.vi.896611
Malliou, F., Andreadou, J., Gonzalez, F. J., Lazou, A., Xepapadaki, E., Vallianou, J., Lambrinidis, G., Mikros, E., Marselos, M., Skaltsounis, A. L., & Konstandi, M. (2018). The olive constituent oleuropein, as a PPARα agonist, markedly reduces serum triglycerides. Journal of nutritional biochemistry, 59, 17-28. https://doi.org/10.1016/j.jnutbio.2018.05.013
McGowan, M. W., Artiss, J. D., Strandbergh, D. R., & Zak, B. (1983). A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clinical chemistry, 29(3), 538-542.
Okopien, B., Buldak, L., & Boldys, A. (2017). Fibrates in the management of atherogenic dyslipidemia. Expert review of cardiovascular therapy, 15(12), 913-921. https://doi.org/10.1080/14779072.2017.1408410
Palombo, V., Scurti, R., Muscari, A., Puddu, G. M., DiIorio, A., Zito, M., & Abate, G. (1997). Blood pressure and intellectual function in elderly subjects. Age and ageing, 26(2), 91-98. https://doi.org/10.1093/ageing/26.2.91
Qadir, A., Liang, S., Wu, Z., Chen, Z., Hu, L., & Qian, A. (2020). Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells. International journal of molecular sciences, 21(1). https://doi.org/10.3390/ijms21010349
Roghani-Shahraki, H., Karimian, M., Valipour, S., Behjati, M., Arefnezhad, R., & Mousavi, A. (2021). Herbal therapy as a promising approach for regulation on lipid profiles: A review of molecular aspects. Journal of cellular physiology, 236(8), 5533-5546. https://doi.org/https://doi.org/10.1002/jcp.30282
Ruan, Q., Liu, F., Gao, Z., Kong, D., Hu, X., Shi, D., Bao, Z., & Yu, Z. (2013). The anti-inflamm-aging and hepatoprotective effects of huperzine A in d-galactose-treated rats. Mechanisms of ageing and development, 134(3), 89-97. https://doi.org/https://doi.org/10.1016/j.mad.2012.12.005
Schwartz, J., Allison, M. A., Ancoli-Israel, S., Hovell, M. F., Patterson, R. E., Natarajan, L., Marshall, S. J., & Grant, I. (2013). Sleep, type 2 diabetes, dyslipidemia, and hypertension in elderly Alzheimer‘s caregivers. Archives of gerontology and geriatrics, 57(1), 70-77. https://doi.org/10.1016/j.archger.2013.02.008
Shao, H., Chen, L. Q., & Xu, J. (2011). Treatment of dyslipidemia in the elderly. Journal of geriatric cardiology, 8(1), 55-64. https://doi.org/10.3724/sp.J.1263.2011.00055
Spiteller, G. (2002). Are changes of the cell membrane structure causally involved in the aging process? In D. Harman (Ed.), Increasing Healthy Life Span: Conventional Measures and Slowing the Innate Aging Process (Vol. 959, pp. 30-44). https://doi.org/10.1111/j.1749-6632.2002.tb02080.x
Svobodova, M., Andreadou, I., Skaltsounis, A. L., Kopecky, J., & Flachs, P. (2014). Oleuropein as an inhibitor of peroxisome proliferator-activated receptor gamma. Genes & nutrition, 9(1), 376. https://doi.org/10.1007/s12263-013-0376-0
Terra, S. G., Francone, O. L., Contant, C. F., Gao, X., Lewin, A. J., & Nguyen, T. T. (2008). Efficacy and safety of a potent and selective peroxisome proliferator activated receptor alpha agonist in subjects with dyslipidemia and type 2 diabetes mellitus. American journal of cardiology, 102(4), 434-439. https://doi.org/10.1016/j.amjcard.2008.03.076
van den Berg, E., Kloppenborg, R. P., Kessels, R. P. C., Kappelle, L. J., & Biessels, G. J. (2009). Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition. Biochimica et biophysica acta-molecular basis of disease, 1792(5), 470-481. https://doi.org/10.1016/j.bbadis.2008.09.004
Zhou, Y., Xu, Q., Dong, Y., Zhu, S., Song, S., & Sun, N. (2017). Supplementation of mussel peptides reduces aging phenotype, lipid deposition and oxidative stress in D-galactose-induce aging mice. Journal of nutrition health & aging, 21(10), 1314-1320. https://doi.org/10.1007/s12603-016-0862-3
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