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PI3K / AKT / GSK-3β Pathway Mediates the Ameliorative Effect of Amentoflavone on Hepatorenal Injury Induced by Doxorubicin.

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  • معلومة اضافية
    • نبذة مختصرة :
      Background: Doxorubicin (DOX) induced hepatorenal injury is a major health concern. Amentoflavone (AMF) is a biflavonoid with conspicuous pharmacological activities. Objective: To clarify the possible protective AMF effect on DOX associated hepatorenal injury & the possible underlying mechanisms. Material and methods: 30 rats were equally divided to three groups: control group. DOX group and DOX+AMF treated. After that blood samples were withdrawn for assessment of serum urea, creatinine, ALT, AST, MDA, TNF-α, caspase-3, SOD and IL10. Liver and kidney were preserved for AKT, PI3K and GSK-3β genes expression level detection. Finally, Histopathological assessment of hepatic and renal section was done. Results: DOX group revealed a significant increase in urea, creatinine, ALT, AST, MDA, TNF-α, and caspase-3, along with a concurrent decrease in SOD and IL10 when compared to control rats. Serum levels of urea, creatinine, ALT, AST, MDA, TNF-α, caspase3 were significantly reduced, and SOD and IL10 were significantly increased in the DOX+AMF group compared to DOX group, while there was a significant reduction in the expression of the AKT and PI3K genes and a concurrent increase in the expression of the GSK-3β gene with DOX treatment. AMF significantly mitigated the expression of the AKT and PI3K genes with reduction of GSK-3β gene after 8 weeks. Conclusion: AMF protects against doxorubicin induced hepatorenal injury by antioxidant, anti-inflammatory, antiapoptotic mechanisms in addition to modulation in PI3K/AKT/GSK-3β signaling pathway. [ABSTRACT FROM AUTHOR]
    • نبذة مختصرة :
      المقال يركز على التأثيرات الوقائية للأمينتوفلافون (AMF) ضد إصابة الكبد والكلى الناتجة عن دوكسوروبيسين (DOX) من خلال تعديل مسار الإشارات PI3K/AKT/GSK-3β. شملت الدراسة 30 جرذًا من نوع ويستار (Wistar) الذكور مقسمة إلى ثلاث مجموعات: مجموعة ضابطة، مجموعة DOX، ومجموعة معالجة بـ DOX+AMF. أظهرت النتائج أن AMF قلل بشكل كبير من علامات تلف الكبد والكلى، وحسن النتائج النسجية المرضية، وعدل تعبير الجينات الرئيسية المعنية بالإجهاد التأكسدي والالتهاب، مما يشير إلى إمكانيته كعامل وقائي كيميائي ضد سمية DOX. [Extracted from the article]