Effects of curcumin on retinal oxidative stress and inflammation in diabetes

Renu A Kowluru, Mamta Kanwar, Renu A Kowluru, Mamta Kanwar

Abstract

Background: Oxidative stress and inflammation are implicated in the pathogenesis of retinopathy in diabetes. The aim of this study is to examine the effect of curcumin, a polyphenol with antioxidant and anti-inflammatory properties, on diabetes-induced oxidative stress and inflammation in the retina of rats.

Methods: A group of streptozotocin-induced diabetic rats received powdered diet supplemented with 0.05% curcumin (w/w), and another group received diet without curcumin. The diets were initiated soon after induction of diabetes, and the rats were sacrificed 6 weeks after induction of diabetes. The retina was used to quantify oxidative stress and pro-inflammatory markers.

Results: Antioxidant capacity and the levels of intracellular antioxidant, GSH (reduced form of glutathione) levels were decreased by about 30-35%, and oxidatively modified DNA (8-OHdG) and nitrotyrosine were increased by 60-70% in the retina of diabetic rats. The levels of interleukin-1beta (IL-1beta) and vascular endothelial growth factor (VEGF) were elevated by 30% and 110% respectively, and the nuclear transcription factor (NF-kB) was activated by 2 fold. Curcumin administration prevented diabetes-induced decrease in the antioxidant capacity, and increase in 8-OHdG and nitrotyrosine; however, it had only partial beneficial effect on retinal GSH. Curcumin also inhibited diabetes-induced elevation in the levels of IL-1beta, VEGF and NF-kB. The effects of curcumin were achieved without amelioration of the severity of hyperglycemia.

Conclusion: Thus, the beneficial effects of curcumin on the metabolic abnormalities postulated to be important in the development of diabetic retinopathy suggest that curcumin could have potential benefits in inhibiting the development of retinopathy in diabetic patients.

Figures

Figure 1
Figure 1
Structure of curcumin. 1,7-bis (4-hydroxy-3-methoxy-phenyl) hepta-1, 6-diene-3, 5-dione).
Figure 2
Figure 2
Effect of curcumin on diabetes-induced oxidative stress in the retina. (a) Total antioxidant capacity of the retina was quantified by measuring the ability of the retina to inhibit oxidation of ABTS by metmyoglobin using 5–10 μg retina protein. (b) Retinal GSH was estimated in the deproteinizing retinal homogenate using a kit from Cayman Chemical (MI). Each sample was measured in duplicate, and the values are represented as mean ± SD of 7–8 rats in diabetes group and 7–9 rats each on normal and diabetes + curcumin groups. Norm = normal; Diab = Diabetes; Diab + Curc = Diabetes + curcumin treated rats. *P < 0.05 compared to normal, #P < compared to diabetes + curcumin.
Figure 3
Figure 3
Effect of curcumin on oxidatively modified DNA levels in the retina. 8-OHdG levels were measured in the retina using an ELISA kit from Oxis Research. Values are represented as mean ± SD of 6–8 rats in each group. *P < 0.05 compared to normal, and #P < 0.05 compared to diabetes + curcumin.
Figure 4
Figure 4
Effect of curcumin on retinal nitrotyrosine levels in diabetes. Nitrotyrosine-EIA kit was used to quantify nitrotyrosine in the retina. Each sample was measured in duplicate. The figure represents mean ± SD of 6 rats each in normal and diabetes + curcumin groups and 7 rats in diabetes group. *P < 0.05 compared to normal, #P < compared to diabetes + curcumin.
Figure 5
Figure 5
Effect of curcumin on diabetes-induced increase in retinal IL-1β levels. An ELISA kit from R&D Systems, Minneapolis, MN, was used to quantify IL-1β in the retina. Each sample was run in duplicate to ensure reproducibility of the data. IL-1β values (pg IL-1β/mg protein) are mean ± SD obtained from 8 rats each in diabetes and diabetes + curcumin groups and 6 rats in normal group. *P < 0.05 and #P < 0.05 compared to normal and diabetes + curcumin groups respectively.
Figure 6
Figure 6
Effect of curcumin on NF-kB activation. NF-kB activation was determined in the retinal homogenate by ELISA method (kit from Active Motif.) using antibody specific for p65 subunit of NF-kB. Secondary antibody conjugated to horseradish peroxidase was used to quantify the activated form spectrophotometrically. The figure represents mean ± SD of 5–6 rats each in of the 3 groups. *P < 0.05 compared with normal or diabetes + curcumin groups.
Figure 7
Figure 7
VEGF levels in curcumin-treated rats. VEGF concentrations were measured in the retina of rats in normal, diabetes and diabetes + curcumin groups using an ELISA kit from R&D Systems. Results are presented as mean ± SD of 6 rats in diabetes and 7 rats each in normal and diabetes + curcumin groups. *P < 0.05 compared to normal, and #P < 0.05 compared to diabetes + curcumin.

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