High-fat diet promotes coagulation and endothelial activation in Sprague Dawley rats: Short-term effects of combined oral contraceptives

Oyesanmi A. Fabunmi , Phiwayinkosi V. Dludla , Bongani B. Nkambule
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Abstract

Background

Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats.

Methods

Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200 g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks.

Results

Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p < 0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p > 0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals.

Conclusion

HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. However, additional studies are required to confirm these findings, especially long-term effects of this treatment within the cardiac tissues or endothelial cells of these animals in certain conditions relating to postmenopausal state.

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高脂饮食会促进 Sprague Dawley 大鼠的凝血和内皮活化:联合口服避孕药的短期效应
背景复合口服避孕药(COC)的使用与血栓事件风险的增加有关。这凸显了评估 COC 对促进高脂饮食(HFD)喂养的 Sprague Dawley 大鼠凝血和内皮活化的影响的重要性。方法对 20 只体重在 150 至 200 克之间的 5 周大雌性 Sprague Dawley 大鼠进行为期 8 周的低脂饮食和高脂饮食喂养,以确定其对基本代谢状态、止血状况、血液动力学参数(血压和心率)以及选定的凝血生物标志物(组织因子和 D-二聚体)和内皮活化生物标志物(冯-威廉因子和一氧化氮)的影响。结果我们的研究结果表明,与 LFD 组相比,HFD 组动物除了体重增加外,还伴有高血糖、平均动脉压升高和一氧化氮水平降低(p < 0.05)。有趣的是,连续 6 周服用大剂量 COC 并未显著改变动脉粥样硬化血栓标志物(p > 0.05)。结论高脂血症大鼠在进食过程中会同时释放促凝血剂和内皮活化标志物,导致止血失衡和内皮功能障碍。用 COC 进行短期治疗不会对这些高纤维食物喂养的大鼠产生不利影响。尽管就临床相关性而言,我们的研究结果表明,与 COC 相关的心血管疾病风险可能取决于使用的剂量和持续时间等因素,尤其是在某些情况下。不过,还需要进行更多的研究来证实这些发现,特别是在绝经后的某些情况下,这种疗法对这些动物的心脏组织或内皮细胞的长期影响。
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