Azelastine a potent antihistamine agent, as hypolipidemic and modulator for aortic calcification in diabetic hyperlipidemic rats model

Abstract

Aim

Our study aimed to illustrate the effect of the antihistaminic drug azelastine on aortic calcification in diabetic hyperlipidemic (DH) rats along with the underlying molecular mechanism.

Methods

Twenty-four male albino Wistar rats were categorised into four groups. One group received normal rodent chow (normal group), while the other groups were rendered diabetic and hyperlipidemic; one received no drugs and served as a positive control while the other two groups received either azelastine (4 mg/kg) or 10-dehydrogingerdione (10 mg/kg) orally and daily for 8 weeks.

Results

Azelastine significantly reduced blood glucose, HbA1c and serum ALP, OCN, downregulated apo B, improved the lipid profile (LDL-c decrease and HDL-c increase), attenuated calcium deposition and aortic calcification as compared to control group. 10-DHGD showed comparatively lower effect.

Conclusion

Anti-calcifying effect of azelastine might be related to upregulation of apo A (HDL-c) and downregulation of apo B mRNA expression indeed good modulator of aortic calcification.

Impact Statement

Many studies have indicated that high-density lipoprotein-cholesterol (HDL-c) is inversely correlated with atherosclerotic plaque progression and could reduce cardiovascular disease risk. An anti-calcifying effect of HDL-c has been reported and targeting this lipoprotein may therefore be a valuable approach to vascular calcification control. Azelastine is a selective H1 antagonist that was identified to increase mRNA expression of apolipoprotein A. This encouraged us to investigate the effect of azelastine on lipid profile and markers of aortic calcification in DH rats. Our findings showed that azelastine ameliorated aortic calcification and increased apoA expression along with a decline in apo B. This may represent the underlying mechanism while the histopathological findings offered a significant support to the collected biochemical data.

Keywords:

• Azelastine
• 10-dehydrogingerdione
• aortic calcification
• osteocalcin
• alkaline phosphatase
• HDL-c

Acknowledgements

The authors acknowledge the efforts of Dr. AbdElmoniem Aly, Professor of Pathology, Faculty of Veterinary Medicine, Zagazig University, during the histopathology work. The authors also acknowledge the help of Dr. Mohamed Shawky, Lecturer of Biochemistry, Faculty of Pharmacy, Horus University-Egypt, during the preparation of the manuscript.

Disclosure statement

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Authors’ contribution

MME conceived the idea, designed and supervised the study; GME wrote the article, - edited and revised the draft; MM conducted most of the experiments; NZ conducted the statistical analysis. All authors contributed to the data analysis and approved the final version of the manuscript.