الفهرس 
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Abstract
The present study aimed to investigate the effect of vitamin E, atorvastatin and their combination on nephrotoxicity resulting from administration of potassium dichromate in rats.
Potassium dichromate-induced nephrotoxicity:
The rats were randomly classified into 5 groups of eight animals each: The first group received vehicle and served as normal control group; the second group was subjected to a single s.c injection of potassium dichromate (15mg/kg) on day 14. The third group was pretreated with vitamin E (200mg/kg) for 14 days before s.c. injection of potassium dichromate and continued for 2 more days. The fourth group was pretreated with atorvastatin (10mg/kg) for 14 days before s.c. injection of potassium dichromate and continued for 2 more days. The fifth group was pretreated with the combination of vitamin E (200mg/kg) and atorvastatin (10mg/kg) for 14 days before s.c. injection of potassium dichromate and continued for 2 more days.
The renoprotective potential of the chosen agents was evaluated based on:
1. Renal function tests: including serum levels of creatinine, urea and albumin.
2. Electrolyte levels: including serum levels of sodium and potassium.
3. Oxidative stress biomarkers including kidney superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), total nitrate/nitrite (NOx) contents.
4. Lipid profile: including total cholesterol (Total-C), low density lipoprotein- cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C).
5. Inflammatory biomarkers as kidney myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-) content.
6. Metallothionein content (MT) and histopathological examination of kidney tissue.
Results of the present study can be summarized as follows:
I- Administration of a single dose of potassium dichromate caused:
1) Nephrotoxicity characterized by significant increase in both serum creatinine and urea levels.
2) There was a significant decrease in renal GSH content, MT content, and SOD activity.
3) There was a significant increase in renal MDA content, NOx content, TNF-α content and MPO activity.
4) There was a significant increase in serum T-Ch, LDL-C and HDL-C.
5) Histopathological examination of the kidney showed degeneration of most of the convoluted tubules, congestion of glomerular tuft and haemorrhage.
II- Effect of test agents on potassium dichromate-induced nephrotoxicity:
Effect of pretreatment with vitamin E on potassium dichromate-induced nephrotoxicity:
1) Vitamin E improved kidney function tests manifested by a significant decrease in both serum creatinine and urea levels. This was relevant to an improvement in the renal histopathological features.
2) Vitamin E caused significant reduction in renal MDA content coupled by a significant increase in renal SOD activity.
3) Vitamin E caused a significant decrease in renal NOx content and TNF- content.
4) Vitamin E showed anti-inflammatory and antioxidant activities as evidenced by reduced oxidative stress as well as inflammatory biomarkers.
III- Effect of pretreatment with atorvastatin on potassium dichromate-induced nephrotoxicity:
1) Atorvastatin improved kidney function tests as evident by a significant decrease in both serum creatinine and urea levels. This was relevant to an improvement in the renal histopathological features.
2) Atorvastatin caused a significant reduction in renal MDA content and did not restore renal SOD activity.
3) Atorvastatin caused a significant decrease in renal NOx content, TNF-α content and MPO activity.
4) Atorvastatin showed anti-inflammatory and antioxidant activities as evidenced by reduced oxidative stress as well as inflammatory biomarkers.
IV- Effect of pretreatment with atorvastatin, along with vitamin E on potassium dichromate-induced nephrotoxicity:
1) Co-administration of atorvastatin and vitamin E improved kidney function tests manifested by a significant decrease in both serum creatinine and urea
levels. However, histopathological examination revealed minimal improvement.
2) Co-administration of atorvastatin and vitamin E caused not only a significant reduction in renal MDA content but also normalized it. However renal SOD was not restored, although pretreatment with vitamin E separately restored renal SOD activity.
3) Co-administration of atorvastatin and vitamin E caused a significant decrease in renal NOx content, TNF-α content and MPO activity.
4) Co-administration of atorvastatin and vitamin E showed anti-inflammatory and antioxidant activities as evidenced by reduced oxidative stress as well as inflammatory biomarkers.
Conclusions
Depending on the results of the present study it could be concluded that:
1) Potassium dichromate caused marked nephrotoxicity associated with oxidative stress.
2) Both vitamin E and atorvastatin improved the renal function tests and showed anti-inflammatory and antioxidant activities as evidenced by reduced oxidative stress as well as inflammatory biomarkers.
3) Both vitamin E and atorvastatin protected against potassium dichromate insult.
4) However the co-administration of vitamin E with atorvastatin did not offer any further protection against potassium dichromate toxicity than the protection offered by each drug alone.
5) Further preliminary clinical studies are needed to verify the nephroprotective effects of atorvastatin and vitamin E before clinical application.