Impact of aging on kidneys of male Wistar albino rats: the protective antiaging role of resveratrol
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Abstract
Because aging leads to multiple health problems associated with changes in the structure and functions of a different organ system, this study aimed to assess the effect of aging on the histology of renal tissue in rats of various ages and the possible protective role of resveratrol. In the present study, twenty-four male Wistar albino rats were separated into three groups of eight animals each, including rats adult aged (6 months), and old-aged (24 months old). The elderly resveratrol-treated group was administered 25 mg/kg/day of resveratrol diluted in distilled water orally via gastric tube. The treatment lasted three months. At the end of the experiment, blood was drawn for serum creatinine analysis, the animals were sacrificed, and the kidneys were removed and processed for histological investigation. The findings revealed variable changes in kidney tissue, including glomerulosclerosis, compensatory glomerular hypertrophy, tubulointerstitial fibrosis, thickened glomerular basement membrane, arterial sclerosis, tubular dilatation with cast formation, atrophy of the tubules, infiltration of inflammatory cells, a rise in the rate of apoptotic cells, and a decrease in the glomerular number. These histological changes were associated with increased serum creatinine levels and kidney malondialdehyde (MDA), a marker of lipid peroxidation. The use of RES (Resveratrol) improved the creatinine level with a decrease in the MDA and improved the histological changes of aged kidney. As a result, the progression of aging was accompanied by different histological variations that interfered with the physiological functioning of the kidney, predisposing older persons to renal illnesses. Utilizing RES as a prophylactic and/or therapeutic medicine for aging-related renal changes is also possible.
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Keywords
Ageing, Albino rates, Apoptosis, Glomerulosclerosis, Kidney, Resveratrol
References
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Abdulqader, S. W., Faisal, I. M., Saeed, M. G., & Merkhan, M. M. (2022). Fluvoxamine suppressed oxidative stress associated with tissue erosion. Research Journal of Pharmacy and Technology, 15(2), 819-824.doi:10.52711/0974-360X.2022.00136.
Abrass, C. K., Adcox, M. J., & Raugi, G. J. (1995). Aging-associated changes in renal extracellular matrix. The American journal of pathology, 146(3), 742.
Al-Hussaini, H., & Kilarkaje, N. (2018). Trans-resveratrol mitigates type 1 diabetes-induced oxidative DNA damage and accumulation of advanced glycation end products in glomeruli and tubules of rat kidneys. Toxicology and applied pharmacology, 339, 97-109.doi:10.1016/j.taap.201 7.11.025.
Costello-White, R., Ryff, C. D., & Coe, C. L. (2015). Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA. Age, 37, 1-10.doi:10.1007/s11357-015-9808-7
Denic, A., Glassock, R. J., & Rule, A. D. (2016). Structural and functional changes with the aging kidney. Advances in chronic kidney disease, 23(1), 19-28. doi:10.1053/j.ackd.2015.08.004.
Al Dera, H. S. (2016). Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats. Saudi medical journal, 37(4), 369. doi:10.15537/smj.2016.4.13611.
Elbe, H., Vardi, N. İ. G. A. R., Esrefoglu, M. U. K. A. D. D. E. S., Ates, B., Yologlu, S., & Taskapan, C. (2015). Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Human & experimental toxicology, 34(1), 100-113. doi:10.1177/09 60327114531995.
Fang, Y., Gong, A. Y., Haller, S. T., Dworkin, L. D., Liu, Z., & Gong, R. (2020). The ageing kidney: Molecular mechanisms and clinical implications. Ageing research reviews, 63, 101151. doi:10.1016/j.arr.2020.101151.
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., & Salvioli, S. (2007). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mechanisms of ageing and development, 128(1), 92-105. doi:10.1016/j.mad.2006.11.016.
Ginés, C., Cuesta, S., Kireev, R., García, C., Rancan, L., Paredes, S. D., ... & Tresguerres, J. A. (2017). Protective effect of resveratrol against inflammation, oxidative stress and apoptosis in pancreas of aged SAMP8 mice. Experimental Gerontology, 90, 61-70.doi:10.1016/j.exger.2017.01.021.
Glassock, R. J., & Rule, A. D. (2012). The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney international, 82(3), 270-277. doi:10.1038/ki.2012.65.
Harikumar, K. B., & Aggarwal, B. B. (2008). Resveratrol: a multitargeted agent for age-associated chronic diseases. Cell cycle, 7(8), 1020-1035. doi:10.4161/cc.7.8.5740.
Harkema, L., Youssef, S. A., & de Bruin, A. (2016). Pathology of mouse models of accelerated aging. Veterinary pathology, 53(2), 366-389. doi:10.1177/03009858 156251 69.
Hegazy, R. (2015). Hegazy’simplified method of tissue processing (consuming time and chemicals). Ann. Int. Med. Dent. Res, 1(2), 57-61.
James, M. T., Hemmelgarn, B. R., Wiebe, N., Pannu, N., Manns, B. J., Klarenbach, S. W., & Tonelli, M. (2010). Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. The Lancet, 376(9758), 2096-2103. doi:10.1016/S0140-6736(10)61271-8.
Karakaya, F. B., & Eşrefoğlu, M. (2022). Aging-related changes in rat kidney and testis: A microscopic approach. doi:10.26717/BJSTR.2022.47.007445.
Kim, E. N., Lim, J. H., Kim, M. Y., Ban, T. H., Jang, I. A., Yoon, H. E., & Choi, B. S. (2018). Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury. Aging (Albany NY), 10(1), 83. doi:10.18632/agibg.101361.
Kirkwood, T. B. (2005). Understanding the odd science of aging. Cell, 120(4), 437-447. doi:10.1016/j.cell.200 5.01.027.
Kotob, M. H. A., Hussein, A., & Abd-Elkareem, M. (2021). Histopathological changes of kidney tissue during aging. SVU-International Journal of Veterinary Sciences, 4(1), 54-65. doi:10.21608/svu.2021.55868.1092.
Meng, X., Zhou, J., Zhao, C. N., Gan, R. Y., & Li, H. B. (2020). Health benefits and molecular mechanisms of resveratrol: A narrative review. Foods, 9(3), 340. doi:10.33 90/foods9030340.
Nankivell, B. J. (2001). Creatinine clearance and the assessment of renal function. Australian Prescriber, 24(1), 15. doi:10.18773/austprescr.2001.009.
Nitta, K., Okada, K., Yanai, M., & Takahashi, S. (2014). Aging and chronic kidney disease. Kidney and Blood Pressure Research, 38(1), 109-120. doi:10.1159/00 0355760.
Oscanoa, T. J., Amado, J. P., Romero-Ortuno, R., & Hidalgo, J. A. (2018). Estimation of the glomerular filtration rate in older individuals with serum creatinine-based equations: A systematic comparison between CKD-EPI and BIS1. Archives of Gerontology and Geriatrics, 75, 139-145. doi:10.1016/j.archger.2017.12.007.
Pascual, J., Orofino, L., Liano, F., Marcen, R., Naya, M. T., Orte, L., & Ortuno, J. (1990). Incidence and prognosis of acute renal failure in older patients. Journal of the American Geriatrics Society, 38(1), 25-30. doi:10.1111/j.1532-5415.1990.tb01592.x.
Qiao, Y., Gao, K., Wang, Y., Wang, X., & Cui, B. O. (2017). Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway. Experimental and therapeutic medicine, 13(6), 3223-3230. doi:10.3892/etm.2017.4420.
Sarkar, D., & Fisher, P. B. (2006). Molecular mechanisms of aging-associated inflammation. Cancer letters, 236(1), 13-23. doi:10.1016/j.canlet.2005.04.009.
Schmitt, R., & Melk, A. (2017). Molecular mechanisms of renal aging. Kidney international, 92(3), 569-579. doi:10.1016/j.kint.2017.02.036.
Szkudelska, K., Okulicz, M., Hertig, I., & Szkudelski, T. (2020). Resveratrol ameliorates inflammatory and oxidative stress in type 2 diabetic Goto-Kakizaki rats. Biomedicine & Pharmacotherapy, 125, 110026. doi:10.1016/j.biopha.2020.110026.
Tiao JY, Semmens JB, Masarei JR, Lawrence-Brown MM.(2002) The effect of age on serum creatinine levels in an aging population: relevance to vascular surgery. Cardiovascular Surgery,10(5),445-51.doi: 10.1016/s0967-2109(02)00056-x.
Tonelli, M., & Riella, M. C. (2014). World Kidney Day 2014: CKD and the aging population. American Journal of Kidney Diseases, 63(3), 349-353. doi:10.1053/j.ajkd.2014.01.003.
Uddin, M. J., Farjana, M., Moni, A., Hossain, K. S., Hannan, M. A., & Ha, H. (2021). Prospective pharmacological potential of resveratrol in delaying kidney aging. International Journal of Molecular Sciences, 22(15), 8258. doi:10.3390/ijms22158258.
Viña, J., Borrás, C., & Miquel, J. (2007). Theories of ageing. IUBMB life, 59(4‐5), 249-254. doi:10.1080/1521654 0601178067.
Wang, N., Luo, Z., Jin, M., Sheng, W., Wang, H. T., Long, X., & Zhang, X. (2019). Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina. Aging (Albany NY), 11(10), 3117. doi: 10.18632/aging.101966
Wang, X., Bonventre, J. V., & Parrish, A. R. (2014). The aging kidney: increased susceptibility to nephrotoxicity. International journal of molecular sciences, 15(9), 15358-15376.doi:10.3390/ijms150915358.
Zhou, X. J., Rakheja, D., Yu, X., Saxena, R., Vaziri, N. D., & Silva, F. G. (2008). The aging kidney. Kidney international, 74(6), 710-720. doi:10.1038/ki.2008.319.
Abdulqader, S. W., Faisal, I. M., Saeed, M. G., & Merkhan, M. M. (2022). Fluvoxamine provide a gastro-protection against vitiated insult. Indian Journal of Forensic Medicine & Toxicology, 16(1), 1046-1052. doi:10.37506/ijfmt.v16i1.17633.
Abdulqader, S. W., Faisal, I. M., Saeed, M. G., & Merkhan, M. M. (2022). Fluvoxamine suppressed oxidative stress associated with tissue erosion. Research Journal of Pharmacy and Technology, 15(2), 819-824.doi:10.52711/0974-360X.2022.00136.
Abrass, C. K., Adcox, M. J., & Raugi, G. J. (1995). Aging-associated changes in renal extracellular matrix. The American journal of pathology, 146(3), 742.
Al-Hussaini, H., & Kilarkaje, N. (2018). Trans-resveratrol mitigates type 1 diabetes-induced oxidative DNA damage and accumulation of advanced glycation end products in glomeruli and tubules of rat kidneys. Toxicology and applied pharmacology, 339, 97-109.doi:10.1016/j.taap.201 7.11.025.
Costello-White, R., Ryff, C. D., & Coe, C. L. (2015). Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA. Age, 37, 1-10.doi:10.1007/s11357-015-9808-7
Denic, A., Glassock, R. J., & Rule, A. D. (2016). Structural and functional changes with the aging kidney. Advances in chronic kidney disease, 23(1), 19-28. doi:10.1053/j.ackd.2015.08.004.
Al Dera, H. S. (2016). Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats. Saudi medical journal, 37(4), 369. doi:10.15537/smj.2016.4.13611.
Elbe, H., Vardi, N. İ. G. A. R., Esrefoglu, M. U. K. A. D. D. E. S., Ates, B., Yologlu, S., & Taskapan, C. (2015). Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Human & experimental toxicology, 34(1), 100-113. doi:10.1177/09 60327114531995.
Fang, Y., Gong, A. Y., Haller, S. T., Dworkin, L. D., Liu, Z., & Gong, R. (2020). The ageing kidney: Molecular mechanisms and clinical implications. Ageing research reviews, 63, 101151. doi:10.1016/j.arr.2020.101151.
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., & Salvioli, S. (2007). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mechanisms of ageing and development, 128(1), 92-105. doi:10.1016/j.mad.2006.11.016.
Ginés, C., Cuesta, S., Kireev, R., García, C., Rancan, L., Paredes, S. D., ... & Tresguerres, J. A. (2017). Protective effect of resveratrol against inflammation, oxidative stress and apoptosis in pancreas of aged SAMP8 mice. Experimental Gerontology, 90, 61-70.doi:10.1016/j.exger.2017.01.021.
Glassock, R. J., & Rule, A. D. (2012). The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney international, 82(3), 270-277. doi:10.1038/ki.2012.65.
Harikumar, K. B., & Aggarwal, B. B. (2008). Resveratrol: a multitargeted agent for age-associated chronic diseases. Cell cycle, 7(8), 1020-1035. doi:10.4161/cc.7.8.5740.
Harkema, L., Youssef, S. A., & de Bruin, A. (2016). Pathology of mouse models of accelerated aging. Veterinary pathology, 53(2), 366-389. doi:10.1177/03009858 156251 69.
Hegazy, R. (2015). Hegazy’simplified method of tissue processing (consuming time and chemicals). Ann. Int. Med. Dent. Res, 1(2), 57-61.
James, M. T., Hemmelgarn, B. R., Wiebe, N., Pannu, N., Manns, B. J., Klarenbach, S. W., & Tonelli, M. (2010). Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. The Lancet, 376(9758), 2096-2103. doi:10.1016/S0140-6736(10)61271-8.
Karakaya, F. B., & Eşrefoğlu, M. (2022). Aging-related changes in rat kidney and testis: A microscopic approach. doi:10.26717/BJSTR.2022.47.007445.
Kim, E. N., Lim, J. H., Kim, M. Y., Ban, T. H., Jang, I. A., Yoon, H. E., & Choi, B. S. (2018). Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury. Aging (Albany NY), 10(1), 83. doi:10.18632/agibg.101361.
Kirkwood, T. B. (2005). Understanding the odd science of aging. Cell, 120(4), 437-447. doi:10.1016/j.cell.200 5.01.027.
Kotob, M. H. A., Hussein, A., & Abd-Elkareem, M. (2021). Histopathological changes of kidney tissue during aging. SVU-International Journal of Veterinary Sciences, 4(1), 54-65. doi:10.21608/svu.2021.55868.1092.
Meng, X., Zhou, J., Zhao, C. N., Gan, R. Y., & Li, H. B. (2020). Health benefits and molecular mechanisms of resveratrol: A narrative review. Foods, 9(3), 340. doi:10.33 90/foods9030340.
Nankivell, B. J. (2001). Creatinine clearance and the assessment of renal function. Australian Prescriber, 24(1), 15. doi:10.18773/austprescr.2001.009.
Nitta, K., Okada, K., Yanai, M., & Takahashi, S. (2014). Aging and chronic kidney disease. Kidney and Blood Pressure Research, 38(1), 109-120. doi:10.1159/00 0355760.
Oscanoa, T. J., Amado, J. P., Romero-Ortuno, R., & Hidalgo, J. A. (2018). Estimation of the glomerular filtration rate in older individuals with serum creatinine-based equations: A systematic comparison between CKD-EPI and BIS1. Archives of Gerontology and Geriatrics, 75, 139-145. doi:10.1016/j.archger.2017.12.007.
Pascual, J., Orofino, L., Liano, F., Marcen, R., Naya, M. T., Orte, L., & Ortuno, J. (1990). Incidence and prognosis of acute renal failure in older patients. Journal of the American Geriatrics Society, 38(1), 25-30. doi:10.1111/j.1532-5415.1990.tb01592.x.
Qiao, Y., Gao, K., Wang, Y., Wang, X., & Cui, B. O. (2017). Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway. Experimental and therapeutic medicine, 13(6), 3223-3230. doi:10.3892/etm.2017.4420.
Sarkar, D., & Fisher, P. B. (2006). Molecular mechanisms of aging-associated inflammation. Cancer letters, 236(1), 13-23. doi:10.1016/j.canlet.2005.04.009.
Schmitt, R., & Melk, A. (2017). Molecular mechanisms of renal aging. Kidney international, 92(3), 569-579. doi:10.1016/j.kint.2017.02.036.
Szkudelska, K., Okulicz, M., Hertig, I., & Szkudelski, T. (2020). Resveratrol ameliorates inflammatory and oxidative stress in type 2 diabetic Goto-Kakizaki rats. Biomedicine & Pharmacotherapy, 125, 110026. doi:10.1016/j.biopha.2020.110026.
Tiao JY, Semmens JB, Masarei JR, Lawrence-Brown MM.(2002) The effect of age on serum creatinine levels in an aging population: relevance to vascular surgery. Cardiovascular Surgery,10(5),445-51.doi: 10.1016/s0967-2109(02)00056-x.
Tonelli, M., & Riella, M. C. (2014). World Kidney Day 2014: CKD and the aging population. American Journal of Kidney Diseases, 63(3), 349-353. doi:10.1053/j.ajkd.2014.01.003.
Uddin, M. J., Farjana, M., Moni, A., Hossain, K. S., Hannan, M. A., & Ha, H. (2021). Prospective pharmacological potential of resveratrol in delaying kidney aging. International Journal of Molecular Sciences, 22(15), 8258. doi:10.3390/ijms22158258.
Viña, J., Borrás, C., & Miquel, J. (2007). Theories of ageing. IUBMB life, 59(4‐5), 249-254. doi:10.1080/1521654 0601178067.
Wang, N., Luo, Z., Jin, M., Sheng, W., Wang, H. T., Long, X., & Zhang, X. (2019). Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina. Aging (Albany NY), 11(10), 3117. doi: 10.18632/aging.101966
Wang, X., Bonventre, J. V., & Parrish, A. R. (2014). The aging kidney: increased susceptibility to nephrotoxicity. International journal of molecular sciences, 15(9), 15358-15376.doi:10.3390/ijms150915358.
Zhou, X. J., Rakheja, D., Yu, X., Saxena, R., Vaziri, N. D., & Silva, F. G. (2008). The aging kidney. Kidney international, 74(6), 710-720. doi:10.1038/ki.2008.319.
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Impact of aging on kidneys of male Wistar albino rats: the protective antiaging role of resveratrol. (2023). Journal of Applied and Natural Science, 15(3), 926-936. https://doi.org/10.31018/jans.v15i3.4663
