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Zinc Supplementation Ameliorates Diabetic Cataract Through Modulation of Crystallin Proteins and Polyol Pathway in Experimental Rats

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Abstract

Non-enzymatic glycation of lens proteins and elevated polyol pathway in the eye lens have been the characteristic features of a diabetic condition. We have previously reported the benefits of zinc supplementation in reducing hyperglycemia and associated metabolic abnormalities and oxidative stress in diabetic rats. The current study explored whether zinc supplementation protects against cataractogenesis through modulation of glycation of lens proteins, elevated polyol pathway, oxidative stress, and proportion of different heat shock proteins in the eye lens of diabetic rats. Streptozotocin-induced diabetic rats were fed with a zinc-enriched diet (5 and 10 times of normal) for 6 weeks. Supplemental zinc alleviated the progression and maturation of diabetes-induced cataract. Zinc was also effective in preventing the reduced content of total and imbalanced proportion of soluble proteins in the lens. Supplemental zinc also alleviated cross-linked glycation and concomitant expression of the receptor of glycated products and oxidative stress indicators in the eye lens. Zinc supplementation further induced the concentration of heat shock protein in the eye lens of diabetic rats, specifically α-crystallin. Zinc supplementation counteracted the elevated activity and expression of polyol pathway enzymes and molecules in the lens. The results of this animal study endorsed the advantage of zinc supplementation in exerting the antiglycating influence and downregulating polyol pathway enzymes to defer cataractogenesis in diabetic rats.

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References

  1. Trayhurn P, Heyningen RV (1972) The role of respiration in the energy metabolism of the bovine lens. Biochem J 129:507–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Obrosova IG, Chung SSM, Kador PF (2010) Diabetic cataracts: mechanisms and management. Diabetes Metab Res Rev 26:172–180

    Article  CAS  PubMed  Google Scholar 

  3. Tang WH, Martin KA, Hwa J (2012) Aldose reductase, oxidative stress, and diabetic mellitus. Front Pharmacol 3:87–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hashim Z, Zarina S (2011) Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract. Age 33:377–384

    Article  CAS  PubMed  Google Scholar 

  5. Kumar PA, Reddy GB (2009) Modulation of Α-crystallin chaperone activity: a target to prevent or delay cataract? IUBMB Life 61:485–495

    Article  CAS  PubMed  Google Scholar 

  6. Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi RLDK, Constantine GR, Katulanda P (2012) Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr 4:13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Barman S, Pradeep SR, Srinivasan K (2017) Zinc supplementation mitigates zinc dyshomeostasis in streptozotocin-induced diabetic rats by regulating the expression of zinc transporters. Metallomics 9:1765–1777

    Article  CAS  PubMed  Google Scholar 

  8. Barman S, Srinivasan K (2016) Zinc supplementation alleviates hyperglycemia and associated metabolic abnormalities in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 94:1356–1365

    Article  CAS  PubMed  Google Scholar 

  9. Barman S, Srinivasan K (2017) Attenuation of oxidative stress and cardioprotective effects of zinc supplementation in experimental diabetic rats. Br J Nutr 117:335–350

    Article  CAS  PubMed  Google Scholar 

  10. Barman S, Pradeep SR, Srinivasan K (2018) Beneficial effect of zinc supplementation on diabetic nephropathy in experimental rats. J Nutr Biochem 54:113–129

    Article  CAS  PubMed  Google Scholar 

  11. Huggett AS, Nixon DA (1957) Use of glucose oxidase, peroxidase, and o-dianisidine in determination of blood and urinary glucose. Lancet 273:368–370

    Article  CAS  PubMed  Google Scholar 

  12. Zhang H, Agardh E, Agardh CD (1993) Nitro blue tetrazolium staining: a morphological demonstration of superoxide in the rat retina. Graefes Arch Clin Exp Ophthalmol 231:178–183

    Article  CAS  PubMed  Google Scholar 

  13. LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231

    Article  CAS  PubMed  Google Scholar 

  14. Driver AS, Kodavanti PR, Mundy WR (2000) Age-related changes in reactive oxygen species production in rat brain homogenates. Neurotoxicol Teratol 22:175–181

    Article  CAS  PubMed  Google Scholar 

  15. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  16. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363

    Article  CAS  PubMed  Google Scholar 

  17. Flohé L, Otting F (1984) Superoxide dismutase assays. Methods Enzymol 105:93–104

    Article  PubMed  Google Scholar 

  18. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  19. Flohé L, Günzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121

    Article  PubMed  Google Scholar 

  20. Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490

    Article  CAS  PubMed  Google Scholar 

  21. Warholm M, Guthenberg C, von Bahr C, Mannervik B (1985) Glutathione transferases from human liver. Methods Enzymol 113:499–504

    Article  CAS  PubMed  Google Scholar 

  22. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  23. Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62:3–11

    Article  CAS  PubMed  Google Scholar 

  24. Kim HY, Hwan JOH (1999) Screening of Korean forest plants for rat lens aldose reductase inhibition. Biosci Biotechnol Biochem 63:184–188

    Article  CAS  PubMed  Google Scholar 

  25. Gerlach U, Hiby W (1974) Sorbitol dehydrogenase. In: Methods of enzymatic analysis, vol 2. Academic, New York, pp 569–573

    Chapter  Google Scholar 

  26. Bergmeyer HU, Gruber W (1975) D-Sorbitol. In: Bergmeyer HU (ed) Weinheim, Verlag Chemie, Methods of enzymatic analysis. Academic, New York, pp 1323–1330

    Google Scholar 

  27. Bernt E, Bergmeyer HU (1975) D-Fructose. In: Bergmeyer HU (ed) Weinheim, Verlag Chemie, Methods of enzymatic analysis. Academic, New York, pp 1304–1307

    Google Scholar 

  28. Monnier VM, Cerami A (1981) Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science (New York, NY) 211:491–493

    Article  CAS  Google Scholar 

  29. Kyselova Z, Stefek M, Bauer V (2004) Pharmacological prevention of diabetic cataract. J Diabet Complicat 18:129–140

    Article  CAS  Google Scholar 

  30. Bron AJ, Sparrow J, Brown NA, Harding JJ, Blakytny R (1993) The lens in diabetes. Eye (London) 7:260–275

    Article  Google Scholar 

  31. Kinoshita JH (1990) A thirty year journey in the polyol pathway. Exp Eye Res 50:567–573

    Article  CAS  PubMed  Google Scholar 

  32. Hashim Z, Zarina S (2012) Osmotic stress induced oxidative damage: possible mechanism of cataract formation in diabetes. J Diabet Complicat 26:275–279

    Article  Google Scholar 

  33. Giblin FJ (2000) Glutathione: a vital lens antioxidant. J Ocul Pharmacol Ther 16:121–135

    Article  CAS  PubMed  Google Scholar 

  34. Ganea E, Harding JJ (2006) Glutathione-related enzymes and the eye. Curr Eye Res 31:1–11

    Article  CAS  PubMed  Google Scholar 

  35. Singh R, Barden A, Mori T, Beilin L (2001) Advanced glycation end-products: a review. Diabetologia 44:129–146

    Article  CAS  PubMed  Google Scholar 

  36. Stitt AW (2001) Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol 85:746–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Al-Whaibi MH (2011) Plant heat-shock proteins: a mini review. J King Saud Univ Sci 23:139–150

    Article  Google Scholar 

  38. Feder ME, Hofmann GE (1999) Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 61:243–282

    Article  CAS  PubMed  Google Scholar 

  39. Daugaard M, Rohde M, Jättelä M (2007) The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 581:3702–3710

    Article  CAS  PubMed  Google Scholar 

  40. Wang S-M, Lee Y-C, Ko C-Y, Lai M-D, Lin D-Y, Pao P-C, Chi JY, Hsiao YW, Liu TL, Wang JM (2015) Increase of zinc finger protein 179 in response to CCAAT/enhancer binding protein delta conferring an antiapoptotic effect in astrocytes of Alzheimer’s disease. Mol Neurobiol 51:370–382

    Article  CAS  PubMed  Google Scholar 

  41. Horwitz J (2000) The function of alpha-crystallin in vision. Semin Cell Dev Biol 11:53–60

    Article  CAS  PubMed  Google Scholar 

  42. Horwitz J (2003) Alpha-crystallin. Exp Eye Res 76:145–153

    Article  CAS  PubMed  Google Scholar 

  43. van Boekel MAM, Hoenders HJ (1992) Glycation of crystallins in lenses from aging and diabetic individuals. FEBS J 314:1–4

    Article  Google Scholar 

  44. Kosinski-Collins MS, King J (2003) In vitro unfolding, refolding, and polymerization of human γd crystallin, a protein involved in cataract formation. Protein Sci 12:480–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lou MF (2003) Redox regulation in the lens. Prog Retin Eye Res 22:657–682

    Article  CAS  PubMed  Google Scholar 

  46. Simpanya MF, Ansari RR, Suh KI, Leverenz VR, Giblin FJ (2005) Aggregation of lens crystallins in an in vivo hyperbaric oxygen guinea pig model of nuclear cataract: dynamic light-scattering and HPLC analysis. Invest Ophthalmol Vis Sci 46:4641–4651

    Article  PubMed  Google Scholar 

  47. Biswas A, Das KP (2008) Zn2+ enhances the molecular chaperone function and stability of α-crystallin. Biochemistry 47:804–816

    Article  CAS  PubMed  Google Scholar 

  48. Fukiage C, Nakajima E, Ma H, Azuma M, Shearer TR (2002) Characterization and regulation of lens-specific calpain Lp82. J Biol Chem 277:20678–20685

    Article  CAS  PubMed  Google Scholar 

  49. Kilic F, Trevithick JR (1998) Modelling cortical cataractogenesis. XXIX. Calpain proteolysis of lens fodrin in cataract. Biochem Mol Biol Int 45:963–978

    CAS  PubMed  Google Scholar 

  50. Sakamoto-Mizutani K, Fukiage C, Tamada Y, Azuma M, Shearer TR (2002) Contribution of ubiquitous calpains to cataractogenesis in the spontaneous diabetic WBN/Kob rat. Exp Eye Res 75:611–617

    Article  CAS  PubMed  Google Scholar 

  51. Biswas S, Harris F, Dennison S, Singh J, Phoenix DA (2004) Calpains: targets of cataract prevention? Trends Mol Med 10:78–84

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The first author (SB) is grateful to the University Grants Commission, Government of India, New Delhi, for the award of Senior Research Fellowship.

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Authors and Affiliations

  1. Department of Biochemistry, CSIR – Central Food Technological Research Institute, Mysore, 570 020, India

    Susmita Barman & Krishnapura Srinivasan

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  1. Susmita Barman
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  2. Krishnapura Srinivasan
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Correspondence to Krishnapura Srinivasan.

Ethics declarations

The experimental protocol in this animal study was legitimated with due authorization from the Institutional Animal Ethics Committee (CSIR-CFTRI, Mysore, India) and precautions were taken to lessen pain and discomfort to the animals.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Barman, S., Srinivasan, K. Zinc Supplementation Ameliorates Diabetic Cataract Through Modulation of Crystallin Proteins and Polyol Pathway in Experimental Rats. Biol Trace Elem Res 187, 212–223 (2019). https://doi.org/10.1007/s12011-018-1373-3

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