Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R
This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was...
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doaj-f21efc3c491b457389120a41fcbca5712021-02-05T15:30:23ZengElsevierSaudi Pharmaceutical Journal1319-01642021-01-012912742Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase RJozaa Z. ALTamimi0Mona N. BinMowyna1Nora A. AlFaris2Reham I. Alagal3Attalla F. El-kott4Ammar M. AL-Farga5Nutrition and Food Science (PHD), Department of Physical Sport Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaCollege of Applied Medical Sciences, Shaqra University, Shaqra, Saudi ArabiaNutrition and Food Science (PHD), Department of Physical Sport Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaNutrition and Food Science (PHD), Department of Physical Sport Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Corresponding author at: P.O. Box 2460, Riyadh 11451, Saudi Arabia.Department of Biology, College of Science, King Khalid University, Abha, Saudi ArabiaDepartment of Biochemistry, College of Sciences, University of Jeddah, Jeddah, Saudi ArabiaThis study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR.http://www.sciencedirect.com/science/article/pii/S1319016420302784FisetinDiabetic cardiomyopathyProtein Kinase RGlucoseRats |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jozaa Z. ALTamimi Mona N. BinMowyna Nora A. AlFaris Reham I. Alagal Attalla F. El-kott Ammar M. AL-Farga |
spellingShingle |
Jozaa Z. ALTamimi Mona N. BinMowyna Nora A. AlFaris Reham I. Alagal Attalla F. El-kott Ammar M. AL-Farga Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R Saudi Pharmaceutical Journal Fisetin Diabetic cardiomyopathy Protein Kinase R Glucose Rats |
author_facet |
Jozaa Z. ALTamimi Mona N. BinMowyna Nora A. AlFaris Reham I. Alagal Attalla F. El-kott Ammar M. AL-Farga |
author_sort |
Jozaa Z. ALTamimi |
title |
Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R |
title_short |
Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R |
title_full |
Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R |
title_fullStr |
Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R |
title_full_unstemmed |
Fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase R |
title_sort |
fisetin protects against streptozotocin-induced diabetic cardiomyopathy in rats by suppressing fatty acid oxidation and inhibiting protein kinase r |
publisher |
Elsevier |
series |
Saudi Pharmaceutical Journal |
issn |
1319-0164 |
publishDate |
2021-01-01 |
description |
This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR. |
topic |
Fisetin Diabetic cardiomyopathy Protein Kinase R Glucose Rats |
url |
http://www.sciencedirect.com/science/article/pii/S1319016420302784 |
work_keys_str_mv |
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