Document Details
|
Document Type |
: |
Thesis |
|
Document Title |
: |
Effect of “Toll Like Receptors (TLR-4)” Inhibitor(s) on Lipopolysaccharide-Induced Acute Kidney Injury in Mice تأثير مثبطات مستقبلات (TLR-4) على إصابة الكلى الحاد المحدث بواسطة ليبوبوليسكاريد في الفئران |
|
Subject |
: |
Faculty of medicine |
|
Document Language |
: |
Arabic |
|
Abstract |
: |
Background: Acute kidney injury occurs when kidney function suddenly decreases, resulting in the build-up of waste products and significant increases in mortality and morbidity. It is frequently diagnosed in critically sick patients and its predictable prevalence is up to 50% in the intensive critical unit patients. Thus, it is critical to investigate novel therapy options for preventing the epidemic. In which toll-like receptor-4 and inflammation known to have an important part in the deterioration of acute kidney injury. Resatorvid is a small molecule that inhibits the production of inflammatory cytokines caused by pathogens, works by inhibiting TLR-4- signaling. The impact of Resatorvid on acute kidney injury has not been clearly elucidated.
Objectives: To assess the possible impact of Resatorvid, a Toll-like receptor-4 inhibitor, against lipopolysaccharide -induced acute kidney injury in mice as well as elucidate the involved mechanisms with respect to inhibition of pro-inflammatory cytokines and Toll-like receptor-4 expression.
Methods: Single injection of lipopolysaccharide (5 mg/kg, intraperitoneally) was used to cause acute kidney injury in mice. Animals were divided into the control, (acute kidney injury), (acute kidney injury + Resatorvid, 3 or 10 mg/kg), (Resatorvid - 10mg/kg alone). Kidney injury was evaluated by histopathological examination and measuring renal function biomarkers. The oxidative state, the concentration of pro-inflammatory and anti-inflammatory cytokines and chemokines in the kidney tissue of mice were measured. The expression of the toll-like receptor-4 and the phosphorylated nuclear factor Kappa B cell proteins were examined by using immunohistochemistry in kidney homogenates. The activity of angiotensin converting enzyme 2 was also measured.
Results & Discussion: Resatorvid has shown to alleviate symptoms of acute kidney injury, improving the renal function biomarkers and alleviate kidney structural abnormalities, in a dose-related manner. In addition, improve oxidative stress, and reduce the concentration of inflammatory biomarkers in the kidneys of mice. It also enhanced the activity of angiotensin converting enzyme 2.
Conclusion: The results show that Resatorvid significantly reduced kidney inflammation and renal function impairment in mice, which was associated with down-regulation of toll-like receptor-4. Clinical studies on Resatorvid in the treatment of acute kidney injury are encouraged.
Keywords: Inflammation, angiotensin converting enzyme 2, Resatorvid, toll-like receptor-4, acute kidney injury. |
|
Supervisor |
: |
Dr. Ahmed Esmat Amer |
|
Thesis Type |
: |
Master Thesis |
|
Publishing Year |
: |
1445 AH
2023 AD |
|
Co-Supervisor |
: |
Dr. Mohammed Alsieni |
|
Added Date |
: |
Saturday, November 4, 2023 |
|
Researchers
| ميعاد عابد المزمومي | Almazmomi, Meaad Abid | Researcher | Master | |
|
Back To Researches Page
|