الفهرس 
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Abstract
In the present study, the nephroprotective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in adult female mice were studied. The test drugs were given for normal as well as cisplatin-treated mice for 7consecutive days. Nephrotoxicity was induced through cisplatin injection as a single dose of 7.5 mg/kg, i.p. on the 5th day after drug administration. The degree of nephrotoxicity was assessed by measuring kidney function tests such as serum levels of creatinine and blood urea nitrogen (BUN). Furthermore, serum malondialdehyde (MDA),reduced glutathione (GSH) content, as well as serum catalase activity were evaluated as oxidative stress biomarkers. Serum tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6), cyclooxygenases I, II (COX I, COX II) levels were measured as indicators for inflammation. Serum caspase-3 (CASPASE-3) was measured also as indicator for apoptosis. Histopathological study was performed to confirm the biochemical findings.
The main findings of the present study can be summarized as follows:
1. Apigenin, myricetin or their combination did not significantly affect serum levels of creatinine and BUN in normal animals.
2. Cisplatin caused a significant increase in serum levels of creatinine and BUN.
3. Apigenin, myricetin or their combination significantly ameliorated cisplatin-induced elevation in serum creatinine and BUN levels.
4. Apigenin, myricetin or their combination did not significantly affect serum contents of MDA, GSH, CASPASE-3, TNF-α, IL-6, COX I, COX II as well as catalase activity in normal mice.
5. Cisplatin significantly elevated serum MDA content, CASPASE-3, TNF-α, IL-6 levels while significantly reduced serum GSH content, catalase activity and COX I, COX II levels.
6. Apigenin, myricetin or their combination significantly reduced the cisplatin-induced elevation of serum MDA content, CASPASE-3, TNF-α, IL-6 levels while significantly increased cisplatin-induced reduction of serum GSH content, catalase activity and COX I, II levels.
7. Histopathological examination of kidney tissue of mice treated with apigenin, myricetin or their combination did not show any significant disruption of the normal kidney patterns.
8. Histopathological examination of the group treated with cisplatin showed kidney damage manifested by severe and widespread necrosis with dilatation of proximal tubules that lead to loss of tubular architecture, vacuolization, tubular cell desquamation and intraluminal cast formation as compared to the normal control group.
9. Histopathological examination of groups treated with apigenin and myricetin prior to cisplatin treatment showed less histopathological renal changeswith very mild congested blood vessels and very mild tubular dilatation as compared to cisplatin group.
10. Histopathological examination of groups treated with combination of apigenin and myricetin prior to cisplatin treatment showing nearly normal structure of the kidney.
from the previous findings it could be concluded that:
1. Cisplatin produces severe nephrotoxicity in mice.
2. Apigenin and myricetin could be promising agents for clinical use as nephroprotectants against cisplatin-induced nephrotoxicity due to their antioxidant, anti-inflammatory and antiapoptic effects.
3. Further clinical investigations are needed to ensure the efficacy and safety of apigenin and myricetin and to explore the possible interfering of these drugs with the antitumor activity of cisplatin.