https://doi.org/10.4081/ejh.2021.3322
The possible alleviating effect of garlic supplement on the neural retina in a rat model of hypercholesterolemia: a histological and immunohistochemical study
Submitted: 4 September 2021
Accepted: 1 December 2021
Published: 16 December 2021
Accepted: 1 December 2021
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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The purpose of this work was to prove that oxidative stress is the main mechanism responsible for retinal neurodegenerative changes, subsequent apoptosis, and inflammatory cytokine release in rats fed with a high cholesterol diet (HCD) and determine the role of garlic in alleviating these changes. Forty rats were equally divided into four groups: control, garlic-treated (positive control), HCD, and HCD + garlic-treated (HCD + G). By the end of the experiment (24 weeks) blood samples were collected for assessment of serum lipid profile, oxidative stress parameters, and plasma levels of IL-6 and TNF-α. Both eyes of the rats were enucleated; one was used for light microscopic examination and the other for electron microscopic examination. There was a significant increase in the levels of serum lipids, oxidative stress parameters, IL-6 and TNF-α, and area of expression of caspase-3 in the HCD group compared to both the control and HCD + G groups. Histological examination revealed degenerative changes in all layers of the neural retina in the HCD group. Garlic administration resulted in a significant improvement in the biochemical, immunohistochemical, and histological characteristics of hypercholesterolemic rats. These findings support the hypotheses that garlic has strong antioxidant, anti-apoptotic, and anti-inflammatory properties. Garlic ameliorates the neurodegenerative changes in the neural retina of hypercholesteremic rats.
Duan Y, Zeng L, Zheng C, Song B, Li F, Kong X, Xu K. Inflammatory links between high fat diets and diseases. Front Immunol 2018;9:2649.
DOI: https://doi.org/10.3389/fimmu.2018.02649
Soliman GA. Dietary cholesterol and the lack of EIVdence in cardiovascular disease. Nutrients 2018;10:780.
DOI: https://doi.org/10.3390/nu10060780
Xu C, Li E, Xu Z, Su Y, Lu M, Qin JG, et al. Growth and stress axis responses to dietary cholesterol in Nile tilapia (Oreochromis niloticus) in brackish water. Front Physiol 2018;9:254.
DOI: https://doi.org/10.3389/fphys.2018.00254
Rao SR, FlieslerSJ. Cholesterol homeostasis in the vertebrate retina: biology and pathobiology. J Lipid Res 2021;62:100057.
Fourgeux C, Martine L, Gambert-Nicot S, Bron A, Garcher C, Bretillon L. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis. OCL 2015;22:D204.
DOI: https://doi.org/10.1051/ocl/2014056
Ramachandra Rao S, Fliesler SJ. Cholesterol homeostasis in the vertebrate retina: biology and pathobiology. J Lipid Res 2021;62:100057.
DOI: https://doi.org/10.1194/jlr.TR120000979
Opoku S, Gan Y, Fu W, Chen D, Addo-Yobo E, Trofimovitch D, et al. Prevalence and risk factors for dyslipidemia among adults in rural and urban China: findings from the China National Stroke Screening and prevention project (CNSSPP). BMC Public Health 2019;19:1500.
DOI: https://doi.org/10.1186/s12889-019-7827-5
Vance JE. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis Model Mech 2012;5:746-55.
DOI: https://doi.org/10.1242/dmm.010124
Yücel I, Akar Y, Yücel G, Ciftçioglu MA, Keleş N, Aslan M. Effect of hypercholesterolemia on inducible nitric oxide synthase expression in a rat model of elevated intraocular pressure. Vision Res 2005;45:1107-14.
DOI: https://doi.org/10.1016/j.visres.2004.11.018
Shang A, Cao SY, Xu XY, Gan RY, Tang GY, Corke H, et al. Bioactive compounds and biological functions of garlic (Allium sativum L.). Foods 2019;8:246.
Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control 2014;7:71-82.
DOI: https://doi.org/10.2147/IBPC.S51434
Aquila G, Marracino L, Martino V, Calabria D, Campo G, Caliceti C, et al. The use of nutraceuticals to counteract atherosclerosis: The role of the notch pathway. Oxid Med Cell Longev 2019;2019:5470470.
DOI: https://doi.org/10.1155/2019/5470470
Kim TM, Kim KH, Jo JH, Park J, Kwon YS, Yang JH. Hepatoprotective effect of a novel lactic acid‐fermented garlic extract functional food product against acute liver injury. Food Sci Nutr 2020;8:1012-9.
DOI: https://doi.org/10.1002/fsn3.1385
Moss JW, Ramji DP. Nutraceutical therapies for atherosclerosis. Nat Rev Cardiol 2016;13:513-32.
DOI: https://doi.org/10.1038/nrcardio.2016.103
Liu J, Ji F, Chen FM, Guo W, Yang ML, Huang SX, et al. Determination of garlic phenolic compounds using supercritical fluid extraction coupled to supercritical fluid chromatography/tandem mass spectrometry. J Pharm Biomed Anal 2018;159:513-23.
DOI: https://doi.org/10.1016/j.jpba.2018.07.020
Kang JS, Kim SO, Kim GY, Hwang HJ, Kim BW, Chang YC, et al. An exploration of the antioxidant effects of garlic saponins in mouse-derived C2C12 myoblasts. Int J Mol Med 2016;37:149-56.
DOI: https://doi.org/10.3892/ijmm.2015.2398
Rabe SZT, Ghazanfari T, Siadat Z, Rastin M, Rabe SZT, Mahmoudi M. Anti-inflammatory effect of garlic 14-kDa protein on LPS-stimulated-J774A.1 macrophages. Immunopharmacol Immunotoxicol 2015;37:158-64.
DOI: https://doi.org/10.3109/08923973.2015.1005229
Leung HH, Yau YF, Leung KS, Lee YY, Oger C, Durand T, et al. Garlic supplementation modified enzymatic Omega‐6 polyunsaturated fatty acid oxidation in mild hypercholesterolemia. Eur J Lipid Sci Technol 2019;121:1900069.
DOI: https://doi.org/10.1002/ejlt.201900069
Jung ES, Park SH, Choi EK, Ryu BH, Park BH, Kim DS, et al. Reduction of blood lipid parameters by a 12-wk supplementation of aged black garlic: a randomized controlled trial. Nutrition 2014;30:1034-9.
DOI: https://doi.org/10.1016/j.nut.2014.02.014
Matsuura H. Saponins in garlic as modifiers of the risk of cardiovascular disease. J Nutr 2001;131:1000S-5S.
DOI: https://doi.org/10.1093/jn/131.3.1000S
Sun YE, Wang W, Qin J. Anti-hyperlipidemia of garlic by reducing the level of total cholesterol and low-density lipoprotein: A meta-analysis. Medicine (Baltimore) 2018;97:e0255.
DOI: https://doi.org/10.1097/MD.0000000000010255
Cleome ViscosaLinn UR. A natural source of pharmaceuticals and pesticides. Int J Green Pharm 2015;9:71.
DOI: https://doi.org/10.4103/0973-8258.155050
Chinellato A, Ragazzi E, Petrelli L, Paro M, Mironov A, Aliev G. Effect of cholesterol‐supplemented diet in heritable hyperlipidemic Yoshida rats: functional and morphological characterization of thoracic aorta. Atherosclerosis 1994;106:51-63.
DOI: https://doi.org/10.1016/0021-9150(94)90082-5
Aliev G, Shi J, Perry G, Friedland RP, Lamanna JC. Decreased constitutive nitric oxide synthase, but increased inducible nitric oxide synthase and endothelin-1 immunoreactivity in aortic endothelial cells of donryu rats on a cholesterol-enriched diet. Anat Rec 2000;260:16-25.
DOI: https://doi.org/10.1002/1097-0185(20000901)260:1<16::AID-AR20>3.0.CO;2-2
Supakul L, Pintana H, Apaijai N, Chattipakorn S, Shinlapawittayatorn K, Chattipakorn N. Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats. Eur J Nutr 2014;53:919-28.
DOI: https://doi.org/10.1007/s00394-013-0595-6
Meng Q, Shi D, Feng J, Su Y, Long Y, He S, et al. Hypercholesterolemia up-regulates the expression of intermedin and its receptor components in the aorta of rats IVa inducing the oxidative stress. Ann Clin Lab Sci 2016;46:234-40.
Ściskalska M, Ołdakowska M, Marek G, Milnerowicz H. Changes in the activity and concentration of superoxide dismutase isoenzymes (Cu/Zn SOD, MnSOD) in the blood of healthy subjects and patients with acute pancreatitis. Antioxidants (Basel) 2020;9:948.
DOI: https://doi.org/10.3390/antiox9100948
Bancroft JD, Layton C. The hematoxylins and eosin. In: K.S. Suvarna, C. Layton, J.D. Bancroft, editors. Bancroft’s theory and practice of histological techniques e-book. London: Elsevier; 2018. pp. 26-138.
DOI: https://doi.org/10.1016/B978-0-7020-6864-5.00010-4
Kamel Ismail ZM, Morcos MA, Eldin Mohammad MD, Gamal Aboulkhair A. Enhancement of neural stem cells after induction of depression in male albino rats (a histological & immunohistochemical study). Int J Stem Cells 2014;7:70-8.
DOI: https://doi.org/10.15283/ijsc.2014.7.2.70
Dykstra MJ, Reuss LE. Staining methods for semi thins and ultra-thins. In: M.J. Dykstra, L.E. Reuss, editors. Biological electron microscopy, theory, techniques and troubleshooting. Kluwer Academic Publishers/Plenum Press; 2003. pp. 175-96.
DOI: https://doi.org/10.1007/978-1-4419-9244-4_7
Arafat EA, Shabaan DA. The possible neuroprotective role of grape seed extract on the histopathological changes of the cerebellar cortex of rats prenatally exposed to valproic acid: animal model of autism. Acta Histochem 2019;121:841-51.
DOI: https://doi.org/10.1016/j.acthis.2019.08.002
Emsley R, Dunn G, White IR. Mediation and moderation of treatment effects in randomised controlled trials of complex interventions. Stat Methods Med Res 2010;19:237-70.
DOI: https://doi.org/10.1177/0962280209105014
Mahmoud R, Aziza A, Marghani B, Eltaysh R. Influence of ginger and garlic supplementation on growth performance, whole body composition and oxidative stress in the muscles of Nile tilapia (O. niloticus). Adv Anim Vet Sci 2019;7:397-404.
DOI: https://doi.org/10.17582/journal.aavs/2019/7.5.397.404
Ohtani M, Nishimura T. Sulfur-containing amino acids in aged garlic extract inhibit inflammation in human gingival epithelial cells by suppressing intercellular adhesion molecule-1 expression and IL-6 secretion. Biomed Rep 2020;12:99-108.
DOI: https://doi.org/10.3892/br.2019.1269
Fernández-Navarro J, Aldea P, de Hoz R, Salazar JJ, Ramírez AI, Rojas B, et al. Neuroprotective effects of low-dose statins in the retinal ultrastructure of hypercholesterolemic rabbits. PLoS One 2016;11:e0154800.
DOI: https://doi.org/10.1371/journal.pone.0154800
Del Rio D, Stewart AJ, Pellegrini NA. Review of recent studies on malondialdehyde and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005;15:316-28.
DOI: https://doi.org/10.1016/j.numecd.2005.05.003
Farnaghi S, Prasadam I, Cai G, Friis T, Du Z, Crawford R, et al. Protective effects of mitochondria-targeted antioxidants and statins on cholesterol-induced osteoarthritis. FASEB J 2017;31:356-67.
DOI: https://doi.org/10.1096/fj.201600600r
Bozin B, Mimica-Dukic N, Samojlik I, Goran A, Igic R. Phenolics as antioxidants in garlic (Allium sativum L., Alliaceae). Food Chem 2008;111:925-9.
DOI: https://doi.org/10.1016/j.foodchem.2008.04.071
Tsoupras A, Lordan R, Zabetakis I. Inflammation, not cholesterol, is a cause of chronic disease. Nutrients 2018;10:604.
DOI: https://doi.org/10.3390/nu10050604
Ramji DP, Davies TS. Cytokines in atherosclerosis: key players in all stages of disease and promising therapeutic targets. Cytokine Growth Factor Rev 2015;26:673-85.
DOI: https://doi.org/10.1016/j.cytogfr.2015.04.003
Famurewa AC, Ejezie AJ, Ugwu-Ejezie CS, Ikekpeazu EJ, Ejezie FE. Antioxidant and anti-inflammatory mechanisms of polyphenols isolated from virgin coconut oil attenuate cadmium-induced oxidative stress-mediated nephrotoxicity and inflammation in rats. J Appl Biomed 2018;16:281-8.
DOI: https://doi.org/10.1016/j.jab.2018.02.003
Zhou H, Qu Z, Mossine VV, Nknolise DL, Li JL, Chen ZZ, et al. Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells. PLoS One 2014;9:e113531.
DOI: https://doi.org/10.1371/journal.pone.0113531
Shang A, Cao SY, Xu XY, Gan RY, Tang GY, Corke H, et al. Bioactive compounds and biological functions of garlic (Allium sativum L.). Foods 2019;8:246-9.
DOI: https://doi.org/10.3390/foods8070246
Jayanthi MK, Dhar M, Jayanthi M. Anti-inflammatory effects of Allium sativum (garlic) in experimental rats. Biomedicine 2011;31:84-9.
Ban N, Lee TJ, Sene A, Dong Z, Santeford A, Lin JB, et al. Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration. J Lipid Res 2018;59:1414-23.
DOI: https://doi.org/10.1194/jlr.M084442
Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev 2017;2017:8416763.
DOI: https://doi.org/10.1155/2017/8416763
Sánchez-Rivera FJ, Ryan J, Soto-Feliciano YM, Clare Beytagh MC, Xuan L, Feldser DM, et al. Mitochondrial apoptotic priming is a key determinant of cell fate upon p53 restoration. Proc Natl Acad Sci USA 2021;118:e2019740118.
DOI: https://doi.org/10.1073/pnas.2019740118
Farag E, Yousry M, Omar A. Histological study on the detrimental influences of white LED light on the retina of adult albino rat and the potential effect of simultaneous nicotine administration with highlighting their possible mechanisms. Egypt J Histol 2017;40:328-44.
DOI: https://doi.org/10.21608/EJH.2017.4659
Hippert C, Graca AB, Barber AC, West EL, Smith AJ, Ali RR, Pearson RA. Müller glia activation in response to inherited retinal degeneration is highly varied and disease specific. PLoS One 2015;10:e0120415.
DOI: https://doi.org/10.1371/journal.pone.0120415
El-Sayyad HI, Ali DA, Hanafy ME. Fish-oil supplementation improves retinal injury induced by diabetes and hypercholesterolemia in male Wistar rats. Egypt J Basic Appl Sci 2020;7:100-15.
DOI: https://doi.org/10.1080/2314808X.2020.1759003
Nian S, Lo ACY, Mi Y, Ren K, Yang D. Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets. Eye Vis (Lond) 2021;8:15.
DOI: https://doi.org/10.1186/s40662-021-00239-1
How to Cite
Arafat, E. A., Youssef, E. M., & Khalaf, H. A. (2021). The possible alleviating effect of garlic supplement on the neural retina in a rat model of hypercholesterolemia: a histological and immunohistochemical study. European Journal of Histochemistry, 65(4). https://doi.org/10.4081/ejh.2021.3322
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