Effects of N-acetylcysteine and glutathione ethyl ester drops on streptozotocin-induced diabetic cataract in rats.
OBJECTIVE
To evaluate the effect of N-acetylcysteine (NAC) and glutathione ethyl ester (GSH-EE) eye drops on the progression of diabetic cataract formation induced by streptozotocin (STZ).


METHODS
One hundred and thirty Sprague-Dawley (SD) rats were selected, and diabetes was induced by streptozotocin (65 mg/kg bodyweight) in a single intraperitoneal injection. The control group (group I) received only vehicle. Then, 78 rats with random blood glucose above 14 mmol/l were divided into four groups (group II-V). The drug-treated rats received NAC and GSH-EE eye drops five days before STZ injection. Group I and V animals received sodium phosphate buffer drops (pH 7.4), and those in groups II, III, and IV received 0.01% NAC, 0.05% NAC, and 0.1% GSH-EE drops, respectively. Lens transparency was monitored with a slit lamp biomicroscope and classified into six stages. At the end of four weeks, eight weeks, and 13 weeks, animals were killed and components involved in the pathogenesis of diabetic cataract including thiols (from glutathione and protein), glutathione reductase (GR), catalase (CAT), and glycated proteins were investigated in the lens extracts. Blood glucose, urine glucose, and bodyweight were also determined.


RESULTS
The progression in lens opacity induced by diabetes showed a biphasic pattern in which an initial slow increase in the first seven weeks after STZ injection was followed by a rapid increase in the next six weeks. The progression of lens opacity in the treated groups (group II-IV) was slower than that of the untreated group (group V) in the earlier period and especially in the fourth week. There were statistically significant differences between the treated groups and the untreated group (p<0.05). However, these differences became insignificant after the sixth week, and the progression of lens opacification in all diabetic groups became aggravated. The content of thiol (from glutathione and protein), glutathione reductase (GR), and catalase (CAT) were lower in the lens extracts of the diabetic rats four weeks, eight weeks, and 13 weeks after the STZ injection while the levels of thiol and CAT activity were both higher in the treated groups (group II-IV) than in the untreated group (group V) at every stage. However, there was no statistically significant difference (p>0.05). Moreover, the diabetes resulted in an increased level of glycated proteins in both the treated groups and the untreated group, but there was no statistically significant difference between all the diabetic groups (p>0.05).


CONCLUSIONS
NAC and GSH-EE can slightly inhibit the progression of the diabetic cataract at the earlier stage. They may maintain lens transparency and function by serving as a precursor for glutathione biosynthesis and by protecting sulfhydryl groups from oxidation.
Zhang
Shu
S
Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Chai
Fei-Yan
FY
Yan
Hong
H
Guo
Yong
Y
Harding
J J
JJ
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002386:Cataract / Q000150:complications* / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000201:enzymology; D005136:Eye Proteins / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D005980:Glutathione Reductase / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D007267:Injections; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility / Q000187:drug effects; D013311:Streptozocin; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014867:Water / Q000378:metabolism
D001786:Blood Glucose; D005136:Eye Proteins; D009883:Ophthalmic Solutions; D013438:Sulfhydryl Compounds; D014867:Water; D013311:Streptozocin; C042431:S-ethyl glutathione; D002374:Catalase; D005980:Glutathione Reductase; D005978:Glutathione; D000111:Acetylcysteine