الفهرس 
INTRODUCTION AND AIM OF THE WORK
The kidneyOnly 14 pages are availabe for public view
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Abstract
To date, an overwhelming production of oxidative stressors resembles the most considerable effector in DOX induced nephrotoxicity. A solid body of evidence indicates that DOX-driven oxidative stress, if remain unopposed, can undoubtedly upset the cellular redox balance initiating apoptosis and inflammatory cascades that eventually threaten the cell’s survival. Over years, silencing these DOX-initiated oxidative stressors and their undesirable consequences was considered as one of the most aggressively pursued goals to overcome its use associated drawbacks. Although individual phytochemical remedies achieved partial successes in this respect, a satisfactory outcome has not reached yet.
In the current study, QUR and BER were investigated individually and in combination to withstand against DOX-induced nephrotoxicity in rats which was induced by single intravenous DOX injection (7.5 mg/kg). Oral administrations of QUR (50 mg/kg) alone or BER (50 mg/kg) alone as well as a blend of them in the same doses were started one week before DOX injection and continued concomitantly for another 14 consecutive days. On day 15 after DOX administration, each animal was housed in an individual metabolic cage for urine collection. One day later, blood samples and both kidneys were collected and the animals were sacrificed.
I. Biochemical analysis
1. Serum creatinine, BUN and microalbuminuria were estimated by colorimetric procedures using the corresponding kits.
2. Urinary Kim-1 level was achieved by using rat specific ELISA kit.
3. Tissue levels of reduced glutathione (GSH), Superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels were assessed by using the colorimetric procedures.
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Summary and conclusion
II. Molecular estimation:
1. Investigation of p53 expression in renal tissues was carried out by western blotting analysis.
2. The mRNA expression of caspase-3, Bcl-xl and interleukin-18 in renal tissues was measured by using RT-PCR.
Conclusion
Regarding biochemical results we concluded that:
1. Changes in renal tissue contents of MDA, NO, GSH and SOD activity suggested that DOX-motivated ROS resembles the most considerable effectors in DOX-induced nephrotoxicity.
2. Changes in the levels of urinary Kim-1 could be correlated with the AKI severity and could be used as predictor of AKI.
Regarding molecular markers, we concluded that:
1. DOX has a prominent role in leading cells towards apoptotic death.
2. DOX exposure induced renal expression of two common pro-apoptotic markers, p53 and caspase-3
3. Concomitantly DOX diminished renal expression of Bcl-xL, a leading member in the anti-apoptotic gene family.
4. DOX can cause injurious effects through its perturbed expression of IL-18,
maintaining an inflammatory environment leading to tissue kidney injury.
Pre- and co-treatment with QUR and BER relatively buffered the nephrotoxic effects of DOX indicating indubitable reno-protective effect of these phytochemicals.
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Summary and conclusion
The results of present study may have identified for the first time that QUR in combination with BER shows better alleviation of DOX-induced kidney injury than their individual administration.
A solid body of evidence indicates that this undeniable reno-protective effects
could be attributed to the synergistic antioxidant, anti-apoptotic and anti-inflammatory activities of this dual phytochemical remedy that lead to :
a. Abrogation of DOX-induced ROS generation.
b. Modulation of the DOX-induced apoptotic signals.
c. Amelioration of DOX-induced inflammatory cascade.
Recommendations
Further pharmacokinetic studies are required to expand understanding of this synergism between QUR and BER and to build a foundation for later extension of their cytoprotective capacity in binary administration against other organotoxicities.