الفهرس 
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Abstract
Summary and conclusion
The present experimental study was designed to evaluate the effect of saxagliptin on cisplatin induced nephrotoxicity in rats.
Twenty-four adult male albino rats matched for age (3- 4 months) and weight (150-250g) were used. The rats were divided into four groups. Each group contained 6 rats. group (1) Normal control group: rats received 0.9% NaCl in tween 80 I.P for 14 days. group (2) Saxagliptin treated group: normal rats received saxagliptin (12.5mg/kg) in tween 80 daily IP for 14 days. group (3) Cisplatin treated group: rats received cisplatin on the 8th day (5mg /kg, IP single injection). This group serves as a model of CP induced nephrotoxicity. group (4) Saxagliptin andCisplatin treated group: rats received saxagliptin by the same previous dose, and route of administration 7days before and 7 days after IP single injection of cisplatin. Cisplatin was given by the same previous dose. Rats were sacrificed after the 7th day from cisplatin injection. The following biochemical parameters were measured in the left kidney tissue homogenate GSH, Catalase, MDA, DDP4 enzyme level, and TNFα. Urea, and Creatinine were measured in serum. Also, Urine volume, Albumin, Creatinine, Albumin /creatinine ratio were measured in urine.
Body weights of the rats used in different groups were determined at the start and at the end of the experiment and the percentage of changes in their body weights were calculated.
The weights of both kidneys (absolute weight) and the relative kidney weights were estimated. In addition to histopathological examination of the right kidney tissue.
The obtained data from the present study showed that
Oxidative stress (GSH, Catalase, MDA)
saxagliptin in cisplatin pretreated group (group 4) has anti-inflammatory and antioxidative stress effects, these findings were determined by alleviation of changes caused by cisplatin which significantly decrease renal tissue content of GSH and catalase in cisplatin treated group compared to the normal control group.
On the other hand, cisplatin significantly increases MDA level in cisplatin treated group compared to the normal control group, while cisplatin pretreated group by saxagliptin showed significant increase in renal tissue content of GSH and catalase and significant decrease in MDA level.
Anti- inflammatory markers (TNFα)
renal tissue content of TNFα increased significantly in the cisplatin -treated group compared to the normal control group. Cisplatin group pretreated with saxagliptin revealed a significant alleviation of this increase compared to the cisplatin group.
DPP-4 enzyme
the renal tissue content of DPP4 enzyme increased significantly in the cisplatin- treated group compared to the normal control group. Cisplatin group pretreated with saxagliptin revealed a significant amelioration of this increase in the level of DPP4 enzyme compared to the cisplatin-treated group value.
kidney functions
the current study showed that urinary level of albumin and albumin / creatinine ratio increase significantly in the cisplatin-treated group compared to the normal control group. Also, cisplatin significantly decreased the urine volume and urinary creatinine compared to normal control group. Cisplatin group pretreated with saxagliptin revealed a significant alleviation of these changes compared to the cisplatin group.
The percentage of changes in body weights
the control group revealed significant increase in the percentage of changes in the body weight at the end of the experiment versus significant decrease among the cisplatin group, saxagliptin treated group and the cisplatin pretreated group by saxagliptin.
Kidney weights
There was no significant change in the relative kidney weight, while there was a significant increase in the absolute kidney weight in the cisplatin treated group compared to normal control group.
In addition, the findings of histopathological examinations confirmed the biochemical data.
The present study suggests the following conclusions.
- Saxagliptin has antioxidant effects as evidenced by alleviation of decrease GSH and catalase level and alleviation of increase MDA level in kidney tissue homogenate induced by cisplatin.
- Saxagliptin has anti -inflammatory effects as evidenced by alleviation of increase TNF alpha, DPP-4 enzyme levels induced by cisplatin. Also, Saxagliptin decrease the absolute kidney weight and improved renal functions.
- Saxagliptin improved the histopathological changes induced by cisplatin as evidenced by general improvement of the histopathological picture regarding inflammatory cell infiltration and necrosis of renal tubules.
The following conclusions suggests that saxagliptin protected against cisplatin-induced nephrotoxicity via long lasting inhibition of DPP4 enzyme and its tight covalent binding.
Further studies are needed with different doses and may be for longer duration, on a larger sample size to fully investigate the effect of saxagliptin on cisplatin induced nephrotoxicity. Also, more studies targeting the side effects of saxagliptin should be addressed.