Suppression of HDAC by sodium acetate rectifies cardiac metabolic disturbance in streptozotocin-nicotinamide-induced diabetic rats
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Date
2020-03-17
Journal Title
Journal ISSN
Volume Title
Publisher
Society for Experimental Biology and Medicine
Abstract
Diabetes mellitus, particularly type 2 occurs at global epidemic proportions and leads to
cardiovascular diseases. Molecular studies suggest the involvement of epigenetic altera tions such as histone code modification in the progression of cardiometabolic disorders.
However, short chain fatty acids (SCFAs) are recognized as epigenetic modulators by their
histone deacetylase inhibitory property. It is therefore hypothesized that cardiac histone
deacetylase activity increases in type II diabetes and SCFA, acetate, would inhibit histone
deacetylase with accompanying restoration of glucose dysregulation, cardiac lipid deposi tion, and tissue damage in male Wistar rats. Twenty-four male rats (240–270 g) were allotted
into four groups (n ¼ 6 per group) namely: vehicle-treated (p.o.), sodium acetate-treated (200 mg/kg), diabetic, and diabeticþ
sodium acetate-treated groups. Diabetes was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of
nicotinamide 110 mg/kg. The results showed that diabetic rats had, glucose dysregulation, elevated serum and cardiac triglyc eride, malondialdehyde, alanine aminotransferase, histone deacetylase, serum aspartate transaminase, cardiac low density
lipoprotein cholesterol (LDLc), glutathione/glutathione disulphide ratio (GSH/GSSG), reduced serum and cardiac high density
lipoprotein cholesterol (HDLc), and serum GSH/GSSG. Histological analysis revealed disrupted cardiac fiber in diabetic rats.
However, sodium acetate attenuated glucose dysregulation and improved serum and cardiac GSH/GSSG. Sodium acetate
normalized cardiac triglyceride accumulation, malondialdehyde, serum aspartate transaminase levels and prevented cardiac
tissue damage in diabetic rats. These effects were associated with suppressed histone deacetylase activity. Therefore,
sodium acetate attenuated but failed to normalize glucoregulation. Nevertheless, it ameliorated oxidative stress- and lipid
dysmetabolism-driven cardiovascular complications in diabetic rats by the suppression of histone deacetylase activity.
Description
This study provides evidence that STZ-NA induced diabetes mellitus is associated with cardiac triglyceride accumulation and
tissue disruption with corresponding increase in cardiac HDAC activity. However, sodium acetate suppresses cardiac HDAC activity and normalizes cardiac triglyceride and tissue integrity in diabetic rats. Therefore, the study suggests that sodium acetate is beneficial for
cardioprotection in diabetes mellitus.
Keywords
Glutathione, histone deacetylase, insulin resistance, oxidative stress, sodium acetate, type 2 diabetes
Citation
Olaniyi, K.S., Amusa, O.A., Areola, E.D., & Olatunji, L.A. (2020). Suppression of HDAC by sodium acetate rectifies cardiac metabolic disturbance in streptozotocin-nicotinamide-induced diabetic rats. Experimental Biology and Medicine, 245 (7), 667-676, Published by Society for Experimental Biology and Medicine. Available online at: Experimental Biology and Medicine - Volume 245, Number 7