Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

Abstract

Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-α, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury.

The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats

“…Studies have shown that carvedilol has markedly improved cardiac performance and reduced mortality in humans [21,22]. Morsy et al [9] reported that carvedilol can protect STZ-induced early diabetic nephropathy in rats via antioxidant as well as anti-inflammatory activities.…”

“…The diabetic rats were treated with carvedilol (10 mg/kg/day p.o. [9]; Roche, Indianapolis, IN, USA) or vehicle for 16 weeks. All the rats were provided with water and food ad libitum.…”

“…Studies have manifested that carvedilol has vasodilatation, antioxidative stress and anti-inflammation effects [6,7,8]. Moreover, carvedilol protects against streptozotocin (STZ)-induced early diabetic nephropathy in rats via anti-inflammation and oxidation [9]. …”

Anti‐oxidative effect of the β‐blocker carvedilol on diabetic nephropathy in non‐obese type 2 diabetic rats

“…It has been reported that carvedilol ameliorates renal dysfunction even in streptozotocin‐diabetic animals with a concomitant reduction in oxidative stress . In these studies, thiobarbituric acid‐reactive substances, malondialdehyde, glutathione and the nitrite/nitrate ratio were evaluated as markers of oxidative stress.…”

Beta-adrenoblockers of third generation as medicines for drug therapy of patients with chronic kidney disease

“…Од-новременно у крыс с СД по сравнению с нелечены-ми животными снижается уровень сывороточного креатинина, возрастает почти в 3 раза клиренс креа-тинина и более чем в 2 раза снижается отношение альбумин/креатинин мочи. По данным электронной микроскопии карведилол практически полностью восстанавливает к этому времени толщину гломеру-лярной базальной мембраны и препятствует отщеп-лению ножек подоцитов, сохраняя их морфологиче-скую структуру [26].…”