Short-term low-dose aspirin attenuates metabolic and endothelial dysfunction, as well as prothrombotic and inflammatory responses, orchestrated by combined oral contraceptive exposure in female rats.

Background Atherothrombosis is a chronic, multifactorial, and progressive disease responsible for a significant number of deaths globally. It involves interactions between endothelial dysfunction, coagulation activation, platelet activity, and fibrin turnover. Combined oral contraceptives (COCs) may influence these pathways, potentially altering thrombotic risk. The aim was to assess the impact of COC administration on metabolic status and the risk of atherothrombotic disorders in young female rats, beyond evaluating the therapeutic effects of short-term low-dose aspirin (LDA) treatment. Methods Thirty (n=30) five-week-old female Sprague Dawley rats were given low-dose COC (LCOC) or a high-dose COC (HCOC) for six weeks before treatment with LDA for another four weeks. These rats were compared with those given only LCOC or HCOC without LDA treatment. Whereas rats that received distilled water (as a vehicle) and LDA only served as controls. Body weight and metabolic status were measured weekly. Parameters related to glucose regulation, lipid profiles, inflammatory cytokines, haematological indices, coagulation, and endothelial dysfunction were evaluated at the end of the experiment. Results Rats exposed to HCOC exhibited abnormal metabolic and lipid profiles, including impaired glucose tolerance, accompanied by significantly higher insulin (p < 0.001), triglycerides and very low-density lipoprotein levels (p = 0.004) when compared with control groups. The HCOC treatment was also associated with elevated platelet count (p = 0.02) and markers of inflammation and endothelial dysfunction, including IL-6 (p < 0.05), TNF-alpha (p < 0.05), MCP-1 (p < 0.001), TF (p < 0.001), D-dimer (p < 0.001), von Willebrand factor (p < 0.05), and low nitric oxide (p < 0.001) when compared with control groups. Notably, SBP and MAP (p = 0.02) were also significantly higher in these animals, suggesting an increased atherothrombotic risk in response to HCOC when compared to control groups. Interestingly, short-term LDA attenuate atherothrombotic risk by improving metabolic status, alleviating inflammation, and lowering the markers of coagulation and endothelial dysfunction in rats exposed to HCOC. Conclusion Short-term LDA reduces the risk of atherothrombotic disorders by attenuating biomarker level associated with metabolic dysregulation, endothelial dysfunction, proinflammation, and hypercoagulation in female rats exposed to high-dose COC. However, additional experimental studies are required to explore the mechanistic interaction between LDA and COC at the cellular level.