Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats

Abstract

Purpose: The purpose of this paper was to investigate the effect of the oral administration of L-glycine (Gly) on the development of diabetic cataract induced by streptozotocin (STZ) in rats.

Methods: Two groups of male Wistar rats were intraperitoneally injected with a single dose of STZ (65 mg/kg bodyweight). Then, one group of diabetic rats and a control group were administered with 1% of Gly in drinking water for three months, ad libitum. Cataract development was monitored biweekly through ophthalmoscope inspection and was classified into four stages. At the end of 12 weeks, the animals were sacrificed and some biochemical parameters were determined in their lenses. The parameters include advanced glycation end products (AGEs), glycated proteins, total and soluble protein, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), aldose reductase (AR), and sorbitol dehydrogenase (SDH). Some parameters were also determined in the serum and blood of the rats.

Results: Diabetic cataract gradually progressed in the STZ-administered group with no other treatment. Consequently, up to the end of the experiment, 2/3 of the animals in this group reached to the last stage of the cataract (mature cataract). The progress of this process was much slower in the diabetic group that was treated with Gly. At the end of the study, the visual cataract score was significantly lower in the diabetic group treated with Gly compared to those administered with STZ. Some lens parameters, including glycated proteins, AGEs, SOD, and AR activities, were increased while some others, including soluble and total protein, GSH level, and CAT activity, were decreased due to diabetes induction. After Gly treatment, all the above-named parameters had reverse changes except for the CAT activity. The SDH activity in the lenses had no changes due to diabetes or treatment. In addition, this treatment significantly decreased the amount of serum glucose (Glc), serum AGEs, and glycated hemoglobin (HbA1c) in the diabetic rats. Gly also increased the ferric reducing antioxidant power (FRAP) in the serum of diabetic rats. However, the decreased bodyweight of animals due to diabetes induction was not compensated by Gly administration. It is important to note that Gly had no effect on normal rat parameters.

Conclusions: The results indicated that the oral administration of Gly significantly delayed the onset and the progression of diabetic cataract in rats. These effects were due to its antiglycating action and to a lesser extent, due to the inhibition of oxidative stress and polyol pathway.

Figure 1

Changes in the rat’s bodyweight during the course of the experiment. The data shows the average results in all the animals in a given group at a given time. The weights of the normal groups were significantly different from those of the diabetic groups (p<0.01) and there were no significant differences between the two diabetic groups at any time. N: normal rats; D: diabetic rats; DG: diabetic rats with Gly; and NG: normal rats with Gly.

Figure 2

Changes in the serum and blood biochemical parameters in different groups of rats at the different times of the experiment. A: Glucose concentration, B: Percent of HbA1c, C: Fluorescence intensity of AGEs, and D: FRAP. N: normal rats; D: diabetic rats; DG: diabetic rats with Gly; and NG: normal rats with Gly. “a” indicates the significance of the data that compares group N versus all groups. “b” indicates the significance of the data that compares group D versus groups of glycine-treated rats. *, p<0.05; #, p<0.01; and †, p<0.001.

Figure 3

Effect of Gly therapy on the opacity of the lenses in STZ-diabetic rats. A: Photographs of lenses from each group at the end of 12 weeks. B: Progression of cataract in diabetic rats throughout the experimental period. Cataract formation was scored biweekly according to the following classification: clear normal lens (O), peripheral vesicles (I), peripheral vesicles and cortical opacities (II), diffuse central opacities (III) and mature cataract (IV). The scores of cataracts in each group were averaged at the given time and the average score of the cataract was plotted as a function of time. There was a significant difference (p<0.001) between the average score of the cataract of groups D and DG from six weeks to the end of the study. C: Maturation of the cataract in diabetic rats after 12 weeks. Cataract development in rats was observed on week 12 of the study and the number of lenses that developed opacity against the total number of lenses was considered for calculating the percentage of incidence of cataract in each group. N: normal rats; D: diabetic rats; DG: diabetic rats with Gly; and NG: normal rats with Gly.