Modelling cortical cataractogenesis. 13. Early effects on lens ATP/ADP and glutathione in the streptozotocin rat model of the diabetic cataract.
A possible contribution to cell toxicity in the diabetic lens due to early ATP loss is not well characterized prior to the appearance of vacuoles in the lens. Changes in lens ATP levels at longer periods of hyperglycaemia (6-8 weeks) have been reported. We used [31P]NMR analysis of lens extracts at three time periods, comparing diabetic to concurrent control groups at 1, 2 and 4 weeks of hyperglycaemia. With this design, significant alterations (> 10%) in the ATP/ADP ratio can be monitored. NMR analysis revealed a decreased ATP/ADP ratio at all time periods, averaging a 38% decrease. Luminescent determination of ATP levels indicates that this decrease is mainly caused by a decrease of 25% in ATP concentration. The early loss of GSH was large and not accompanied by an appearance of GSSG, as monitored by HPLC electrochemical detection. A 1-week experiment with animals receiving daily insulin treatment was carried out to control for effects of STZ on the lens. This treatment resulted in normal lens GSH levels and a near normal [31P]NMR profile.
Mitton
K P
KP
Department of Biochemistry, University of Western Ontario, London, Canada.
Dean
P A
PA
Dzialoszynski
T
T
Xiong
H
H
Sanford
S E
SE
Trevithick
J R
JR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002386:Cataract / Q000209:etiology* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D007328:Insulin / Q000627:therapeutic use; D007908:Lens, Crystalline / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007328:Insulin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005978:Glutathione