Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Chemistry Department (Biochemistry Division), Faculty of science, Zagazig University, Zagazig, Egypt.
J Pharm Pharmacol. 2020 Dec;72(12):1812-1821. doi: 10.1111/jphp.13363. Epub 2020 Sep 3.
The present study aimed mainly to demonstrate the effect of the antihistamine azelastine (AZ) and Angiotensin receptor blocker ( ARB), represented by losartan (LOS) either alone or in combined form on certain metabolic aspects, endothelial dysfunction and platelets activation markers in diabetic hyperlipidemic rat model.
Rats were randomly classified to five groups: One group fed normal chow diet (NC). Four groups received alloxan and CCT-diet. One group received no treatment (DHC while the other three groups received AZ, LOS and their combination form, respectively for 8 weeks. Serum and tissue samples were collected for biochemical and histological evaluations.
DHC rats demonstrated significant hyperglycaemia, dyslipidemia, disturbances in endothelial and platelet activation markers. AZ or LOS administration demonstrated hypoglycaemic and hypolipidemic effects. VCAM-1 and sE-selectin (Endothelial function markers) along with CD63 (Platelet activation marker) showed significant decrease as compared to control group. AZ administration exerted little prominent effects than that of LOS, while their combination demonstrated remarkable changes compared to monotherapy. Histopathological findings were in agreement to certain extent with the biomarkers results.
Both drug categories may be expressed as suitable therapeutic tools for atherosclerotic complications either alone or along with other hypolipidemic drugs.
本研究主要旨在展示抗组胺药氮卓斯汀(AZ)和血管紧张素受体阻滞剂(ARB),以氯沙坦(LOS)为代表,单独或联合应用于糖尿病高脂血症大鼠模型对某些代谢方面、内皮功能障碍和血小板活化标志物的影响。
将大鼠随机分为五组:一组给予正常饲料(NC)。四组给予链脲佐菌素和 CCT 饮食。一组未接受任何治疗(DHC),而其他三组分别给予 AZ、LOS 及其联合制剂,持续 8 周。采集血清和组织样本进行生化和组织学评估。
DHC 大鼠表现出明显的高血糖、血脂异常、内皮和血小板活化标志物紊乱。AZ 或 LOS 的给药表现出降血糖和降血脂作用。与对照组相比,VCAM-1 和 sE-选择素(内皮功能标志物)以及 CD63(血小板活化标志物)显著降低。AZ 给药的效果不如 LOS 明显,而两者联合治疗则显示出显著的变化。组织病理学发现与生物标志物结果在一定程度上相符。
这两类药物单独或联合其他降脂药物,均可作为治疗动脉粥样硬化并发症的合适治疗工具。