Effects of zinc supplementation on serum levels of advanced glycation end products, matrix metalloproteinase 9 and caspase3 in patients with diabetic retinopathy

Abstract

Background and objective: Diabetes mellitus is one of the most important health problems in the world and Iran due to the spread of the disease, its complications, its mortality and related costs. One of the common complications of diabetes is diabetic retinopathy. Increased oxidative stress has been reported in diabetes and diabetic retinopathy patients. Besides, evidence linking oxidative stress to enhancement of advanced glycation end products (AGE), matrix metalloproteinase9 (MMP9) and caspase3. Considering the prevalence of zinc deficiency in diabetic patients and the ability of zinc to decrease oxidative stress, therefore, with the assumption of the effect of zinc on the modification of the AGEs, MMP9 and caspase3, the aim of this study was to investigate the effect of zinc on reducing of serum levels AGEs, MMP9 and caspase3 in patients with nonproliferative diabetic retinopathy. Method: In a randomized double-blind placebo-controlled clinical trial study, 36 patients with diabetic retinopathy and 18 healthy subjects (54 subjects in total) from 40 to 70 years have participated. Initially, serum levels of AGEs, MMP9 and caspase3 were compared between healthy subjects and patients with diabetic retinopathy. Patients with diabetic retinopathy were divided into two groups of zinc (N= 18) and placebo (N= 18). The zinc group received a 30 mg/day of zinc gluconate capsule and a placebo group received 30 mg/day dextrin maltose, for 1–2 hours after lunch for 3 months. During the intervention period, the type and dose of the drug were kept constant. Serum levels of AGEs and Precursors of its (including methylglyoxal (MGO), carboxymethyl lysine (CML), and pentosidine (PEN)), and MMP9 and caspase3 were measured by ELISA method and compared before and after the intervention. To assess dietary intake and physical activity of the subjects, 24-hour recall and international physical activity questionnaire were used respectively. Results: There was no significant difference in terms of height, weight, body mass index, physical activity and hip circumference between the two groups (P>0.05). But waist circumference (p = 0.001) and waist to hip ratio (p = 0.019) in diabetic retinopathy group were significantly higher than healthy subjects. There was no significant difference between patients with diabetic retinopathy and healthy subjects regarding the serum levels of AGEs (MGO, CML and PEN), MMP9 and Caspase3 (P>0.05). Zinc supplementation significantly increased the serum level of zinc in the Zn intake group (p <0.001). But zinc supplementation did not significantly alter the serum levels of AGEs (MGO, CML and PEN), MMP9, and Caspase3 in diabetic retinopathy patients (P>0.05). After examining the relationship between variables in patients with diabetic retinopathy before intervention, there was a positive significant correlation between Caspase3 and energy (r = 0.432, p = 0.009), protein (p = 0.004, r = 0.468, p) and fat (r = 0.486, p = 0.003) and Also, there was a positive and significant correlation between MGO and protein (r = 0.393, p = 0.018) Also, there was a significant correlation between serum levels of AGEs (MGO, CML and PEN), MMP9, and Caspase3 (p <0.001). Conclusion: In the present study, there was no significant difference in serum levels of AGEs, MMP9 and caspase3 between diabetic retinopathy and healthy subjects. Additionally, zinc also supplementation did not differ in serum levels of AGEs, MMP9 and caspase3 in diabetic retinopathy patients.