Effect of 3,4-dihydroxyacetophenone on endothelial dysfunction in obese rats

Abstract

Context: 3,4-Dihydroxyacetophenone (DHAP) has been reported to possess cardiovascular pharmacological effects.Objective: This study was designed to determine whether DHAP could improve endothelial function in obese rats.Materials and methods: Wistar rats were randomly divided into control, obesity, and DHAP groups and fed a normal, high-fat, and high-fat plus DHAP (10 mg kg−1 d−1) diet, respectively, for 8 weeks. Endothelial-dependent vasodilatation was assessed. Endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells were determined. Nuclear transcription factor kappa B (NF-κB) expression and superoxide production in aorta were evaluated.Results: DHAP treatment significantly decreased plasma triglycerides (0.94 ± 0.31 mmol/l versus 1.36 ± 0.29 mmol/l, p < 0.05) and free fatty acids (0.53 ± 0.15 mmol/l versus 0.99 ± 0.24 mmol/l, p < 0.05), reduced serum tumor necrosis factor α (35.56 ± 9.28 pg/ml versus 68.3 ± 10.24 pg/ml, p < 0.05) and malondialdehyde (2.94 ± 0.58 pg/ml versus 6.45 ± 0.70 pg/ml, p < 0.05), and increased serum adiponectin levels (164.5 ± 34.5 μg/l versus 84.5 ± 20.4 μg/l, p < 0.05). DHAP enhanced endothelial-dependent vasodilatation and improved endothelial function in obese rats (p < 0.05). eNOS activity and NO production in endothelial cells significantly decreased and NF-κB activation and superoxide production in aorta significantly increased in obese rats compared with the control group (p < 0.05). However, DHAP treatment significantly up-regulated the eNOS–NO pathway and decreased NF-κB activation and superoxide production (p < 0.05).Conclusion: DHAP improved endothelial function in obese rats. This beneficial effect may be associated with up-regulation of the eNOS–NO pathway by improving lipid metabolism and reducing oxidative stress and inflammation activity.