Офтальмохирургия. 2015; : 10-12
Analysis of lens redox status in cataracts from rat models of type 1 and 2 diabetes
https://doi.org/undefinedАннотация
Цель. Определить дифференциальные изменения окислительно-восстановительного статуса при формировании диабетической катаракты (ДК) 1-го типа (T1ДК) и 2-го типа (T2ДК) на крысах.
Материал и методы. У крыс были воспроизведены модели диабета 1-го и 2-го типа, обследования по поводу прогрессирования катаракты проводились еженедельно. К восьмой неделе снижались уровни активности восстановленного глутатиона (GSH), окисленного глутатиона (GSSG), никотинамид-аденин-динуклеотид 2-фосфата (NADPH) и глюкозо-6-фосфата дегидрогеназы (G6PD). Данные сравнивались с таковым в контрольной группе.
Результаты. Катаракты появились на две недели раньше у крыс с диабетом 1-го типа по сравнению с диабетом 2-го типа. Кроме того, катаракты прогрессировали медленнее при T2ДК по сравнению с T1ДК. Уровни GSH хрусталика были снижены у крыс с диабетом 1-го типа в 4 раза и в 2 раза – с диабетом 2-го типа, по сравнению с уровнями у крыс контрольной группы. Уровни NADPH у крыс с диабетом при 1-м и 2-м типе были снижены в 2,4 и 1,5 раза соответственно по сравнению с контрольной группой. Подобные изменения были выявлены и при определении активности G6PD.
Заключение. Полученные результаты свидетельствуют о том, что снижение GSH и NADPH может быть важным патологическим механизмом в формировании T1ДК и T2ДК. «Быстрое» прогрессирование катаракты у крыс с диабетом 1-го типа может быть следствием более тяжелого окислительного стресса, чем у крыс с диабе том 2-го типа.
Список литературы
1. Dovrat A., Gershon D. Rat lens superoxide dismutase and glucose-6- phosphate dehydrogenase: studies on the catalytic activity and the fate of enzyme antigen as a function of age // Exp. Eye Res. – 1981. – Vol. 33. – P. 651-661.
2. Falck A., Laatikainen L. Diabetic cataract in children // Acta Ophthalmol. Scand. – 1998. – Vol. 76. – P. 238-240.
3. Ganea E., Harding J.J. Glutathionerelated enzymes and the eye // Curr. Eye Res. – 2006. – Vol. 31. – P. 1-11.
4. Giblin F.J., Reddy V.N. Pyridine nucleotides in ocular tissues as determined by the cycling assay // Exp. Eye Res. – 1980. – Vol. 31. – P. 601-609.
5. Hashim Z., Zarina S. Osmotic stress induced oxidative damage: possible mechanism of cataract formation in diabetes // J. Diabetes Complications. – 2012. – Vol. 26. – P. 275-279.
6. Heo M., Kim E. Effects of endurance training on lipid metabolism and glycosylated hemoglobin levels in streptozotocin-induced type 2 diabetic rats on a high-fat diet // J. Phys. Ther. Sci. – 2013. – Vol. 25. – P. 989-992.
7. Lou M.F., Dickerson J.E., Garadi R., York B.M. Glutathione depletion in the lens of galactosemic and diabetic rats // Exp. Eye Res. – 1988. – Vol. 46. – P. 517-530.
8. Mitton K.P., Trevithick J.R. Highperformance liquid chromatographyelectrochemical detection of antioxidants in vertebrate lens: glutathione, tocopherol, and ascorbate // Methods Enzymol. – 1994. – Vol. 233. – P. 523-539.
9. Mokrasch L.C., Teschke E.J. Glutathione content of cultured cells and rodent brain regions: a specific fluorometric assay // Anal Biochem. – 1984. – Vol. 140. – P. 506-509.
10. Obrosova I.G. Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications // Antioxid. Redox Signal. – 2005. – Vol. 7. – P. 1543-1552.
11. Obrosova I., Cao X., Greene D.A., Stevens M.J. Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DLalpha- lipoic acid // Diabetologia. – 1998. – Vol. 41. – P. 1442-1450.
12. Obrosova I.G., Stevens M.J. Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens // Invest. Ophthalmol. Vis. Sci. – 1999. – Vol. 40. – P. 680-688.
13. Olofsson E.M., Marklund S.L., Behndig A. Enhanced diabetes-induced cataract in copper-zinc superoxide dismutase-null mice // Invest. Ophthalmol. Vis. Sci. – 2009. – Vol. 50. – P. 2913-2918.
14. Pintor J. Sugars, the crystalline lens and the development of cataracts // Biochem Pharmacol. – 2012. – Vol. 1. – P. 119.
15. Rathbun W.B., Schmidt A.J., Holleschau A.M. Activity loss of glutathione synthesis enzymes associated with human subcapsular cataract // Invest Ophthalmol. Vis. Sci. – 1993. – Vol. 34. – P. 2049-2054.
16. Reed M.J., Meszaros K., Entes L.J. et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat // Metabolism. – 2000. – Vol. 49. – P. 1390-1394.
Fyodorov Journal of Ophthalmic Surgery. 2015; : 10-12
Analysis of lens redox status in cataracts from rat models of type 1 and 2 diabetes
https://doi.org/undefinedAbstract
Purpose. To identify differential changes in redox status underlying type 1 (T1DC) and type 2 (T2DC) diabetic cataract (DC) formation in rat.
Material and methods. Rat models of type 1 and 2 diabetes were respectively induced, and cataract progression was examined weekly. At week eight the levels of reduced glutathione (GSH), oxidized glutathione (GSSG), nicotinamide adenine dinucleotide 2’-phosphate reduced tetrasodium salt (NADPH), and glucose-6-phosphate dehydrogenase (G6PD) activity were measured and compared with those in controls.
Results. Cataracts were observed two more weeks earlier in type 1 than type 2 diabetic rats. Furthermore, cataracts were progressed more slowly in T2DC compared with those in T1DC. Lens GSH levels were decreased 4-fold and 2-fold in type 1 and type 2 diabetic rats, respectively, compared with levels in normal control rats. NADPH levels were showed 2.4-fold and 1.5-fold decreases in type 1 and 2 diabetic rats, respectively, compared with normal controls. Similar changes were found in the activity of G6PD.
Conclusions. The results suggest that GSH and NADPH loss might be important pathological mechanisms in T1DC and T2DC formation. The «fast» progression of cataracts in type 1 diabetic rats might be due to the more severe oxidative stress than in type 2 diabetic rats.
References
1. Dovrat A., Gershon D. Rat lens superoxide dismutase and glucose-6- phosphate dehydrogenase: studies on the catalytic activity and the fate of enzyme antigen as a function of age // Exp. Eye Res. – 1981. – Vol. 33. – P. 651-661.
2. Falck A., Laatikainen L. Diabetic cataract in children // Acta Ophthalmol. Scand. – 1998. – Vol. 76. – P. 238-240.
3. Ganea E., Harding J.J. Glutathionerelated enzymes and the eye // Curr. Eye Res. – 2006. – Vol. 31. – P. 1-11.
4. Giblin F.J., Reddy V.N. Pyridine nucleotides in ocular tissues as determined by the cycling assay // Exp. Eye Res. – 1980. – Vol. 31. – P. 601-609.
5. Hashim Z., Zarina S. Osmotic stress induced oxidative damage: possible mechanism of cataract formation in diabetes // J. Diabetes Complications. – 2012. – Vol. 26. – P. 275-279.
6. Heo M., Kim E. Effects of endurance training on lipid metabolism and glycosylated hemoglobin levels in streptozotocin-induced type 2 diabetic rats on a high-fat diet // J. Phys. Ther. Sci. – 2013. – Vol. 25. – P. 989-992.
7. Lou M.F., Dickerson J.E., Garadi R., York B.M. Glutathione depletion in the lens of galactosemic and diabetic rats // Exp. Eye Res. – 1988. – Vol. 46. – P. 517-530.
8. Mitton K.P., Trevithick J.R. Highperformance liquid chromatographyelectrochemical detection of antioxidants in vertebrate lens: glutathione, tocopherol, and ascorbate // Methods Enzymol. – 1994. – Vol. 233. – P. 523-539.
9. Mokrasch L.C., Teschke E.J. Glutathione content of cultured cells and rodent brain regions: a specific fluorometric assay // Anal Biochem. – 1984. – Vol. 140. – P. 506-509.
10. Obrosova I.G. Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications // Antioxid. Redox Signal. – 2005. – Vol. 7. – P. 1543-1552.
11. Obrosova I., Cao X., Greene D.A., Stevens M.J. Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DLalpha- lipoic acid // Diabetologia. – 1998. – Vol. 41. – P. 1442-1450.
12. Obrosova I.G., Stevens M.J. Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens // Invest. Ophthalmol. Vis. Sci. – 1999. – Vol. 40. – P. 680-688.
13. Olofsson E.M., Marklund S.L., Behndig A. Enhanced diabetes-induced cataract in copper-zinc superoxide dismutase-null mice // Invest. Ophthalmol. Vis. Sci. – 2009. – Vol. 50. – P. 2913-2918.
14. Pintor J. Sugars, the crystalline lens and the development of cataracts // Biochem Pharmacol. – 2012. – Vol. 1. – P. 119.
15. Rathbun W.B., Schmidt A.J., Holleschau A.M. Activity loss of glutathione synthesis enzymes associated with human subcapsular cataract // Invest Ophthalmol. Vis. Sci. – 1993. – Vol. 34. – P. 2049-2054.
16. Reed M.J., Meszaros K., Entes L.J. et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat // Metabolism. – 2000. – Vol. 49. – P. 1390-1394.
