Abstract
Purpose: To investigate the possible cardioprotective effects and potential pharmacological mechanism of genistein.Methods: Six-week old ZDF and lean rats were randomized into 4 groups (8 rats/group), including group 1 (control lean rats); group 2 (lean rats treated with genistein, 2.5 mg/kg); group 3 (control ZDF rats); and group 4 (ZDF treated with genistein). Two groups (2 and 4) were treated with genistein for 12 weeks, and cardiac functions and metabolic alterations were determined. Macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription level also were observed.Results: Genistein attenuated diabetes-induced cardiac dysfunction and pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signalling pathways. In addition, genistein treatment markedly reduced diabetic-induced MCP-1 (83.33 %), VCAM-1 (74.66 %) and ICAM-1 (71.42 %) secretion and mRNA transcription in ZDF rats.Conclusion: The results demonstrate the putative effects of genistein against cardiovascular dysfunction by improving glucose homeostasis, attenuating oxidative stress and reduced diabeticinduced endothelial dysfunction in ZDF rats. Thus, genistein is a potential candidate for the prevention of cardiovascular diseases.Keywords: Cardiac dysfunction, Genistein, Oxidative stress, Inflammatory response, Insulin resistance, Glucose tolerance
Highlights
The American Heart Association considers diabetes to be one of the seven major controllable risk factors for cardiovascular disease
Diabetic induced cardiovascular disease was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NFκB signalling and diminished Akt phosphorylation, along with decreased glucose transport, increased cardiac lipid accumulation, and diastolic dysfunction [1,2]
The mRNA levels in untreated ZDF rats showed a marked increases of monocyte chemo-attractant protein-1 (MCP-1) (9.09 %), vascular cellular adhesion molecule-1 (VCAM-1) (20 %) and intracellular adhesion molecule-1 (ICAM-1)(21.42 %) secretion compared with lean (p < 0.05); treatment with genistein would significantly inhibit MCP-1 (83.33 %), VCAM-1 (74.66 %) and ICAM1 (71.42 %) secretion compared with ZDF rats (Fig 4A)
Summary
The American Heart Association considers diabetes to be one of the seven major controllable risk factors for cardiovascular disease. Diabetic induced cardiovascular disease was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NFκB signalling and diminished Akt phosphorylation, along with decreased glucose transport, increased cardiac lipid accumulation, and diastolic dysfunction [1,2]. The most prevalent cardiovascular complications of diabetes, characterized by both systolic and diastolic dysfunction, due to reduced contractility, prolonged relaxation and decreased compliance, are diabetic cardiomyopathy [3] and atherosclerosis [4]. Endothelial impairment can be detected in the early stage of atherosclerosis and serves as one of the leading mechanisms for HHcy-induced vascular dysfunction [8,9]. Body weight and fasting glucose levels were measured weekly. The GTT, D-glucose (2 g/kg body weight, Sigma Aldrich) was orally administrated after overnight fasting. Comparisons between groups were tested by One-Way ANOVA analysis; p < 0.05 was considered statistically significant
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
