The Potential Protective Effects of Diosmin on Streptozotocin-Induced Diabetic Cardiomyopathy in Rats

Am J Med Sci. 2020 Jan;359(1):32-41. doi: 10.1016/j.amjms.2019.10.005. Epub 2019 Oct 22.

Abstract

Background: Diabetic cardiomyopathy (DCM) is a nonischemic myocardial disorder characterized by metabolic disturbances and oxidative stress in diabetic patients. The present paper aims to determine the protective effect of the phlebotrophic drug, diosmin, on DCM in a model of high-fat diet-fed and streptozotocin-induced type 2 diabetes in the rat.

Materials and methods: The animals were divided into 4 groups (8 rats/group) as follows: vehicle-treated nondiabetic control group, vehicle-treated diabetic group, diosmin (50 mg/kg)-treated diabetic group and diosmin (100 mg/kg)-treated diabetic group. Treatment was given once daily orally by gavage for 6 weeks. Oxidant and antioxidant stress markers, inflammatory markers and proapoptotic and antiapoptotic gene expression using quantified real-time polymerase chain reaction were investigated.

Results: Diosmin treatment in diabetic rats lowered elevated blood glucose levels, homeostatic model assessment for insulin resistance, cardiac creatine kinase and lactate dehydrogenase enzymes, cardiac malondialdehyde and nitric oxide. Moreover, diosmin increased plasma insulin and c-peptide levels, cardiac glutathione content, superoxide dismutase, catalase and glutathione S-transferase activities. Also, diosmin treatment significantly (P < 0.05) lowered the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), down-regulated cardiac Bcl-2-associated X protein and caspase 3 and 9 and up-regulated B-cell lymphoma 2 mRNA expression levels.

Conclusions: Diosmin may have a sizeable therapeutic potential in the treatment of DCM due to antidiabetic, antioxidative stress, anti-inflammatory and antiapoptotic effects. Detailed studies are needed to disclose the precise mechanisms motivating the protective effect of diosmin‏.

Keywords: Cardiomyopathy‏; Diosmin; High-fat diet; Streptozotocin-diabetes type-2.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Biomarkers / blood
  • Blood Glucose
  • C-Peptide / blood
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Cardiomyopathies / prevention & control*
  • Diosmin / administration & dosage
  • Diosmin / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Homeostasis
  • Insulin / blood
  • Insulin Resistance
  • Rats

Substances

  • Biomarkers
  • Blood Glucose
  • C-Peptide
  • Insulin
  • Diosmin