Document Details
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Document Type |
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Thesis |
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Document Title |
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Effect of Kaempferol on Nephrotoxicity and Hyperglycemia Experimentally Induced by Tacrolimus and Prednisolone تأثير الكيمبفيرول على ارتفاع السكر بالدم والسمية الكلوية المحدثة تجريبيا باستخدام التاكروليمس والبردنيزولون |
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Subject |
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Faculty of medicine |
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Document Language |
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Arabic |
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Abstract |
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Background: The kidney and pancreas are susceptible organs to adverse drug effects, especially in post-transplantation conditions. Nephrotoxicity and hyperglycemia are severe complications following chronic Tacrolimus (FK506) and Prednisolone (Pred) use. As a natural flavonoid, Kaempferol (KMF) has many biological activities, including antioxidant action.
Objectives: To ameliorate FK506 and Pred induced nephrotoxicity and hyperglycemia and explore the potential contributing factors.
Methods: Forty male albino-Wistar rats were randomly divided into five equal groups. Control group received vehicles (0.1 ml propylene glycol, i.p.) and (0.5 ml 0.5% carboxymethyl cellulose, PO), Group(2) injected with FK506 (0.6 mg/kg, i.p.), Group(3) administered FK506 (0.6 mg/kg, i.p.) and KMF (10 mg/kg, PO), Group(4) received FK506 (0.6 mg/kg, i.p.) and Pred (2 mg/kg, PO), Group(5) administered FK506 (0.6 mg/kg, i.p.), Pred (2 mg/kg, PO), and KMF (10 mg/kg, PO). Treatment regimen for all groups was once a day for 30days. ELISA technique applied for measurement of FK506 trough level and nephrotoxicity/hyperglycemia biomarkers in serum (cystatin C, urea, glucose, insulin) on days 15&30, and tissues homogenate (glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), P-glycoprotein (P-gp), calcineurin B1 (CnB1)) on day30.
Results: In FK506 and Pred treated rats, on day30, the FK506 trough level was (5.84 ± 1.38 ug/l). Nephrotoxicity and hyperglycemia biomarkers in serum significantly (P<0.001) aggravated while in kidney and pancreas tissue, MDA level showed a significant increase (P<0.01; 355% and 488%) coupled with a remarkable decrease in CnB1 (60% and 58.5%). KMF combination significantly (P<0.05) ameliorated serum urea (34%), cystatin C (25%), glucose (33%), insulin (303%), renal GSH (200%), renal CnB1(157%), and pancreatic CnB1 (103.3%, P=0.102).
Conclusion: Oxidative stress and CnB1 are contributing factors in nephrotoxicity and hyperglycemia. Hence, inhibition of calcineurin enzyme is not limited to the immune cells. KMF could be a novel nephroprotective and hypoglycemic antioxidant when combined with FK506 and Pred. |
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Supervisor |
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prof. Ahmed Shaker Ali |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1442 AH
2020 AD |
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Co-Supervisor |
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prof. Basma Tarek Alharthy |
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Added Date |
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Sunday, March 14, 2021 |
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Researchers
| عبدالله سداح المالكي | Almalki, Abdullah Saddah | Researcher | Master | |
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