The Protective Effect of Vanadium Against Diabetic Cataracts in Diabetic Rat Model
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- Sun, L., Shi, D., Gao, X. et al. Biol Trace Elem Res (2014) 158: 219. doi:10.1007/s12011-014-9925-7
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The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats.
Diabetes recently has reached almost epidemic levels worldwide. Diabetic cataract is one of the earliest secondary complications of diabetes, and it is characterized by opacification of the eye lens . Approximately 42 % of the world’s blindness can be attributed to diabetic cataracts . Diabetes-associated cataractogenesis is well known to be initiated by osmotic stress caused by the intralenticular accumulation of polyols produced by the polyol pathway [3, 4]. In diabetes, excess glucose enters the sorbitol pathway. The consequences of increased sorbitol pathway activity in the lens include intracellular sorbitol accumulation and resulting osmotic stress . A longer duration of diabetes and a higher level of hemoglobin A1c (HbA1c) have been reported to be significantly associated with a higher prevalence of diabetic cataracts [6, 7].
Very few drugs can directly prevent diabetic complications independent of the glucose levels. To prevent the development of diabetic complications, the different metabolic derangements occurring in diabetes need to be controlled. Many transition elements have been studied and found effective in controlling the altered glucose homeostasis in diabetes [8, 9]. Vanadium, element number 23, atomic weight 50.94, is normally present at very low concentrations (<10−8 M) in virtually all cells in plants and animals. As a potential therapeutic agent, it is attracting increasing attention. Vanadium compounds have the ability to imitate action of insulin [10, 11]. Oral administration of inorganic vanadium (IV, V) salts has shown an antidiabetic activity in patients . Preet  have reported that lower doses of vanadium administered in combination with Trigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses. So, the present study reports the efficacy of vanadium in delaying cataract in diabetic rat model.
Materials and Methods
Alloxan, analytical grade, was purchased from Sigma. Sodium vanadate (analytical grade) was purchased from Beijing Chemical Factory, China. Sodium vanadate (0.45, 0.9, and 1.8 g, respectively) was dissolved in 100 ml of normal saline. An ampule was filled with 0.4 ml of sodium vanadate (SV).
Wistar rats of either sex weighing 150–200 g were housed in polypropylene cages (six animals per cage) under controlled temperature (27 ± 2 °C) and in a natural light/dark cycle. They were fed with standard laboratory pellets. Food and water were provided ad libitum. The guidance suggestions for care of laboratory animals was followed according to the guidelines for caring for experimental animals published by the Ministry of Science and Technology of the People’s Republic of China. Care was taken to minimize discomfort, distress, and pain to the animals.
Healthy rats were made diabetic by intraperitoneal injection of alloxan (75 mg/kg). Serum glucose levels were measured 7 days after the injection, and animals showing hyperglycemia (the blood glucose level greater than 300 mg/dl) were selected as diabetic rats. They were randomly divided into various groups and treated orally with 4 ml of saline (alloxan), 0.45SV (0.05 mmol/kg body weight), 0.9SV (0.1 mmol/kg body weight), and 1.8SV (0.2 mmol/kg body weight), respectively. It was prepared each time before treatment. The other six normal rats were injected (iv) with the normal saline and used as the control group.
Measurement of Body Weight, Blood Glucose, and HbA1c
The body weights of the rats were measured on the 0th, 1st, 2nd, 3rd, and 4th weeks. On the 45th day, blood samples were collected from the orbital veins to measure the blood glucose and the HbA1c levels.
The intensity of cataract was scored once in a week for eight consecutive weeks. The cataract scores of ACO-treated groups were compared with normal group and diabetic control group. The cataract scores were determined using a slit lamp microscope. Progression and maturation of lenticular opacity was graded into five stages: stage 0, clear lenses and no vacuoles present; stage 1, vacuoles cover approximately one half of the surface of the anterior pole forming a subcapsular cataract; stage 2, some vacuoles have disappeared, and the cortex exhibits a hazy opacity; stage 3, a hazy cortex remains, and dense nuclear opacity is present; and stage 4, a mature cataract is observed as a dense opacity in both the cortex and nucleus. Opacity index was calculated to quantitatively evaluate the degree of lens opacity by the following formula:
Opacity index = (Number of eyes in each stage × Stage of the eye) / Total number of eyes.
Molecular Basis for the Delay of Cataract
At the end of 8 weeks, animals were sacrificed by CO2 asphyxiation, and lenses were dissected by posterior approach and stored at −70 °C until further analysis. Lens malondialdehyde (MDA), as thiobarbituric acid-reacting substances (TBARSs); protein carbonyl content; and activities of aldose reductase (AR) and sorbitol levels were determined according to the methods described previously . The specific activity of superoxide dismutase (SOD) was assayed according to the reported methods .
All data were analyzed by one-way analysis of variance, and the differences between means were established by Duncan’s multiple-range test. The data represents means and standard deviations. The significant level of 5 % (p < 0.05) was used as the minimum acceptable probability for the difference between the means.
Results and Discussion
Experimentally, alloxan cause a chronic diabetic condition that is characterized by high levels of blood glucose and insufficient levels of insulin. Prolonged exposure to chronic hyperglycemia can lead to the complication of diabetic cataracts . Alloxan-induced diabetic cataracts represent a dramatic accumulation of sorbitol in the lens, which results in the quick development of lens opacification . These models have been extensively used effectively to induce the diabetic complication of cataracts in various experimental animals to evaluate the therapeutic potential of drugs .
Effect of vanadium on blood glucose levels in alloxan-hyperglycemic rats
Blood glucose (mmol/l)
21.0 ± 2.0
18.9 ± 2.0
19.4 ± 3.0*
10.5 ± 2.0**
5.5 ± 1.5
Effect of vanadium on HbA1c levels in alloxan-induced hyperglycemic rats
Results of HbA1c
10.8 ± 0.20
9.7 ± 0.30
10.0 ± 0.26*
7.8 ± 0.28*
4.6 ± 0.20
Body weights of the diabetic group (p < 0.01) were significantly lowered at the end of the study. Vanadate (1.8SV) treatment was found to cause an increment in body weight gain (Fig. 1). The results of blood glucose from hyperglycemic rats induced by alloxan are presented in Table 1. The levels of blood glucose decreased after an administration of 1.8SV and 0.9SV (p < 0.01 and p < 0.05, respectively). It is consistent with the findings of other studies by Gil  and Shechter . The HbA1c which can be taken as a marker for the glycosylation of proteins was found to be significantly increased (p < 0.01) in diabetic rats. The different treatments (1.8SV and 0.9SV) given to the diabetic animals prevented the glycosylation of hemoglobin (Table 2).
Effect of vanadium on MDA, protein carbonyls, and SOD in rat lens
9.00 ± 2.37
7.09 ± 1.76
62.10 ± 4.30
8.49 ± 1.46
6.68 ± 1.76
60.00 ± 0.77
8.10 ± 0.66
6.22 ± 1.33
59.00 ± 0.33
7.50 ± 2.13
6.00 ± 1.66
55.01 ± 0.55
6.50 ± 2.10
5.88 ± 1.61
53.00 ± 0.55
Effect of vanadium on aldose reductase (AR) activity and sorbitol levels in rat lens
57.82 ± 2.20
2.811 ± 0.20
56.74 ± 5.30
2.223 ± 0.16
54.0 ± 6.26
2.108 ± 0.16
50.80 ± 2.28*
1.463 ± 0.14*
43.66 ± 5.20**
0.612 ± 0.20**
Our findings show that vanadium prevented the progression of existing cataracts. Although the cataracts did not disappear during the treatment period, agents that can prevent the progression of existing cataracts are useful for the treatment of this complication. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats.