Anti-oxidant status in an in vitro model for hyperglycaemic lens cataract formation: competition for available nicotinamide adenine dinucleotide phosphate between glutathione reduction and the polyol pathway.
The level of NADPH, total glutathione and sorbitol have been measured in a normal (5mM) and hyperglycaemic (35mM glucose) in vitro rat lens model. In hyperglycaemic conditions, these intermediates are 50%, 84% and 3628% of the normal level. When oxidatively stressed with H2O2 (0.1mM-1.0mM) a gradation in the NADPH and total glutathione decrease is seen, at both glucose levels. This effect is most pronounced in lenses incubated in 35mM glucose, with levels already decreased, the NADPH falls to 15% of the normal lens. Sorbitol levels are correspondingly lower when the lens is oxidatively stressed. The inclusion of the ethyl ester of glutathione alleviates the disruption in anti-oxidant status caused by H2O2 but is unable to restore the NADPH level depleted by hyperglycaemia. These results are discussed in relation to the competitive requirements for NADPH between anti-oxidant preservation and sorbitol formation, as a mechanism for lens opacification in diabetes.
Hothersall
J S
JS
Department of Biochemistry and Molecular Biology, University College and Middlesex School of Medicine, London.
Muirhead
R P
RP
Taylaur
C E
CE
Jones
R H
RH
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002386:Cataract / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D004952:Esters; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000378:metabolism*
D004952:Esters; D013012:Sorbitol; D009249:NADP; D006861:Hydrogen Peroxide; D005978:Glutathione