The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ARC | age-related cataracts |
SOD | superoxide dismutase |
AGEs | advanced glycation end products |
DM | diabetes mellitus |
CML | carboxymethyl-lysine |
TH | total hydroperoxides |
ROS | reactive oxygen species |
RAGE | receptor of AGEs |
References
- Vision Loss Expert Group of the Global Burden of Disease Study. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study. Lancet Glob. Health 2021, 9, e144–e160. [Google Scholar] [CrossRef] [PubMed]
- Ministry of Health, Labour and Welfare. Overview of National Medical Expenditures 2021. Available online: www.mhlw.go.jp› toukei› saikin› k-iryohi› data (accessed on 30 June 2024).
- Obara, Y. The oxidative stress in the cataract formation. Nippon. Ganka Gakkai Zasshi 1995, 99, 1303–1341. [Google Scholar] [PubMed]
- Lin, J. Pathophysiology of cataracts: Copper ion and peroxidation in diabetics. Jpn. J. Ophthalmol. 1997, 41, 130–137. [Google Scholar] [CrossRef] [PubMed]
- Truscott, R.J. Age-related nuclear cataract-oxidation is the key. Exp. Eye Res. 2005, 80, 701–725. [Google Scholar] [CrossRef]
- Ma, Y.; Liu, F.; Xu, Y. Protective effect of β-glucogallin on damaged cataract against methylglyoxal induced oxidative stress in cultured lens epithelial cells. Med. Sci. Monit. 2019, 25, 9310–9318. [Google Scholar] [CrossRef]
- Wojnar, W.; Zych, M.; Borymski, S.; Kaczmarczyl-Sedlak, I. Chrysin reduces oxidative stress but does not affect polyol pathway in the lenses of type 1 diabetic rats. Antioxidants 2020, 9, 160. [Google Scholar] [CrossRef]
- Monnier, V.M.; Stevens, V.J.; Cerami, A. Nonenzymatic glycosylation, sulfhydryl oxidation and aggregation of lens proteins in experimental sugar cataracts. J. Exp. Med. 1979, 150, 1098–1107. [Google Scholar] [CrossRef]
- Perry, R.E.; Swamy, M.S.; Abraham, E.C. Progressive changes in lens crystallin glycation and high-molecular-weight aggregate formation leading to cataract development in streptozotocin-diabetic rats. Exp. Eye Res. 1987, 44, 269–282. [Google Scholar] [CrossRef]
- Casey, E.B.; Zhao, H.R.; Abraham, E.C. Role of glycine 1 and lysine 2 in the glycation of bovine gamma B-crystallin. Site-directed mutagenesis of lysine to threonine. J. Biol. Chem. 1995, 270, 20781–20786. [Google Scholar] [CrossRef]
- Kumar, P.A.; Kumar, M.S.; Reddy, G.B. Effect of glycation on alpha-crystallin structure and chaperone-like function. Biochem. J. 2007, 408, 251–258. [Google Scholar] [CrossRef]
- Bejarano, E.; Taylor, A. Too sweet: Problems of protein glycation in the eye. Exp. Eye Res. 2019, 178, 255–262. [Google Scholar] [CrossRef] [PubMed]
- Stitt, A.W. The Maillard reaction in eye diseases. Ann. N. Y. Acad. Sci. 2005, 1043, 582–597. [Google Scholar] [CrossRef]
- Groenen, P.J.; Merck, K.B.; Jong, W.W.; Bloemendal, H. Structure and modifications of the junior chaperone alpha-crystallin. From lens transparency to molecular pathology. Eur. J. Biochem. 1994, 225, 1–19. [Google Scholar] [CrossRef]
- Kilhovd, B.K.; Berg, T.J.; Birkeland, K.I.; Thorsby, P.; Hanssen, K.F. Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease. Diabetes Care 1999, 22, 1543–1548. [Google Scholar] [CrossRef]
- Wautier, M.P.; Massin, P.; Guillausseau, P.J.; Huijberts, M.; Levy, B.; Boulanger, E.; Laloi-Michelin, M.; Wautier, J.L. N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients. Diabetes Metab. 2003, 29, 44–52. [Google Scholar] [CrossRef]
- Nagaraj, R.H.; Sady, C. The presence of a glucose-derived Maillard reaction product in the human lens. FEBS Lett. 1996, 382, 234–238. [Google Scholar] [CrossRef]
- Dunn, J.A.; Patrick, J.S.; Thorpe, S.R.; Baynes, J.W. Oxidation of glycated proteins: Age-dependent accumulation of N-(carboxymethyl) lysine in lens proteins. Biochemistry 1989, 28, 9464–9468. [Google Scholar] [CrossRef]
- Zarina, S.; Zhao, H.R.; Abraham, E.C. Advanced glycation end products in human senile and diabetic cataractous lenses. Mol. Cell. Biochem. 2000, 210, 29–34. [Google Scholar] [CrossRef]
- Pokupec, R.; Kalauz, M.; Turk, N.; Turk, Z. Advanced glycation endproducts in human diabetic and non-diabetic cataractous lenses. Graefe’s Arch. Clin. Exp. Ophthalmol. 2003, 241, 378–384. [Google Scholar] [CrossRef]
- Franke, S.; Dawczynski, J.; Strobel, J.; Niwa, T.; Stahl, P.; Stein, G. Increased levels of advanced glycation end products in human cataractous lenses. J. Cataract. Refract. Surg. 2003, 29, 981004. [Google Scholar] [CrossRef]
- Hashim, Z.; Zarina, S. Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract. Age 2011, 33, 377–384. [Google Scholar] [CrossRef] [PubMed]
- Taylor, A. Associations between nutrition and cataract. Nutr. Rev. 1989, 47, 225–234. [Google Scholar] [CrossRef] [PubMed]
- Blondin, J.; Baragi, V.; Schwartz, E.; Sadowski, J.A.; Taylor, A. Delay of UV-induced eye lens protein damage in guinea pigs by dietary ascorbate. J. Free Radic. Biol. Med. 1986, 2, 275–281. [Google Scholar] [CrossRef] [PubMed]
- Wei, L.; Liang, G.; Cai, C.; Lv, J. Association of vitamin C with the risk of age-related cataract: A meta-analysis. Acta Ophthalmol. 2016, 94, e170–e176. [Google Scholar] [CrossRef]
- Kim, J.H.; Na, H.J.; Kim, C.K.; Kim, J.Y.; Ha, K.S.; Lee, H.; Chung, H.T.; Kwon, H.J.; Kwon, Y.G.; Kim, Y.M. The non-provitamin A carotenoid, lutein, inhibits HF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathway: Role of H2O2 in NF-kappaB activation. Free Radic. Biol. Med. 2008, 45, 885–896. [Google Scholar] [CrossRef]
- Moeller, S.M.; Voland, R.; Tinker, L.; Blodi, B.A.; Klein, M.L.; Gehrs, K.M.; Johnson, E.J.; Snodderly, D.M.; Wallace, R.B.; Chappell, R.J.; et al. Association between age- related nuclear cataract and lutein and zeaxanthin in the diet and serum in the carotenoid in the Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women’s Health Initiative. Arch Ophthalmol. 2008, 126, 354–364. [Google Scholar] [CrossRef]
- Christen, W.G.; Liu, S.; Glynn, R.J.; Gaziano, J.M.; Buring, J.E. Dietary carotenoids, vitamins C and, D.; and risk of cataract in women: A prospective study. Arch Ophthalmol. 2008, 126, 102–109. [Google Scholar] [CrossRef]
- Jiang, H.; Yin, Y.; Wu, C.R.; Liu, Y.; Guo, F.; Li, M.; Ma, L. Dietary vitamin and carotenoid intake and risk of age-related cataract. Am. J. Clin. Nutr. 2019, 109, 43–54. [Google Scholar] [CrossRef]
- Hayashi, R.; Hayashi, S.; Arai, K.; Sakai, M.; Okamoto, H.; Chikuda, M. The gender-differentiated antioxidant effects of a lutein-containing supplement in the aqueous humor of patients with senile cataracts. Exp. Eye Res. 2014, 129, 5–12. [Google Scholar] [CrossRef]
- Stadtman, E.R. Protein oxidation and aging. Science 1992, 257, 1220–1224. [Google Scholar] [CrossRef]
- Finkel, T.; Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature 2000, 408, 239–247. [Google Scholar] [CrossRef] [PubMed]
- Uribarri, J.; Cai, W.; Peppa, M.; Goodman, S.; Ferrucci, L.; Striker, G.; Vlassara, H. Circulating glycotoxins and dietary advanced glycation endproducts: Two links to inflammatory response, oxidative stress, and aging. J. Gerontol. A Biol. Sci. Med. Sci. 2007, 62, 427–433. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Kho, A.; Anilkumar, N.; Chibber, R.; Pagano, P.J.; Shah, A.M.; Cave, A.C. Glycated proteins stimulate reactive oxygen species production in cardiac myocytes: Involvement of Nox2 (gp91phox)-containing NADPH oxidase. Circulation 2006, 113, 1235–1243. [Google Scholar] [CrossRef] [PubMed]
- Guimaraes, E.; Empsen, C.; Geerts, A.; van Grunsven, L.A. Advanced glycation end products induce production of reactive oxygen species via the activation of NADPH oxidase in murine hepatic stellate cells. J. Hepatol. 2010, 52, 389–397. [Google Scholar] [CrossRef] [PubMed]
- Lin, N.; Zhang, H.; Su, Q. Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress. Diabetes Metab. 2012, 38, 250–257. [Google Scholar] [CrossRef]
- Moldogazieva, N.T.; Mokhosoev, I.M.; Mel’nikova, T.I.; Porozov, Y.B.; Terentiev, A.A. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxidative Med. Cell. Longev. 2019, 2019, 3085756. [Google Scholar] [CrossRef]
- Yao, D.; Brownlee, M. Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes 2010, 59, 249–255. [Google Scholar] [CrossRef]
- Hayashi, R.; Hayashi, S.; Arai, K.; Chikuda, M.; Obara, Y. Effects of antioxidant supplementation on mRNA expression of glucose-6-phosphate dehydrogenase, β-actin and 18S rRNA in the anterior capsule of the lens in cataract patients. Exp. Eye Res. 2012, 96, 48–54. [Google Scholar] [CrossRef]
- Hayashi, R.; Hayashi, S.; Sakai, M.; Arai, K.; Chikuda, M.; Machida, S. Gender differences in mRNA expression of aquaporin 8 and glutathione peroxidase in cataractous lens following intake of an antioxidant supplement. Exp. Eye Res. 2018, 168, 28–32. [Google Scholar] [CrossRef]
- Franke, S.; Stein, F.; Dawczynski, J.; Blum, M.; Kubetschka, U.; Stein, G.; Strobel, J. Advanced glycation end-products in anterior chamber aqueous of cataractous patients. J. Cataract. Refract. Surg. 2003, 29, 329–335. [Google Scholar] [CrossRef]
- Chitra, P.S.; Chaki, D.; Boiroju, N.K.; Mokalla, T.R.; Gadde, A.K.; Agraharam, S.G.; Reddy, G.B. Status of oxidative stress markers, advanced glycation index, and polyol pathway in age-related cataract subjects with and without diabetes. Exp. Eye Res. 2020, 200, 108230. [Google Scholar] [CrossRef] [PubMed]
- Reddy, G.B.; Satyanarayana, A.; Balakrishna, N.; Ayyagari, R.; Padma, M.; Viswanath, K.; Petrash, J.M. Erythrocyte aldose reductase activity and sorbitol levels in diabetic retinopathy. Mol. Vis. 2008, 14, 593–601. [Google Scholar] [PubMed]
- Loho, T.; Venna, V.; Setiabudy, R.D.; Sukartini, N.; Immanuel, S.; Kumalawati, J.; Victor, A.A.; Waspadji, S. Correlation between vitreous advanced glycation end products, and D-dimer with blood HbA1c levels in proliferative diabetic retinopathy. Acta Medica Indones. 2018, 50, 132–137. [Google Scholar]
- Hirai, T.; Fujiyoshi, K.; Yamada, S.; Matsumoto, T.; Kikuchi, J.; Ishida, K.; Ishida, M.; Yamaoka-Tojo, M.; Inomata, T.; Shigeta, K.; et al. Advanced glycation end products are associated with diabetes status and physical functions inpatients with cardiovascular disease. Nutrients 2022, 14, 3032. [Google Scholar] [CrossRef]
- Christidis, G.; Küppers, F.; Karatayli, S.C.; Karatayli, E.; Weber, S.N.; Lammert, F.; Krawczyk, M. Skin advanced glycation end-products as indicators of the metabolic profile in diabetes mellitus: Correlations with glycemic control, liver phenotypes and metabolic biomarkers. BMC Endocr. Disord. 2024, 24, 31. [Google Scholar] [CrossRef]
- Cai, W.; He, J.C.; Zhu, L.; Chen, X.; Wallenstein, S.; Striker, G.E.; Vlassara, H. Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: Association with increased AGER1 expression. Am. J. Pathol. 2007, 170, 1893–1902. [Google Scholar] [CrossRef]
- Hayashi, R.; Hayashi, S.; Machida, S. Changes in macular pigment optical density among pseudophakic patients following intake of a lutein-containing supplement. Ophthalmic Res. 2021, 64, 828–836. [Google Scholar] [CrossRef]
- Mooradian, A.D.J. Antioxidant properties of steroids. Steroid Biochem. Mol. Biol. 1993, 45, 509–511. [Google Scholar] [CrossRef]
- Gómez-Zubeldia, M.A.; Arbués, J.J.; Hinchado, G.; Nogales, A.G.; Millán, J.C. Influence of estrogen replacement therapy on plasma lipid peroxidation. Menopause 2001, 8, 274–280. [Google Scholar] [CrossRef]
- Ruiz-Larrea, M.B.; Martín, C.; Martínez, R.; Navarro, R.; Lacort, M.; Miller, N.J. Antioxidant activities of estrogens against aqueous and lipophilic radicals; differences between phenol and catechol estrogens. Chem. Phys. Lipids 2000, 105, 179–188. [Google Scholar] [CrossRef]
- Borras, C.; Gambini, J.; Gomez-Cabrera, M.C.; Sastre, J.; Pallardo, F.V.; Mann, G.E.; Vina, J. 17β-Oestradiol up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2(MAPK)/NFκB cascade. Aging Cell 2005, 4, 113–118. [Google Scholar] [CrossRef] [PubMed]
- Frei, B.; Stocker, R.; Ames, B.N. Antioxidant defences and lipid peroxidation in human blood plasma. Proc. Natl. Acad. Sci. USA 1988, 85, 9748–9752. [Google Scholar] [CrossRef] [PubMed]
- Levine, M. New concepts in the biology and biochemistry of ascorbic acid. N. Engl. J. Med. 1986, 314, 892–902. [Google Scholar] [CrossRef]
- Machlin, L.J.; Bendich, A. Free radical tissue damage: Protective role of antioxidant nutrients. FASEB J. 1987, 1, 441–445. [Google Scholar] [CrossRef]
- Offord, E.A.; Gautier, J.C.; Avanti, O.; Scaletta, C.; Runge, F.; Krämer, K.; Applegate, L.A. Photoprotective potential of lycopene, beta-carotene, vitamin, E.; vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts. Free. Radic. Biol. Med. 2002, 32, 1293–1303. [Google Scholar] [CrossRef]
- Wefers, H.; Sies, H. The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin, E. Eur. J. Biochem. 1988, 174, 353–357. [Google Scholar] [CrossRef]
- Leske, M.C.; Chylack, L.T., Jr.; Wu, S. The lens opacities case-control study risk factors for cataract. Arch. Ophthalmol. 1991, 109, 244–251. [Google Scholar] [CrossRef]
- Seddon, J.M.; Christen, W.G.; Manson, J.E.; LaMotte, F.S.; Glynn, R.J.; Buring, J.E.; Hennekens, C.H. The use of vitamin supplements and the risk of cataract among US male physician. Am. J. Public Health 1994, 84, 788–792. [Google Scholar] [CrossRef]
- Knekt, P.; Heliövaara, M.; Rissanen, A.; Aromaa, A.; Aaran, R.K. Serum antioxidants vitamins and risk of cataract. Br. Med. J. 1992, 305, 1392–1394. [Google Scholar] [CrossRef]
- Hayashi, R.; Hayashi, S.; Machida, S. Changes in aqueous humor lutein levels of patients with cataracts after a 6-week course of lutein-containing antioxidant supplementation. Curr. Eye Res. 2022, 47, 1016–1023. [Google Scholar] [CrossRef]
- Chylack, L.T., Jr.; Wolfe, J.K.; Singer, D.M.; Leske, M.C.; Bullimore, M.A.; Bailey, I.L.; Friend, J.; McCarthy, D.; Wu, S.Y. The lens opacities classification system III. The longitudinal study of cataract study group. Arch Ophthalmol. 1993, 111, 831–836. [Google Scholar] [CrossRef] [PubMed]
Age-Matched Control * | DM Group | p | ||
---|---|---|---|---|
No. | males | 45 | 10 | |
females | 55 | 15 | ||
Age (y/o) | males | 74.9 ± 5.5 | 74.4 ± 5.7 | n.s |
females | 74.3 ± 5.1 | 75.1 ± 5.9 | n.s | |
Pre-intake CML (ng/mL) | males | 155.2 ± 41.0 | 163.1 ± 54.9 | n.s |
females | 162.9 ± 29.4 | 158.2 ± 34.8 | n.s | |
Post-intake CML (ng/mL) | males | 162.1 ± 47.1 | 134.9 ± 27.7 | n.s |
females | 163.1 ± 28.0 | 142.0 ± 23.5 | n.s | |
Pre-intake SOD (U/mL) | males | 21.2 ± 3.5 | 13.7 ± 2.3 | <0.0001 |
females | 20.5 ± 4.0 | 13.3 ± 1.6 | 0.0001 | |
Post-intake SOD (U/mL) | males | 25.2 ± 4.0 | 12.8 ± 2.5 | <0.0001 |
females | 23.0 ± 3.2 | 11.7 ± 2.0 | <0.0001 | |
Pre-intake TH (CARR) | males | 1.3 ± 0.2 | 2.0 ± 0.3 | 0.0345 |
females | 2.1 ± 0.3 | 2.2 ± 0.3 | n.s | |
Post-intake TH (CARR) | males | 0.6 ± 0.2 | 2.4 ± 1.3 | 0.0016 |
females | 1.3 ± 0.2 | 1.9 ± 0.2 | 0.0153 |
Substance | Amount |
---|---|
lutein | 6.0 mg |
vitamin C | 300.0 mg |
vitamin E | 60.0 mg |
vitamin B2 | 3.0 mg |
β-carotene | 1200.0 μg |
niacin | 12.0 mg |
zinc | 9.0 mg |
selenium | 45.0 μg |
copper | 0.6 mg |
manganese | 1.5 mg |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 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
Hayashi, R.; Hayashi, S.; Machida, S. The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts. Int. J. Mol. Sci. 2025, 26, 5706. https://doi.org/10.3390/ijms26125706
Hayashi R, Hayashi S, Machida S. The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts. International Journal of Molecular Sciences. 2025; 26(12):5706. https://doi.org/10.3390/ijms26125706
Chicago/Turabian StyleHayashi, Rijo, Shimmin Hayashi, and Shigeki Machida. 2025. "The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts" International Journal of Molecular Sciences 26, no. 12: 5706. https://doi.org/10.3390/ijms26125706
APA StyleHayashi, R., Hayashi, S., & Machida, S. (2025). The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts. International Journal of Molecular Sciences, 26(12), 5706. https://doi.org/10.3390/ijms26125706