Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats

Thesis
, Abeer M. Alanazi , Laila Fadda , Ahlam Alhusaini , Rehab Ahmad , Iman H. Hasan and Ayman M. Mahmoud . 2020
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Abstract: Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects,particularlycardiacdysfunction. Thisstudyexaminedthecardioprotectiveeffectsofcarvedilol (CAR)and/orresveratrol(RES)andliposomalRES(LIPO-RES)againstDOX-inducedcardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week2toweek6. DOX-administeredratsexhibitedasignificantincreaseinserumcreatinekinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidationwasincreasedinDOX-administeredrats. TreatmentwithCAR,RESorLIPO-RESaswell as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, andtheexpressionofS100A1andSERCA2a. Inconclusion,thepresentstudyconferrednewevidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.

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