Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Treatments
2.3. Determination of Lutein and C3G
2.4. Light-Induced Damage
2.5. Electroretinography
2.6. Immunohistochemistry
2.7. Western Blot
2.8. Statistical Analysis
3. Results
3.1. Plasma, Choroid and Retinal Levels of Lutein and C3G
3.2. Combined Efficacy of Lutein and C3G on Oxidative Stress
3.3. Combined Efficacy of Lutein and C3G on Inflammatory Response
3.4. Combined Efficacy of Lutein and C3G on Gliosis and Microglial Activation
3.5. Combined Efficacy of Lutein and C3G on Photoreceptor Degeneration
3.6. Combined Efficacy of Lutein and C3G on Retinal Function
3.7. Efficacy of a Pre-Formulated Mixture on Light-Induced Retinal Damage
4. Discussion
4.1. Light-Induced Retinal Damage
4.2. Preventive Efficacy of Antioxidant Compounds
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Bungau, S.; Abdel-Daim, M.M.; Tit, D.M.; Ghanem, E.; Sato, S.; Maruyama-Inoue, M.; Yamane, S.; Kadonosono, K. Health Benefits of Polyphenols and Carotenoids in Age-Related Eye Diseases. Oxid. Med. Cell. Longev. 2019, 2019, 9783429. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Okano, K.; Maeda, T.; Chauhan, V.; Golczak, M.; Maeda, A.; Palczewski, K. Mechanism of all-trans-retinal toxicity with implications for stargardt disease and age-related macular degeneration. J. Biol. Chem. 2012, 287, 5059–5069. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maeda, T.; Maeda, A.; Matosky, M.; Okano, K.; Roos, S.; Tang, J.; Palczewski, K. Evaluation of potential therapies for a mouse model of human age-related macular degeneration caused by delayed all-trans-retinal clearance. Investig. Ophthalmol. Vis. Sci. 2009, 50, 4917–4925. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Y.; Huo, Y.; Zhao, L.; Lu, F.; Wang, O.; Yang, X.; Ji, B.; Zhou, F. Cyanidin-3-glucoside and its phenolic acid metabolites attenuate visible light-induced retinal degeneration in vivo via activation of Nrf2/HO-1 pathway and NF-κB suppression. Mol. Nutr. Food Res. 2016, 60, 1564–1577. [Google Scholar] [CrossRef]
- Salehi, B.; Martorell, M.; Arbiser, J.L.; Sureda, A.; Martins, N.; Maurya, P.K.; Sharifi-Rad, M.; Kumar, P.; Sharifi-Rad, J. Antioxidants: Positive or Negative Actors? Biomolecules 2018, 8, 124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, P.; Chin, E.K.; Almeida, D. Antioxidants for the Treatment of Retinal Disease: Summary of Recent Evidence. Clin. Ophthalmol. 2021, 15, 1621–1628. [Google Scholar] [CrossRef]
- Ikonne, E.U.; Ikpeazu, V.O.; Ugbogu, E.A. The potential health benefits of dietary natural plant products in age related eye diseases. Heliyon 2020, 6, e04408. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Jin, H.L.; Jang, D.S.; Jeong, K.W.; Choung, S.Y. Quercetin-3-O-α-l-arabinopyranoside protects against retinal cell death via blue light-induced damage in human RPE cells and Balb-c mice. Food Funct. 2018, 9, 2171–2183. [Google Scholar] [CrossRef]
- Sahin, K.; Akdemir, F.; Orhan, C.; Tuzcu, M.; Gencoglu, H.; Sahin, N.; Ozercan, I.H.; Ali, S.; Yilmaz, I.; Juturu, V. (3R, 3’R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers. Cutan. Ocul. Toxicol. 2019, 38, 161–168. [Google Scholar] [CrossRef]
- Shang, Y.M.; Wang, G.S.; Sliney, D.H.; Yang, C.H.; Lee, L.L. Light-emitting-diode induced retinal damage and its wavelength dependency in vivo. Int. J. Ophthalmol. 2017, 10, 1912202. [Google Scholar]
- Li, L.H.; Lee, J.C.; Leung, H.H.; Lam, W.C.; Fu, Z.; Lo, A. Lutein Supplementation for Eye Diseases. Nutrients 2020, 12, 1721. [Google Scholar] [CrossRef]
- Liu, J.; Zhou, H.; Song, L.; Yang, Z.; Qiu, M.; Wang, J.; Shi, S. Anthocyanins: Promising Natural Products with Diverse Pharmacological Activities. Molecules 2021, 26, 3807. [Google Scholar] [CrossRef] [PubMed]
- Eisenhauer, B.; Natoli, S.; Liew, G.; Flood, V.M. Lutein and Zeaxanthin-Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection. Nutrients 2017, 9, 120. [Google Scholar] [CrossRef] [PubMed]
- Mares, J. Lutein and Zeaxanthin Isomers in Eye Health and Disease. Annu. Rev. Nutr. 2016, 36, 571–602. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, T.; Liu, W.H.; Zhao, J.S.; Meng, F.Z.; Wang, H. Lutein protects against β-amyloid peptide-induced oxidative stress in cerebrovascular endothelial cells through modulation of Nrf-2 and NF-κb. Cell Biol. Toxicol. 2017, 33, 57–67. [Google Scholar] [CrossRef]
- Chang, J.; Zhang, Y.; Li, Y.; Lu, K.; Shen, Y.; Guo, Y.; Qi, Q.; Wang, M.; Zhang, S. NrF2/ARE and NF-κB pathway regulation may be the mechanism for lutein inhibition of human breast cancer cell. Future Oncol. 2018, 14, 719–726. [Google Scholar] [CrossRef] [PubMed]
- Bernstein, P.S.; Li, B.; Vachali, P.P.; Gorusupudi, A.; Shyam, R.; Henriksen, B.S.; Nolan, J.M. Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease. Prog. Retin. Eye Res. 2016, 50, 34–66. [Google Scholar] [CrossRef] [Green Version]
- Harborne, J.B.; Williams, C.A. Anthocyanins and other flavonoids. Nat. Prod. Rep. 2001, 18, 310–333. [Google Scholar] [CrossRef]
- Bosch-Morell, F.; Villagrasa, V.; Ortega, T.; Acero, N.; Muñoz-Mingarro, D.; González-Rosende, M.E.; Castillo, E.; Sanahuja, M.A.; Soriano, P.; Martínez-Solís, I. Medicinal plants and natural products as neuroprotective agents in age-related macular degeneration. Neural Regen Res. 2020, 15, 2207–2216. [Google Scholar]
- Pawlowska, E.; Szczepanska, J.; Koskela, A.; Kaarniranta, K.; Blasiak, J. Dietary Polyphenols in Age-Related Macular Degeneration: Protection against Oxidative Stress and Beyond. Oxid. Med. Cell. Longev. 2019, 2019, 9682318. [Google Scholar] [CrossRef]
- Leena, M.M.; Silvia, M.G.; Vinitha, K.; Moses, J.A.; Anandharamakrishnan, C. Synergistic potential of nutraceuticals: Mechanisms and prospects for futuristic medicine. Food Funct. 2020, 11, 9317–9337. [Google Scholar] [CrossRef] [PubMed]
- Sanz, M.M.; Johnson, L.E.; Ahuja, S.; Ekström, P.A.; Romero, J.; van Veen, T. Significant photoreceptor rescue by treatment with a combination of antioxidants in an animal model for retinal degeneration. Neuroscience 2007, 145, 1120–1129. [Google Scholar] [CrossRef] [PubMed]
- Kohno, H.; Chen, Y.; Kevany, B.M.; Pearlman, E.; Miyagi, M.; Maeda, T.; Palczewski, K.; Maeda, A. Photoreceptor proteins initiate microglial activation via Toll-like receptor 4 in retinal degeneration mediated by all-trans-retinal. J. Biol. Chem. 2013, 288, 15326–15341. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rashid, K.; Wolf, A.; Langmann, T. Microglia Activation and Immunomodulatory Therapies for Retinal Degenerations. Front. Cell. Neurosci. 2018, 12, 176. [Google Scholar] [CrossRef]
- Nair, A.B.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 2016, 7, 27–31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Riccitelli, S.; Di Paolo, M.; Ashley, J.; Bisti, S.; Di Marco, S. The Time courses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague-Dawley Rat Retinas. Cells 2021, 10, 1561. [Google Scholar] [CrossRef]
- Ma, H.; Qin, S.; Zhao, S. Osteoarthritis is Prevented in Rats by Verbascoside via Nuclear Factor kappa B (NF-kB) Pathway Downregulation. Med. Sci. Monit. 2020, 26, e921276. [Google Scholar] [CrossRef]
- Xu, G.; Guo, J.; Sun, C. Eucalyptol ameliorates early brain injury after subarachnoid haemorrhage via antioxidant and anti-inflammatory effects in a rat model. Pharm. Biol. 2021, 59, 114–120. [Google Scholar] [CrossRef]
- Wenzel, A.; Grimm, C.; Samardzija, M.; Remé, C.E. Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog. Retin. Eye Res. 2005, 24, 275–306. [Google Scholar] [CrossRef]
- Marmoy, O.R.; Viswanathan, S. Clinical electrophysiology of the optic nerve and retinal ganglion cells. Eye Lond. 2021. [Google Scholar] [CrossRef]
- Yang, J.; Li, D.; Zhang, Y.; Zhang, L.; Liao, Z.; Aihemaitijiang, S.; Hou, Y.; Zhan, Z.; Xie, K.; Zhang, Z. Lutein protected the retina from light induced retinal damage by inhibiting increasing oxidative stress and inflammation. J. Funct. Foods 2020, 73, 104107. [Google Scholar] [CrossRef]
- Braakhuis, A.; Raman, R.; Vaghefi, E. The Association between Dietary Intake of Antioxidants and Ocular Disease. Diseases 2017, 5, 3. [Google Scholar] [CrossRef] [Green Version]
- AREDS2 Research Group; Chew, E.Y.; Clemons, T.; SanGiovanni, J.P.; Danis, R.; Domalpally, A.; McBee, W.; Sperduto, R.; Ferris, F.L. The Age-Related Eye Disease Study 2 (AREDS2): Study design and baseline characteristics (AREDS2 report number 1). Ophthalmology 2012, 119, 2282–2289. [Google Scholar]
- Piermarocchi, S.; Saviano, S.; Parisi, V.; Tedeschi, M.; Panozzo, G.; Scarpa, G.; Boschi, G.; Lo Giudice, G. Carmis Study Group Carotenoids in Age-related Maculopathy Italian Study (CARMIS): Two-year results of a randomized study. Eur. J. Ophthalmol. 2012, 22, 216–225. [Google Scholar] [PubMed]
- Hunter, J.J.; Morgan, J.I.; Merigan, W.H.; Sliney, D.H.; Sparrow, J.R.; Williams, D.R. The susceptibility of the retina to photochemical damage from visible light. Prog. Retin. Eye Res. 2012, 31, 28–42. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ouyang, X.; Yang, J.; Hong, Z.; Wu, Y.; Xie, Y.; Wang, G. Mechanisms of blue light-induced eye hazard and protective measures: A review. Biomed. Pharm. 2020, 130, 110577. [Google Scholar] [CrossRef] [PubMed]
- Okamoto, T.; Kawashima, H.; Osada, H.; Toda, E.; Homma, K.; Nagai, N.; Imai, Y.; Tsubota, K.; Ozawa, Y. Dietary Spirulina Supplementation Protects Visual Function From Photostress by Suppressing Retinal Neurodegeneration in Mice. Transl. Vis. Sci. Technol. 2019, 8, 20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tanito, M.; Agbaga, M.P.; Anderson, R.E. Upregulation of thioredoxin system via Nrf2-antioxidant responsive element pathway in adaptive-retinal neuroprotection in vivo and in vitro. Free Radic. Biol. Med. 2007, 42, 1838–1850. [Google Scholar] [CrossRef]
- Domènech, E.B.; Marfany, G. The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies. Antioxidants 2020, 9, 347. [Google Scholar] [CrossRef] [Green Version]
- Arunkumar, R.; Gorusupudi, A.; Bernstein, P.S. The macular carotenoids: A biochemical overview. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2020, 1865, 158617. [Google Scholar] [CrossRef]
- Tena, N.; Martín, J.; Asuero, A.G. State of the Art of Anthocyanins: Antioxidant Activity, Sources, Bioavailability, and Therapeutic Effect in Human Health. Antioxidants 2020, 9, 451. [Google Scholar] [CrossRef] [PubMed]
- Matsumoto, H.; Nakamura, Y.; Iida, H.; Ito, K.; Ohguro, H. Comparative assessment of distribution of blackcurrant anthocyanins in rabbit and rat ocular tissues. Exp. Eye Res. 2006, 83, 348–356. [Google Scholar] [CrossRef] [PubMed]
- Sato, Y.; Kobayashi, M.; Itagaki, S.; Hirano, T.; Noda, T.; Mizuno, S.; Sugawara, M.; Iseki, K. Pharmacokinetic properties of lutein emulsion after oral administration to rats and effect of food intake on plasma concentration of lutein. Biopharm. Drug Dispos. 2011, 32, 151–158. [Google Scholar] [CrossRef] [PubMed]
- Khoo, H.E.; Ng, H.S.; Yap, W.S.; Goh, H.; Yim, H.S. Nutrients for Prevention of Macular Degeneration and Eye-Related Diseases. Antioxidants 2019, 8, 85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nomi, Y.; Iwasaki-Kurashige, K.; Matsumoto, H. Therapeutic Effects of Anthocyanins for Vision and Eye Health. Molecules 2019, 24, 3311. [Google Scholar] [CrossRef] [Green Version]
- Vitaglione, P.; Donnarumma, G.; Napolitano, A.; Galvano, F.; Gallo, A.; Scalfi, L.; Fogliano, V. Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J. Nutr. 2007, 137, 2043–2048. [Google Scholar] [CrossRef] [PubMed]
- Kamoshita, M.; Toda, E.; Osada, H.; Narimatsu, T.; Kobayashi, S.; Tsubota, K.; Ozawa, Y. Lutein acts via multiple antioxidant pathways in the photo-stressed retina. Sci. Rep. 2016, 6, 30226. [Google Scholar] [CrossRef]
- Sukprasansap, M.; Chanvorachote, P.; Tencomnao, T. Cyanidin-3-glucoside activates Nrf2-antioxidant response element and protects against glutamate-induced oxidative and endoplasmic reticulum stress in HT22 hippocampal neuronal cells. BMC Complement. Med. Ther. 2020, 20, 46. [Google Scholar] [CrossRef] [Green Version]
- Sasaki, M.; Yuki, K.; Kurihara, T.; Miyake, S.; Noda, K.; Kobayashi, S.; Ishida, S.; Tsubota, K.; Ozawa, Y. Biological role of lutein in the light-induced retinal degeneration. J. Nutr. Biochem. 2012, 23, 423–429. [Google Scholar] [CrossRef]
- Randazzo, J.; Zhang, Z.; Hoff, M.; Kawada, H.; Sachs, A.; Yuan, Y.; Haider, N.; Kador, P. Orally active multi-functional antioxidants are neuroprotective in a rat model of light-induced retinal damage. PLoS ONE 2011, 6, e21926. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Prieto, M.A.; Curran, T.P.; Gowen, A.; Vázquez, J.A. An efficient methodology for quantification of synergy and antagonism in single electron transfer antioxidant assays. Food Res. Int. 2015, 67, 284–298. [Google Scholar] [CrossRef] [Green Version]
- Olszowy, M.; Dawidowicz, A.L.; Jóźwik-Dolęba, M. Are mutual interactions between antioxidants the only factors responsible for antagonistic antioxidant effect of their mixtures? Additive and antagonistic antioxidant effects in mixtures of gallic, ferulic and caffeic acids. Eur. Food Res. Technol. 2019, 245, 1473–1485. [Google Scholar] [CrossRef] [Green Version]
- Olivares-González, L.; Velasco, S.; Campillo, I.; Salom, D.; González-García, E.; Soriano Del Castillo, J.M.; Rodrigo, R. Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice. Antioxidants 2021, 10, 1033. [Google Scholar] [CrossRef] [PubMed]
- Dong, C.J.; Hare, W.A. Contribution to the kinetics and amplitude of the electroretinogram b-wave by third-order retinal neurons in the rabbit retina. Vis. Res. 2000, 40, 579–589. [Google Scholar] [CrossRef] [Green Version]
- Kamińska, A.; Romano, G.L.; Rejdak, R.; Zweifel, S.; Fiedorowicz, M.; Rejdak, M.; Bajka, A.; Amato, R.; Bucolo, C.; Avitabile, T.; et al. Influence of Trace Elements on Neurodegenerative Diseases of The Eye-The Glaucoma Model. Int. J. Mol. Sci. 2021, 22, 4323. [Google Scholar] [CrossRef] [PubMed]
- Blasiak, J.; Pawlowska, E.; Chojnacki, J.; Szczepanska, J.; Chojnacki, C.; Kaarniranta, K. Zinc and Autophagy in Age-Related Macular Degeneration. Int. J. Mol. Sci. 2020, 21, 4994. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Georgiev, M.I.; Cao, H.; Nahar, L.; El-Seedi, H.R.; Sarker, S.D.; Xiao, J.; Lu, B. Therapeutic potential of phenylethanoid glycosides: A systematic review. Med. Res. Rev. 2020, 40, 2605–2649. [Google Scholar] [CrossRef]
- Chen, Q.; Xi, X.; Zeng, Y.; He, Z.; Zhao, J.; Li, Y. Acteoside inhibits autophagic apoptosis of retinal ganglion cells to rescue glaucoma-induced optic atrophy. J. Cell. Biochem. 2019, 120, 13133–13140. [Google Scholar] [CrossRef] [Green Version]
- Mosca, M.; Ambrosone, L.; Semeraro, F.; Casamassima, D.; Vizzarri, F.; Costagliola, C. Ocular tissues and fluids oxidative stress in hares fed on verbascoside supplement. Int. J. Food Sci. Nutr. 2014, 65, 235–240. [Google Scholar] [CrossRef] [PubMed]
Antibody | Dilution | Source | Catalogue |
---|---|---|---|
Rabbit monoclonal anti-Bax | 1:500 | Abcam | ab182733 |
Rabbit polyclonal anti-Bcl-2 | 1:500 | Abcam | ab194583 |
Rabbit polyclonal anti-cleaved caspase 3 | 1:500 | Abcam | ab2302 |
Rabbit monoclonal anti-Nrf2 | 1:300 | Abcam | ab62352 |
Rabbit polyclonal anti-HO-1 | 1:500 | Abcam | ab13243 |
Rabbit polyclonal anti-pNF-kB p65 (Ser 536) | 1:100 | Santa Cruz Biotechnology | sc-33020 |
Rabbit polyclonal anti-NF-kB p65 | 1:1000 | Abcam | ab16502 |
Mouse monoclonal anti-IL-6 | 1:100 | Santa Cruz Biotechnology | sc-57315 |
Goat polyclonal anti-IL-10 | 1:100 | Santa Cruz Biotechnology | sc-1783 |
Mouse monoclonal anti-β-actin | 1:2500 | Sigma-Aldrich | A2228 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Amato, R.; Canovai, A.; Melecchi, A.; Pezzino, S.; Corsaro, R.; Dal Monte, M.; Rusciano, D.; Bagnoli, P.; Cammalleri, M. Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model. Biomedicines 2021, 9, 1177. https://doi.org/10.3390/biomedicines9091177
Amato R, Canovai A, Melecchi A, Pezzino S, Corsaro R, Dal Monte M, Rusciano D, Bagnoli P, Cammalleri M. Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model. Biomedicines. 2021; 9(9):1177. https://doi.org/10.3390/biomedicines9091177
Chicago/Turabian StyleAmato, Rosario, Alessio Canovai, Alberto Melecchi, Salvatore Pezzino, Roberta Corsaro, Massimo Dal Monte, Dario Rusciano, Paola Bagnoli, and Maurizio Cammalleri. 2021. "Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model" Biomedicines 9, no. 9: 1177. https://doi.org/10.3390/biomedicines9091177