الفهرس 
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Abstract
The present study investigated the possible nephro protective effect of vitamin E, rosuvastatin or their combination against amikacin-induced nephrotoxicity in rats. The selected doses of the test drugs in order to complete the present investigation were: 1000 mg/kg for vitamin E, and 10 mg/kg for rosuvastatin. The test agents were daily administered for 14 days in normal and amikacin-treated rats. Nephrotoxicity was induced through a single i.p. injection of amikacin on twelvth day.
Biochemical analysis includes determination of serum urea nitrogen, creatinine, albumin as well as total protein as kidney function tests. In addition, kidney contents of malondialdehyde (MDA) and reduced glutathione (GSH) as well as enzymatic activity of catalase (CAT) were evaluated as oxidative stress biomarkers. The inflammatory mediators, TNF-α and Nrf-2 in kidney tissue were also assessed. Furthermore, histopathological study was performed to confirm the biochemical findings.
The main findings of the present study are summarized as follow:
A. Effect of amikacin on the measured parameters:
1. Regarding the kidney function biomarkers, amikacin significantly increased serum levels of urea nitrogen (BUN), creatinine, while it significantly decreased albumin and total protein as compared to control saline group.
2. Amikacin significantly reduced renal content of glutathione (GSH), as well as enzyme activity of catalase (CAT) levels and significantly induced renal content malondialdehyde (MDA) as compared to control saline group.
3. It also significantly raised renal tumor necrosis factor (TNF)-α, and nuclear transcriptional factor (Nrf)-2 as compared to control saline group.
4. DNA fragmentation% was increased in amikacin-treated rats as compared to control saline group explaining that amikacin induced oxidative stress leading to DNA damage in the kidneys of rats.
5. Amikacin induced severe histopathological and morphological alterations in kidney tissue.
B. Effect of vitamin E, rosuvastatin or their combination on amikacin-induced nephrotoxicity:
1. Pretreatment with Vit E, rosuvastatin or their combination significantly reduced serum levels of UN and creatinine in association with increased serum albumin and total protein levels as compared to amikacin group.
2. Vit E, rosuvastatin or their combination ameliorated amikacin induced nephrotoxicity by restoration of renal pro-oxidant/antioxidant balance via enhancement of renal GSH content and CAT activity. On the other hand, they hampered the renal MDA content as compared to amikacin group.
3. Vit E, rosuvastatin or their combination significantly decreased renal TNF-α, and (Nrf)-2, as circulatory markers of inflammation as compared to amikacin group.
4. Vit E, rosuvastatin or their combination enhanced the survival of renal tubular cells by reducing DNA fragmentation and necrosis as compared to amikacin group.
5. Microscopically, Vit E, rosuvastatin or their combination prevented amikacin-induced degenerative changes and inflammatory cell infiltration. Furthermore, it reduced tubular necrosis and preserved glomerular and proximal tubular integrity as compared to amikacin group.
According to the previous findings it could be concluded that:
1. Amikacin administration produced severe nephrotoxicity in rats which could be attributed to disturbance in oxidant/antioxidant balance besides induction of inflammation and producing severe histopathological alterations in kidney tissue manifested as apoptotsis.
2. On the other hand vitamin E, rosuvastatin or their combination could ameliorate amikacin-induced kidney injury that might be attributed to potent antioxidant, anti-inflammatory as well as anti-apoptotic activities. They could be promising agents for clinical use as nephroprotectants against amikacin-induced nephrotoxicity.