Abstract
Background Increased activity of aldose reductase (AR) is one of the mechanisms involved in the development of diabetic complications. Inhibiting AR can be a target to prevent diabetes complications. This study is aimed at evaluating the effect of cyclohexane (CH) and ethanol extracts (ET) of walnut leaves on AR activity in the lens and testis of diabetic rats. Methods Fifty-six male rats classified into seven groups as control and treatment groups and treated for 30 days. The treatment groups were treated with different concentrations of ET and CH. The diabetic control (DC) group was exposed to streptozotocin. AR activity was measured in the lens and testis. The expression of AR in the testis was evaluated by the immunohistochemistry method. Results Both extracts significantly reduced the AR activity (ng/mg of tissue protein) in the testis (0.034 ± 0.004, 0.038 ± 0.010, and 0.040 ± 0.007 in the treatment groups vs. 0.075 ± 0.007 in the DC group) and lens (1.66 ± 0.09, 2.70 ± 0.47, and 1.77 ± 0.20 in the treatment groups vs. 6.29 ± 0.48 in the DC group) of the treatment group compared to those of the DC group (P < 0.05). AR expression in the testes of the treatment groups was decreased compared with that of the DC group (P < 0.0001). Conclusion Walnut leaf extracts can reduce the activity and localization of AR in the testes and its activity in the lens of diabetic rats.
Highlights
Increased activity of aldose reductase (AR) is one of the mechanisms involved in the development of diabetic complications
Male reproductive dysfunction and cataract are important complications of diabetes mellitus [2]. The development of these complications was suggested to be through increasing the activity of aldose reductase (AR) in the polyol pathway (PPW), advanced glycation end products (AGEs), overexpression of AGE receptor, protein kinase C isoform activation, glucosamine pathway activation, and excessive oxidative stress
Aldose reductase activity in the testis of the diabetic control group was significantly higher than that of the other groups, and treatment with cyclohexane or ethanol extracts decreased its activity significantly compared to the diabetic control groups (compared to treatment 1 (P = 0:0004), treatment 2 (P = 0:0032), and treatment 3 (P = 0:0026)) (Figures 1 and 2)
Summary
Increased activity of aldose reductase (AR) is one of the mechanisms involved in the development of diabetic complications. Male reproductive dysfunction and cataract are important complications of diabetes mellitus [2] The development of these complications was suggested to be through increasing the activity of aldose reductase (AR) in the polyol pathway (PPW), advanced glycation end products (AGEs), overexpression of AGE receptor, protein kinase C isoform activation, glucosamine pathway activation, and excessive oxidative stress. These conditions can cause important complications such as neuropathy, nephropathy, retinopathy, and cataracts [3]. Increased oxidative stress after hyperglycemia is caused mainly through autoxidation glycosylation, AGE formation, and increasing polyol pathway activity [5]
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