الفهرس 
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Abstract
Acute kidney injury (AKI), previously known as ARF, is a rapid decline in kidney function that occurs over hours to days. This is in contrary to chronic kidney disease, where renal function declines over months to years. AKI is an independent risk factor associated with mortality in critically ill patients, mainly as a component of multiple organ dysfunction in patients with severe sepsis. It is a common and devastating clinical problem with an in-hospital mortality of 40–80% in intensive care units.
Flavonoids are an essential component that is related to a broad spectrum of health-promoting effects. Among the various flavonoids is morin, a bioactive compound abundant in the plants of the Moraceae family in particular. Ongoing research has demonstrated that the administration of morin has not associated with any adverse side effects. Moreover, it is comparatively cost-effective and easily available. Morin showed anti-inflammatory, and antioxidant activities in various nephrotoxicity models including those induced by mercuric chloride, gentamicin, cisplatin, doxorubicin, and acrylamide. from the previous studies, it is evident that morin is capable of modulating the level of MDA and increasing the endogenous antioxidant defense mechanisms in case of SI-AKI. These observations may direct our attention towards the possibility that morin may be of therapeutic value in the treatment of sepsis-induced AKI.
Thus, the present work was designed considering three aims:
1. the first is to evaluate the effect of morin on the survival rate of septic mice.
2. the second aim is to investigate the potential role of morin to ameliorate acute kidney injury, and to assess the mechanism of its action.
3. the third aim is to estimate the difference between the septic recovery group and morin-treated recovery group.
In the current study, a total of sixty healthy adult male mice were used. One week after the acclimatization period, the animals were randomly assigned into six groups (each of 10 mice), as follows:
group I (negative control group): normal mice, neither treated with morin nor challenged with LPS.
group II (Morin group): mice orally treated with morin hydrate at a daily dose of 50 mg/kg b.wt for 3 consecutive days.
group III (LPS group): LPS-challenged mice to establish septic AKI model. Mice were intraperitoneally injected with a single injection LPS after 16 hrs of starvation, at a dose of (5 mg/kg in PBS).
group IV (LPS+ Morin group): mice were challenged with LPS, then orally treated with morin hydrate (50 mg/kg). Treatment with morin started 3 hrs after LPS challenge, then for 2 more days.
group V (LPS recovery group): LPS-challenged mice were sacrificed at the 7th day after LPS challenge.
group VI (LPS + Morin recovery group): LPS-challenged mice, treated with morin for 3 days, then sacrificed at the 7th day after LPS challenge.
At the end of the experiment, blood and kidney samples was collected and subjected to different analyses according to the following protocol:
Biochemical analyses to assess the effect of morin on SCr, BUN, ALB, AP, Na+ and K+, in addition to kidney MDA and TAC.
Histopathological studies to assess the effect of morin on the pathological characteristics of renal tissue of septic mice.
Ultrastructural studies to assess the effect of morin on the ultrastructure of renal tissue of septic mice.
Immunohistochemical studies to assess the effect of morin on (TNF-α: proinflammatory marker, BCl2: surviving cell marker, VEGF: the endothelial pro-inflammatory and cell permeability marker, and vimentin: marker for tubular injury and epithelial-to-mesenchymal transition).
Analyses were performed by SPSS version 16 software for Windows (SPSS, Chicago, IL). Data were expressed as mean ± SEM. Differences between groups were tested for statistical significance using two-ways analysis of variance (ANOVA), followed by Tukey’s test. P < 0.05 was considered significant for all data analyses.
The results of the current study showed that the survival rate in septic control group was significantly lower compared with other groups, and rated 44%. Treating septic mice with morin increased the survival rate of the treated mice to 80%, and the recovery from the clinical symptoms of sepsis.
In biochemical results septic mice showed significant increase in serum BUN, Cr, AP and K+, as well as tissue MDA concentrations when compared with those of the negative control group. Meanwhile, the same group showed significant decrease in the levels of ALB, Na+ and TAC concentrations compared with those of the negative control group. However, treating septic mice with morin significantly ameliorated the biochemical results compared with septic control group.
Histological results showed that all septic mice exhibited altered renal histological architecture manifested by disorganized, deformed and atrophied renal tubules and corpuscles. Morin-treated septic mice showed slight architectural alterations. The glomeruli restored normal appearance and size.
Ultrastructural results showed that the kidneys of septic group exhibited ultrastructural changes in tubular and glomerular cells. The morphological changes were manifested by degradation of the components of the tubular cell and glomeruli. Treatment with morin led to a restoration of the tubular and glomerular ultrastructure in the septic kidneys.
The effect of morin on the immunoexpression of TNF-α, BCl2, VEGF, and vimentin antibodies was evaluated in the renal tissues. In septic kidney sections, the immunoexpression of these markers was stronger than their expression in normal group. On the other hand, septic tissues treated with morin restored the immunoexpression of markers.
In conclusion,
Morin has a significant therapeutic effect on sepsis-induced AKI mice via reducing the mortality rate, preventing the oxidative stress that lead to decrease in immunoexprission of BCl2, vimentin, and VEGF, preventing production of proinflammatory cytokines TNF-α, enhancing the renal function, histology and ultrastructure.