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.

中文翻译：

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氮卓斯汀是一种有效的抗组胺剂，作为糖尿病高脂血症大鼠模型主动脉钙化的降血脂和调节剂

摘要

目标

我们的研究旨在阐明抗组胺药氮卓斯汀对糖尿病高脂血症（DH）大鼠主动脉钙化的影响及其潜在的分子机制。

方法

将 24 只雄性白化 ​​Wistar 大鼠分为四组。一组接受正常啮齿动物食物（正常组），而其他组则出现糖尿病和高脂血症；一组未接受药物治疗并作为阳性对照，而另外两组接受氮卓斯汀 (4 mg/kg) 或 10-脱氢姜二酮 (10 mg/kg) 口服和每天服用 8 周。

结果

与对照组相比，氮卓斯汀显着降低血糖、HbA1c 和血清 ALP、OCN，下调 apo B，改善血脂（LDL-c 降低和 HDL-c 升高），减轻钙沉积和主动脉钙化。10-DHGD显示出相对较低的效果。

结论

氮卓斯汀的抗钙化作用可能与 apo A (HDL-c) 的上调和 apo B mRNA 表达的下调有关，确实是主动脉钙化的良好调节剂。

影响陈述

许多研究表明，高密度脂蛋白胆固醇 (HDL-c) 与动脉粥样硬化斑块进展呈负相关，可降低心血管疾病风险。已经报道了 HDL-c 的抗钙化作用，因此靶向这种脂蛋白可能是控制血管钙化的一种有价值的方法。氮卓斯汀是一种选择性 H1 拮抗剂，经鉴定可增加载脂蛋白 A 的 mRNA 表达。这鼓励我们研究氮卓斯汀对 DH 大鼠脂质谱和主动脉钙化标志物的影响。我们的研究结果表明，氮卓斯汀改善了主动脉钙化并增加了 apoA 表达以及 apo B 的下降。这可能代表了潜在的机制，而组织病理学研究结果为收集的生化数据提供了重要支持。