The effect of diabetes mellitus on active avoidance learning in rats: The role of nitric oxide

Growing data report memory and other cognitive problems among individuals with diabetes mellitus. Nitric oxide may play a key role in many physiological and pathological situations. The aim was to investigate the role of NO in diabetes-induced changes in learning and lipid peroxidation. Six groups of10 rats each were formed: control (C), diabetic (D), control+L-arginine (CA), diabetic+L-ar-ginine (DA), control+L-NAME (CN), and diabetic+L-NAME (DN) groups. Experimental diabetes mellitus was induced by injection of streptozotocin (60 mg/kg body weight). 160 mg/kg/day L-ar-ginine or 10 mg/kg/day L-NAME were injected intraperitoneally to the relevant groups for eight weeks. Active avoidance behavior was studied in the middle of the eighth week using an automated shuttle box. Brain and hippocampal nitrite levels were measured by a fluorometric method. TBARS levels were measured fluorometrically using 1,1,3,3-tetramethoxypropane as a standard. The active avoidance training indicated that diabetes was associated with learning impairment. Administration of L-NAME and L-arginine significantly impaired active avoidance performance compared with the control group. They also decreased glucose level in group DA compared with the diabetic group. Brain nitrite level was significantly different in the diabetic group; hippocampus nitrite level tended to be lower in the L-NAME groups than the diabetic and control groups, although L-arginine increased hippocampal and brain nitrite values in the CA group compared with control groups. Brain and hippocampal TBARS levels were significantly higher in diabetic than in control rats. Imbalance related to nitric oxide production may contribute to cognitive dysfunction in diabetes mellitus. © Med Sci Monit, 2009

The effect of chronic N(G)-nitro-L-arginine methyl ester (L-NAME) administration on visual evoked potentials and oxidative stress in streptozotocin induced diabetic rats

Objective: The aim of this study was to investigate the effects of N(G)-nitro-L-argininemetyl-ester (L-NAME) on visual evoked potentials (VEPs) and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Methods: Wistar rats were assigned to one of four groups: control (C), diabetic (D), control + L-NAME (CN) and diabetic + L-NAME (DN). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Three days after the STZ injection, diabetes was confirmed by measuring tail blood glucose concentration. L-NAME was injected intraperitoneally to the CN and DN groups at a dose of 10 mg/kg/d for eight weeks. VEPs were recorded by a photic stimulator. Thiobarbituric acid-reactive substance (TBARS) as an index of oxidative stress, and nitrite levels were measured fluorometrically in the brain and retina tissues. Results: L-NAME treatment produced a significant decrease in nitrite levels with respect to the control group, and body weight, water and food consumption and plasma glucose concentrations of the diabetic rats. TBARS concentrations were increased in diabetic rats. Although L-NAME treatment significantly increased the retina and brain TBARS levels in CN group, decreased TBARS concentrations were found in diabetic rats. All VEP components were significantly increased in diabetic rats. L-NAME caused a significant delay in all VEP components in CN group. Conclusion: Our results clearly showed that although L-NAME improved clinical manifestations of diabetes such as polyphagia, polydipsia, and also plasma glucose and TBARS concentrations in brain and retina tissues, it did not alter prolonged VEP latencies in diabetic state