thiobarbituric-acid and Proteinuria

We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30 mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55 mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed. Diabetic rats after 8 weeks of STZ-administration developed apparent nephropathy by elevating serum creatinine, blood urea nitrogen and microproteinuria, and inducing glomerular-capsular wall distortion, mesangial expansion and tubular damage and renal oxidative stress. Fenofibrate (30 mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30 mg/kg/day p.o., 4 weeks) post-treatment (8 weeks after STZ-administration) was less-effective. However, both pre-and post fenofibrate treatments were effective in preventing diabetes-induced renal oxidative stress and lipid alteration in diabetic rats though the pretreatment was slightly more effective. Conversely, both pre-and post fenofibrate treatments did not alter elevated glucose levels in diabetic rats. It may be concluded that diabetes-induced oxidative stress and lipid alteration, in addition to a marked glucose elevation, play a detrimental role in the onset of nephropathy in diabetic rats. The pretreatment with low-dose fenofibrate might be a potential therapeutic approach in preventing the onset of nephropathy in diabetic subjects under the risk of renal disease induction. However, low-dose fenofibrate treatment might not be effective in treating the established nephropathy in diabetic subjects.

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Body Weight; Creatinine; Diabetic Nephropathies; Dose-Response Relationship, Drug; Female; Fenofibrate; Glutathione; Kidney; Lipids; Male; Organ Size; Proteinuria; Rats; Rats, Wistar; Thiobarbiturates; Time Factors

Exercise-induced proteinuria is a common consequence of physical activity, although its mechanism is not clear. We investigated whether free radicals generated during exercise play a role in post-exercise proteinuria in sedentary and treadmill-running trained rats, separately. Sedentary and trained rats were randomly divided into four sub-groups: control, antioxidant treatment, exhaustive exercise and an exhaustive exercise plus antioxidant treatment group. Antioxidant therapy was applied by intragastric catheter for 4 weeks with vitamin C (ascorbic acid, 50 mg x kg(-1) x day(-1)) and vitamin E (alpha-tocopherol, 20 mg x kg(-1).day(-1)). Twenty-four-hour urine samples were used for measuring protein levels and protein electrophoresis. Thiobarbituric acid (TBARS) and glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were assayed in blood and tissues. Increased urinary protein levels and mixed type proteinuria in electrophoresis were identified after exhaustive exercise in sedentary rats. Erythrocyte, kidney and muscle TBARS levels were significantly elevated in this group. Antioxidant treatment prevented the increase in urinary protein levels, TBARS levels and the occurrence of mixed type proteinuria after exhaustive exercise in sedentary rats. Exhaustive exercise in trained rats resulted in elevation of urine protein levels and mixed type proteinuria although kidney TBARS levels were not changed compared to those of the trained controls. Antioxidant therapy in trained and exhausted-trained animals resulted in decreased TBARS levels in the kidney but it did not affect urinary-increased protein levels or electrophoresis in exhausted animals. This findings suggest that the exercise-induced oxidant stress may contribute to post-exercise proteinuria in sedentary rats. However, this mechanism may not be responsible for proteinuria in trained rats.

Topics: Animals; Antioxidants; Glutathione; Male; Physical Conditioning, Animal; Proteinuria; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Thiobarbiturates