Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats

Abstract

Purpose To evaluate the role of melatonin, an antioxidant agent, in diabetic oxidative stress and vascular damage. Methods Diabetes was induced in 21 male Wistar rats by intraperitoneal (IP) administration of streptozotocin and then the rats were equally and randomly allocated to diabetic, melatonin, and vehicle groups. Seven healthy normal rats with similar features comprised the control group as the fourth group. All animals were followed for 12 weeks. The melatonin group received IP melatonin daily and the vehicle group received 2.5% ethanol IP at the last month. At the end of 12 weeks, the rats were killed and retinas were harvested. The retinas were investigated for the existence of hypoxiainducible factor 1-a (HIF-1a), vascular endothelial growth factor A (VEGF-A), and pigment epithelium-derived factor (PEDF) by ELISA. Retinal oxidative stress is quantitated by measuring nitrotyrosine and malondialdehyde levels. Retinal immunohistochemistry with antibody against CD31 antigen was carried out on retinal cross-sections. For statistics, ANOVA test was used for multiple comparisons. Results Hyperglycemia increased retinal oxidation as measured through levels of nitrotyrosine and malondialdehyde. Diabetic retinas are also associated with abnormal vascular changes such as dilatation and deformation. HIF-1a, VEGF-A, and PEDF were all increased because of diabetic injury. Melatonin showed a potential beneficial effect on retinopathy in diabetic rats. It decreased retinal nitrotyrosine and malondialdehyde levels, showing an antioxidative support. The vasculomodulator cytokines are decreased accordingly by melatonin therapy. Melatonin normalized retinal vascular changes as well. ConclusionMelatonin may show some advantage on diabetic vascular changes through decreasing oxidative stress and vessel-related cytokines.

Melatonin Attenuates Aortic Endothelial Permeability and Arteriosclerosis in Streptozotocin-Induced Diabetic Rats

“…The dose of melatonin used (10 mg/kg/d) was selected based on previous studies. 36,37 Our results demonstrated that melatonin ameliorated lipid metabolism, hemodynamic and endothelial dysfunctions, and vascular hyperpermeability to a various extent in diabetic rats. Most importantly, our study is the first to show that the suppression of MLCK-and p-MYPT-mediated p-MLC expression, which was partly associated with the ERK/ p38 signal transduction pathway for the alleviation of hyperpermeability in both hyperglycemic and hypercholesterolemic states, played a crucial role in the protective effects of melatonin.…”

Ebola virus disease: potential use of melatonin as a treatment

“…These are, but not limited to, the fact that melatonin suppresses the levels of TNF-a, IFN-a, IL6, IL8, TF, MCP-1, VEGF, phosphorylation of JNK, and the degradation of the tight junctional proteins and it reduces endothelial apoptosis [13][14][15] Protecting against endothelial cell injury and preserving vascular structure and function are important to avoid the deadly hemorrhage in late stage EVD.…”

The role and therapeutic potential of melatonin in age‐related ocular diseases

“…In this sense, melatonin can modulate sirtuins expression/activity and can induce autophagy via mTOR‐dependent pathway (Figure ) . Furthermore, some of the sirtuins effects described above have also been reported for melatonin . Indeed, melatonin treatment of diabetic rats inhibits their MMP‐9 expression and VEGF secretion (Figure ) .…”

“…Certainly, melatonin offers protection from oxidative stress and increases the viability of retinal cells involved in diabetic retinopathy including RPE, photoreceptors, retinal ganglion cells, and Müller cells (Figure ) . Furthermore, melatonin prevents the nitro‐oxidative stress of diabetic retina and high glucose‐induced inflammatory response of RPE as well as retinal endothelial cells (Figure )…”