الفهرس 
Diabetic nephropathyOnly 14 pages are availabe for public view
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Abstract
SUMMARY
Diabetes mellitus (DM) is a major global health problem; the number of individuals with diabetes is increasing dramatically worldwide. Diabetes mellitus is characterized by complications affecting several organs, including the kidney, in many countries diabetes has become the single most frequent cause of end-stage renal disease. It was recently found that oxidative stress which results from imbalance between ROS production and antioxidant defense mechanisms is involved in the pathogenesis of diabetic nephropathy, increased ROS production result in formation of cytokines and growth factors which participate in the pathogenesis of DN.
There is mounting evidence to support the notion that antioxidants can prevent, and even reverse, many early changes in the vascular and neurological tissues from diabetic animals.
This study was carried out in order to clarify the prophylactic effect of vitamin E supplementations on diabetic nephropathy in diabetic animals and the possible antioxidative protective action of the angiotensin receptor blocker.
This study was carried out on 5 main groups of adult male wistar albino rats. The first of them is the control group received no medications. The 2nd group was given a single intraperitoneal injection of STZ at a dose of 40 mg/kg which resulted in development of type 1 diabetes. The 3rd group diabetic group received losertan potassium at dose (1mg/kg), it was administrated once the rats became diabetic for 8 weeks. The 4th group diabetic group received vitamin E at a dose of (1 gm /kg), it was administrated once the rats became diabetic for 8 weeks. The 5th group received both vitamin E at a dose of (1 gm/kg) and losertan potassium at dose (1 mg/kg) orally. Both were administrated once the rats became diabetic for 8 weeks.
The parameters used to evaluate the metabolic consequences of diabetes were serum glucose, triglycerides and total cholesterol. The kidney function was evaluated by the serum creatinine and histopathological examination of the kidney using PAS stain. While the immunohistochemical examination of the glomerular Cu, Zn-SOD used to assess the oxidative stress in the kidney.
The obtained results of this study could be summarized as follow:
• The intraperitoneal injection of the rats with a single dose of STZ (40 mg/kg) resulted in diabetes mellitus manifested by a significant increase in the serum glucose level and also was associated with significant increase in the serum creatinine, serum triglycerides and serum total cholesterol. The examination of the glomeruli showed class II glomerulosclerosis and there was increase in the score of the glomerular Cu,Zn SOD which is used as a marker of the oxidative stress.
• On studying the prophylactic effect of losartan potassium by a dose (1mg/kg) on the kidney function, the rats were administrated the losartan once the diabetes was diagnosed for 8 weeks, there was a significant decrease in the serum glucose, serum creatinine, serum triglycerides and serum total cholesterol, while the glomeruli showed regression in the development of the glomerulsclerosis and also the score of the glomerular Cu,Zn SOD was decreased.
• On studying the prophylactic effect of vitamin E by a dose (1gm/kg) on the kidney function, the rats were administrated the vitamin E once the diabetes was diagnosed for 8 weeks, there was a significant decrease in the serum glucose, serum creatinine, serum triglycerides and serum total cholesterol, while the examination of the glomeruli showed more regression in the development of the glomerulsclerosis and also the score of the glomerular Cu,Zn SOD was decreased.
• On studying the prophylactic effect of both losartan potassium by a dose (1mg/kg) and vitamin E by a dose (1gm/kg) on the kidney function, the rats were administrated the losartan potassium and vitamin E once the diabetes was diagnosed for 8 weeks, there was a significant decrease in the serum glucose, serum creatinine, serum triglycerides and serum total cholesterol, while the examination of the glomeruli showed regression in the development of the glomerulsclerosis and also the score of the glomerular Cu,Zn SOD was decreased.
• By comparing the prophylactic effect of losartan potassium , vitamin E and both together there was non significant decrease in the serum glucose, serum creatinine and serum triglycerides, however there was a significant decrease in serum total cholesterol on using vitamin E alone or in combination with losartan rather than using the losartan alone indicating that the vitamin E has a better lowering effect on the total cholesterol, the examination of the glomeruli showed that the vitamin E alone or in combination with losartan led to more significant reduction in the glomerulosclerosis than the losartan did, but there was non- significant change in the score of Cu,Zn SOD between the three groups
from the above results we conclude that the pathogenesis of the diabetic nephropathy is mediated even partially through oxidative stress and that the losartan potassium and vitamin E have a renoprotective effect; however the vitamin E has more protective effect than the losartan and the combination of them had no additive effects.
RECOMMENDATIONS
• Further studies on the prophylactic effects of the antioxidants on the other diabetic complications such as diabetic retinopathy and diabetic neuropathy.
• Further studies on the antioxidants if they could have a possible curative effect in cases of diabetic nephropathy.