Adverse cardiac events of hypercholesterolemia are enhanced by sitagliptin in sprague dawley rats.

IF 3.9 2区医学 Q2 NUTRITION & DIETETICS Nutrition & Metabolism Pub Date : 2024-07-30 DOI:10.1186/s12986-024-00817-9

Henry A Palfrey, Avinash Kumar, Rashmi Pathak, Kirsten P Stone, Thomas W Gettys, Subramanyam N Murthy

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Abstract

Background: Cardiovascular disease (CVD) affects millions worldwide and is the leading cause of death among non-communicable diseases. Western diets typically comprise of meat and dairy products, both of which are rich in cholesterol (Cho) and methionine (Met), two well-known compounds with atherogenic capabilities. Despite their individual effects, literature on a dietary combination of the two in the context of CVD are limited. Therefore, studies on the combined effects of Cho and Met were carried out using male Sprague Dawley rats. An additional interest was to investigate the cardioprotective potential of sitagliptin, an anti-type 2 diabetic drug. We hypothesized that feeding a dietary combination of Cho and Met would result in adverse cardiac effects and would be attenuated upon administration of sitagliptin.

Methods: Adult male Sprague-Dawley rats were fed either a control (Con), high Met (1.5%), high Cho (2.0%), or high Met (1.5%) + high Cho (2.0%) diet for 35 days. They were orally gavaged with an aqueous preparation of sitagliptin (100 mg/kg/d) or vehicle (water) from day 10 through 35. On day 36, rats were euthanized, and tissues were collected for analysis.

Results: Histopathological evaluation revealed a reduction in myocardial striations and increased collagen deposition in hypercholesterolemia (HChol), responses that became exacerbated upon sitagliptin administration. Cardiac pro-inflammatory and pro-fibrotic responses were adversely impacted in similar fashion. The addition of Met to Cho (MC) attenuated all adverse structural and biochemical responses, with or without sitagliptin.

Conclusions: Adverse cardiac outcomes in HChol were enhanced by the administration of sitagliptin, and such effects were alleviated by Met. Our findings could be significant for understanding or revisiting the risk-benefit evaluation of sitagliptin in type 2 diabetics, and especially those who are known to consume atherogenic diets.

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西他列汀会加重高胆固醇血症对 sprague dawley 大鼠心脏的不良影响。

背景：心血管疾病（CVD）影响着全球数百万人，是非传染性疾病中的首要死因。西方饮食通常包括肉类和乳制品，这两种食物都富含胆固醇（Cho）和蛋氨酸（Met），这是两种众所周知的具有致动脉粥样硬化能力的化合物。尽管这两种物质对心血管疾病有单独的影响，但有关这两种物质的饮食组合的文献却很有限。因此，我们使用雄性 Sprague Dawley 大鼠对 Cho 和 Met 的联合作用进行了研究。我们的另一个兴趣点是研究西格列汀（一种抗 2 型糖尿病药物）的心脏保护潜力。我们假设，喂食 Cho 和 Met 的饮食组合会对心脏产生不良影响，而在服用西他列汀后，这种影响会减弱：成年雄性 Sprague-Dawley 大鼠连续 35 天喂食对照组（Con）、高 Met（1.5%）、高 Cho（2.0%）或高 Met（1.5%）+ 高 Cho（2.0%）饮食。从第 10 天到第 35 天，给大鼠口服西格列汀水溶液制剂（100 毫克/千克/天）或载体（水）。第 36 天，大鼠被安乐死，并收集组织进行分析：组织病理学评估显示，高胆固醇血症（HChol）大鼠的心肌条纹减少，胶原沉积增加，服用西格列汀后这些反应加剧。心脏促炎和促纤维化反应也受到类似的不利影响。无论是否服用西格列汀，在Cho（MC）中添加Met都会减轻所有不良的结构和生化反应：结论：服用西他列汀会加重高胆固醇血症患者的心脏不良反应，而 Met 可减轻这种影响。我们的研究结果对于理解或重新评估西格列汀对2型糖尿病患者，尤其是已知食用致动脉粥样硬化饮食的患者的风险-效益具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nutrition & Metabolism 医学-营养学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects. The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases. Key areas we wish to encourage submissions from include: -how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes; -the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components; -how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved; -how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.