The counteracting effects of (-)-Epigallocatechin-3-Gallate on the immobilization stress-induced adverse reactions in rat pancreas.

Many studies suggest that Epigallocatechin-3-Gallate (EGCG) has many protective effects. But little is known about its protective effects against chronic restraint stress-induced damage in rats. The aim was to demonstrate the potential protective effects of EGCG against harmful pancreatic damage to the immobilization stress in the rat model. Forty rats, 2 months old, were divided into four groups (n = 10): control group; EGCG group, rats received EGCG by gavage (100 mg/kg /day) for 30 days; stressed group, rats exposed to immobilization stress; and stressed with EGCG group, rats exposed to immobilization stress and received EGCG for 30 days. Glycemic status parameters, corticosterone, and inflammatory markers were investigated on the first day, 15th day, and the 30th day of the experiment. Pancreatic oxidative stress markers and cytokines were evaluated. Histological, immunohistological, and statistical studies were performed. On the 15th day, fasting blood glucose (FBG), fasting plasma insulin (FPI), homeostatic model assessment for insulin resistance (HOMA-IR), and fasting plasma corticosterone were significantly higher in the stressed group when compared with first and 30th day in the same group as well as when compared with control and stressed with EGCG groups. The stressed group revealed significantly higher pancreatic IL-1ß, IL-6, TNF-α, MDA, and NO, serum amylase and serum lipase, and significantly lower GSH, SOD, and CAT when compared to control and stressed with EGCG groups. EGCG treatment attenuated the pancreatic stress-induced cellular degeneration, leucocytic infiltration, and cytoplasmic vacuolations; significantly decreased area percentage of collagen fibers; and significantly increased mean area percentage of insulin immunopositive cell as compared with stressed group. EGCG is a protective agent against immobilization stress because of its anti-diabetic, anti-inflammatory, and and anti-oxidative stress properties, as confirmed by biochemical and histological alterations.

Beneficial effects of (-)-epigallocatechin-3-O-gallate on diabetic peripheral neuropathy in the rat model.

Diabetic neuropathic pain is characterized by spontaneous pain with hyperalgesia and allodynia. We investigated whether (-)-epigallocatechin-3-O-gallate could improve diabetic neuropathic pain development through hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. Diabetes was induced in rats by streptozotocin (55 mg/kg/once) and treated with (-)-epigallocatechin-3-O-gallate (25 mg/kg/orally/once/daily/5 weeks). Diabetic rats showed an increase in serum levels of glucose, nitric oxide, triglyceride, total cholesterol, and low-density lipoprotein-cholesterol with a decrease in high-density lipoprotein-cholesterol and body weight. Also, there was an elevation in brain malondialdehyde with a marked reduction in brain levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase. Furthermore, diabetic rats showed a clear reduction in plasma levels of insulin and an increase in plasma cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, diabetic rats exhibited hyperalgesia as indicated by a hot plate, tail immersion, formalin, and carrageenan-induced edema tests as well as brain histopathological changes (neuron degeneration, gliosis, astrocytosis, congestion and hemorrhage). (-)-Epigallocatechin-3-O-gallate treatment ameliorated alterations in body weight, biochemical parameters, pain sensation, and histopathological changes in brain tissue. (-)-Epigallocatechin-3-O-gallate offers promising hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory effects, which can prevent the development and progression of diabetic neuropathic pain.

The Potential Protective Effects of Diosmin on Streptozotocin-Induced Diabetic Cardiomyopathy in Rats.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a nonischemic myocardial disorder characterized by metabolic disturbances and oxidative stress in diabetic patients. The present paper aims to determine the protective effect of the phlebotrophic drug, diosmin, on DCM in a model of high-fat diet-fed and streptozotocin-induced type 2 diabetes in the rat. MATERIALS AND METHODS: The animals were divided into 4 groups (8 rats/group) as follows: vehicle-treated nondiabetic control group, vehicle-treated diabetic group, diosmin (50 mg/kg)-treated diabetic group and diosmin (100 mg/kg)-treated diabetic group. Treatment was given once daily orally by gavage for 6 weeks. Oxidant and antioxidant stress markers, inflammatory markers and proapoptotic and antiapoptotic gene expression using quantified real-time polymerase chain reaction were investigated. RESULTS: Diosmin treatment in diabetic rats lowered elevated blood glucose levels, homeostatic model assessment for insulin resistance, cardiac creatine kinase and lactate dehydrogenase enzymes, cardiac malondialdehyde and nitric oxide. Moreover, diosmin increased plasma insulin and c-peptide levels, cardiac glutathione content, superoxide dismutase, catalase and glutathione S-transferase activities. Also, diosmin treatment significantly (P < 0.05) lowered the levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), down-regulated cardiac Bcl-2-associated X protein and caspase 3 and 9 and up-regulated B-cell lymphoma 2 mRNA expression levels. CONCLUSIONS: Diosmin may have a sizeable therapeutic potential in the treatment of DCM due to antidiabetic, antioxidative stress, anti-inflammatory and antiapoptotic effects. Detailed studies are needed to disclose the precise mechanisms motivating the protective effect of diosmin .

The association between fetuin-A and testosterone levels and markers of arterial stiffness in Saudi subjects with type 2 diabetes mellitus.

BACKGROUND: Inconsistent results have been described regarding the part of fetuin-A and testosterone in arterial stiffness in type 2 diabetes mellitus (T2DM). AIM: To look into the links of serum fetuin-A and testosterone levels with brachial-Ankle pulse wave velocity (baPWV), a marker of arteriosclerosis and common carotid intima media thickness (ccIMT), a marker of early atherosclerosis, in diabetic Saudi men patients. SUBJECTS AND METHODS: One hundred and fifty adult male patients with T2DM and 60 non-diabetic control subjects were enrolled from different Saudi Arabia Taif hospitals. Biochemical analysis, anthropometric measurements, blood pressure, baPWV and ccIMT were investigated. RESULTS: Stepwise regression in diabetic patients revealed that the most important predictor of ba-PWV was serum fetuin-A followed by serum glucose and the most important predictor of ccIMT was serum fetuin-A followed by serum HDL then serum triglycerides. CONCLUSIONS: Only fetuin-A levels not testosterone are negatively associated with early markers of atherosclerosis.

The association between ghrelin levels and markers of arterial stiffness and inflammatory markers in Saudi subjects with metabolic syndrome.

BACKGROUND: Arterial stiffness is a principal cardiovascular risk factor. Metabolic syndrome (MetS) is a predisposing factor to arterial stiffness and persistent MetS circumstances can deteriorate the arterial stiffness severity. Low concentrations of plasma ghrelin are meticulously connected to arterial stiffness. This work targeted to judge the relationship between plasma ghrelin levels and intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) as markers of arterial stiffness and inflammatory markers and in Saudi subjects with MetS. PATIENTS AND METHODS: Eighty-four young adults were recruited from the visitors of the outpatient clinics of Taif hospitals, and then they were divided into a control group that involves subjects without MetS and a study group involving those with MetS. Anthropometric measurements, blood pressure, plasma ghrelin levels, fasting plasma glucose levels (FPG) and lipid profile were assessed. baPWV was measured by a volume plethysmograph while IMT was evaluated by ultrasonography. RESULTS: Plasma ghrelin values were significantly (P<0.001) decreased in the MetS group versus control group. Arterial stiffness was noticed in MetS group by significantly (P<0.01) increased IMT and baPWV (P<0.001) matched with control group. Plasma ghrelin concentrations were negatively associated with age, smoking, FPG, HbA1c, CRP, TNF-alpha, baPWV, and Lt Carotid IMT. CONCLUSIONS: Depending on our outcomes showing the valuable properties of ghrelin in the cardiovascular system in patients with metabolic syndrome, it can be postulated that ghrelin may be associated with markers of atherosclerosis.

Effect of Combination of Angiotensin-Converting Enzyme Inhibitors and Vitamin D Receptor Activators on Cardiac Oxidative Stress in Diabetic Rats.

BACKGROUND: The principle mediator of diabetic myocardial injury is oxidative stress. The aim was to compare the effect of monotherapy with enalapril, angiotensin-converting enzyme inhibitor and paricalcitol (vitamin D receptor activator), to the combined therapy with both drugs on the cardiac oxidant-antioxidant balance in the type 2 diabetic rats. MATERIALS AND METHODS: A total of 50 male Sprague-Dawley rats were divided into 5 groups, namely the normal control and diabetic, vehicle, enalapril, paricalcitol and paricalcitol and enalapril-treated groups. Enalapril was given at a dose of (25mg/L) in drinking water once daily and paricalcitol was given intraperitoneally (0.8µg/kg/3 × week) for 3 months. Glycemic status, cardiac oxidant-antioxidant parameters and histologic examination were determined. RESULTS: Paricalcitol and combined treatment significantly (P < 0.01) reduced the level of fasting, postprandial blood glucose, homeostatic model assessment-insulin resistance, cardiac malondialdehyde and nitric oxide. Moreover, they significantly (P < 0.01) increased the levels of insulin and c-peptide compared to diabetic control rats. Combined treatment significantly (P < 0.01) raised the level of glutathione, glutathione S-transferase and catalase more than monotherapy. CONCLUSION: The combination of angiotensin-converting enzyme inhibitors and vitamin D receptor activators has a superior effect on reducing cardiac oxidative stress by raising antioxidant activity than monotherapy in diabetic rats.