Protective effect of cinnamon on diabetic cardiomyopathy in nicotinamide-streptozotocin induced diabetic rat model.

There is an increase in the incidence and prevalence of type-2 diabetes and obesity which leads to the structural and functional changes in myocardium leading to a lethal complication called diabetic cardiomyopathy (DCM). In the present study, we investigated the preventive effect of cinnamon (3% of Cinnamomum zeylanicum bark powder in AIN-93 diet for 3 months) feeding on DCM and the concerned mechanisms in a rodent model. Experimental diabetes was induced by a single intraperitoneal injection of 40 mg/kg b.w streptozotocin (STZ), 15 min after the ip administration of 60 mg/kg b.w of nicotinamide (NA) in Wistar-NIN (WNIN) male rats. The oxidative stress parameters were investigated by assessing superoxide dismutase (SOD), glutathione-s-transferase (GST) enzyme activity, protein carbonyls and malondialdehyde (MDA) levels. The histopathology of myocardium was analyzed by H&E and Masson's trichrome staining, and scanning electron microscopy. The changes in diabetic rat heart involved the altered left ventricular parietal pericardium, structural changes in myocardial cells, enhanced oxidative stress. Masson's trichrome and H&E staining have shown increased fibrosis, and perinuclear vacuolization in NA-STZ induced diabetic rat myocardium. Cinnamon feeding prevented the oxidative stress and myocardial alterations in the heart of diabetic rats. Taken together, these results suggest that cinnamon can effectively prevent the metabolic and structural changes in NA-STZ induced diabetic cardiomyopathy.

Impact of obesity with impaired glucose tolerance on retinal degeneration in a rat model of metabolic syndrome.

PURPOSE: Metabolic syndrome (MetS) is associated with several degenerative diseases, including retinal degeneration. Previously, we reported on progressive retinal degeneration in a spontaneous obese rat (WNIN/Ob) model. In this study, we investigated the additional effect of impaired glucose tolerance (IGT), an essential component of MetS, on retinal degeneration using the WNIN/GR-Ob rat model. METHODS: The retinal morphology and ultrastructure of WNIN/GR-Ob and age-matched littermate lean rats were studied by microscopy and immunohistochemistry. The retinal transcriptome of WNIN/GR-Ob was compared with the respective lean controls and with the WNIN/Ob model using microarray analysis. Expression of selected retinal marker genes was studied via real-time PCR. RESULTS: Progressive loss of photoreceptor cells was observed in WNIN/GR-Ob rats with an onset as early as 3 months. Similarly, thinning of the inner nuclear layer was observed from 6 months in these rats. Immunohistochemical analysis showed decreased levels of rhodopsin and postsynaptic density protein-95 (PSD-95) proteins and increased levels of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and calretinin in WNIN/GR-Ob rats compared with the age-matched lean controls, further supporting cellular stress/damage and retinal degeneration. The retinal transcriptome analysis indicated altered expression profiles in both the WNIN/GR-Ob and WNIN/Ob rat models compared to their respective lean controls; these pathways are associated with activation of pathways like cellular oxidative stress response, inflammation, apoptosis, and phototransduction, although the changes were more prominent in WNIN/GR-Ob than in WNIN/Ob animals. CONCLUSIONS: WNIN/GR-Ob rats with added glucose intolerance developed retinal degeneration similar to the parent line WNIN/Ob. The severity of retinal degeneration was greater in WNIN/GR-Ob rats compared to WNIN/Ob, suggesting a possible role for IGT in this model. Hence, the WNIN/GR-Ob model could be a valuable tool for investigating the impact of MetS on retinal degeneration pathology.

Effect of chronic hyperglycemia on crystallin levels in rat lens.

Crystallins are the major structural proteins in the vertebrate eye lens that contribute to lens transparency. Although cataract, including diabetic cataract, is thought to be a result of the accumulation of crystallins with various modifications, the effect of hyperglycemia on status of crystallin levels has not been investigated. This study evaluated the effect of chronic hyperglycemia on crystallin levels in diabetic cataractous rat lens. Diabetes was induced in rats by injecting streptozotocin and maintained on hyperglycemia for a period of 10weeks. At the end, levels of α-, ß-, γ-crystallins and phosphoforms of αB-crystallins (αBC) were analyzed by immunoblotting. Further, solubility of crystallins and phosphoforms of αBC was analyzed by detergent soluble assay. Chronic diabetes significantly decreased the protein levels of α-, ß- and αA-crystallins (αAC) in both soluble and insoluble fraction of lens. Whereas γ-crystallin levels were decreased and αBC levels were increased in lens soluble fraction with no change in insoluble fraction in diabetic rat lens. Although, diabetes activated the p38MAPK signaling cascade by increasing the p-p38MAPK in lens, the phosphoforms of αBC were decreased in soluble fraction with a concomitant increase in insoluble fraction of diabetic lens when compared to the controls. Moreover, diabetes strongly enhances the degradation of crystallinsand phosphoforms of αBC in lens. Taken together, the decreased levels of crystallins and insolubilization of phosphoforms of αBC under chronic hyperglycemia could be one of the underlying factors in the development of diabetic cataract.