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The goal of this study was to investigate the effect of different phosphodiesterase inhibitors (PDEIs), on renal oxidant/antioxidant balance in diabetic rats. Our study was conducted on 125 rats, diabetes was induced in 100 rats by a single administration of streptozocin (STZ). Diabetic rats were divided into four equal groups. The first group was assigned as diabetic control, the remaining three groups were treated with pentoxifylline, sildenafil and milrinone via drinking water for 15 successive days, another group of 25 normal rats was assigned as non-diabetic control. Significant increase in plasma levels of glucose, urea, creatinine, malondialdehyde (MDA), and nitric oxide (NO) with a concomitant decrease in the levels of insulin, reduced glutathione (GSH), glutathione peroxidase (Gpx), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were observed in diabetic rats. These alterations were reverted back to near normal level after treatment with PDEIs. Our data seem to suggest a potential role of PDEIs in maintaining health in diabetes by reducing the progression of diabetic nephropathy.

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.

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.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.Plasma ghrelin values were significantly (P0.001) decreased in the MetS group versus control group. Arterial stiffness was noticed in MetS group by significantly (P0.01) increased IMT and baPWV (P0.001) matched with control group. Plasma ghrelin concentrations were negatively associated with age, smoking, FPG, HbA1c, CRP, TNF-alpha, baPWV, and Lt Carotid IMT.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.

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.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.Paricalcitol and combined treatment significantly (P0.01) reduced the level of fasting, postprandial blood glucose, homeostatic model assessment-insulin resistance, cardiac malondialdehyde and nitric oxide. Moreover, they significantly (P0.01) increased the levels of insulin and c-peptide compared to diabetic control rats. Combined treatment significantly (P0.01) raised the level of glutathione, glutathione S-transferase and catalase more than monotherapy.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.