Cardioprotective effect of pioglitazone and curcumin against diabetic cardiomyopathy in type 1 diabetes mellitus: impact
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ORIGINAL ARTICLE
Cardioprotective effect of pioglitazone and curcumin against diabetic cardiomyopathy in type 1 diabetes mellitus: impact on CaMKII/NF-κB/TGF-β1 and PPAR-γ signaling pathway Aya A. Gbr 1 & Nayira A. Abdel Baky 2
&
Eman A. Mohamed 2 & Heba S. Zaky 2
Received: 10 June 2020 / Accepted: 16 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients, which is currently without available specific treatment. This study aimed to investigate the potential protective effects of pioglitazone (Pio) and curcumin (Cur) against DCM in type 1 diabetes mellitus (T1DM), with pointing to their role on Ca+2/calmodulin-dependent protein kinase II (CaMKII) and peroxisome proliferator–activated receptor gamma (PPAR-γ) expression. Diabetes was induced in adult male Sprague Dawley rats by administration of single intraperitoneal injection of streptozotocin (STZ) (52.5 mg/kg). Diabetic rats were administered either Pio (20 mg/kg/day) or Cur (100 mg/kg/day) orally for 6 weeks. Treatment with Pio and/or Cur markedly reduced serum cardiac injury markers and lipid profile markers in diabetic animals. Additionally, Pio and/or Cur treatment mitigated oxidative stress and fibrosis in diabetic rats as evident from the significant suppression in myocardial lipid peroxidation and tumor growth factor beta 1 (TGF-β1) level, with concomitant significant elevation in total antioxidant capacity (TAC) and improvement in histopathological architecture of heart tissue. Pio/Cur treatment protocol accomplished its cardioprotective effect by depressing cardiac CaMKII/ NF-κB signaling accompanied by enhancement in PPAR-γ expression. Conclusively, these findings demonstrated the therapeutic potential of Pio/Cur regimen in alleviating DCM in T1DM through modulation of CaMKII and PPAR-γ expression. Keywords Diabetic cardiomyopathy . Curcumin . Pioglitazone . Streptozotocin . Ca+2/calmodulin-dependent protein kinase II . Peroxisome proliferator–activated receptors gamma
Introduction Diabetic cardiomyopathy (DCM) is a serious complication that affects diabetic individuals with increasing prevalence in patients with type 1 diabetes mellitus (T1DM) (Abdelsamia et al. 2019). Until now, there is no specific treatment for DCM because of the complexity of its underlying pathogenesis that Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01979-y) contains supplementary material, which is available to authorized users. * Nayira A. Abdel Baky [email protected]; [email protected] 1
Egypt Ministry of Health and Population, Cairo, Egypt
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Naser City, Cairo P.N.11754, Egypt
includes altered calcium (Ca+2) homeostasis, neurohormonal activation, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, inflammation, myocardial fibrosis, and apoptosis (Jia et al. 2018;
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