UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), UFR Sciences Exactes et Naturelles, Reims, France.
INSERM UMR1048 I2MC, Université Paul Sabatier, Toulouse, France.
J Cardiovasc Pharmacol. 2021 May 1;77(5):660-672. doi: 10.1097/FJC.0000000000001002.
Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of neuraminidases, such as neuraminidases 1 sialidase, may be useful for managing atherosclerosis. Several studies have reported promising effects of oseltamivir phosphate, a widely used anti-influenza sialidase inhibitor, on human cancer cells, inflammation, and insulin resistance. In this study, we evaluated the effects of oseltamivir phosphate on atherosclerosis and thrombosis and potential liver toxicity in LDLR-/- mice fed with high-fat diet. Our results showed that oseltamivir phosphate significantly decreased plasma levels of LDL cholesterol and elastin fragmentation in aorta. However, no effect was observed on both atherosclerotic plaque size in aortic roots and chemically induced thrombosis in carotid arteries. Importantly, oseltamivir phosphate administration had adverse effects on the liver of mice and significantly increased messenger RNA expression levels of F4/80, interleukin-1β, transforming growth factor-β1, matrix metalloproteinase-12, and collagen. Taken together, our findings suggest that oseltamivir phosphate has limited benefits on atherosclerosis and carotid thrombosis and may lead to adverse side effects on the liver with increased inflammation and fibrosis.
去唾液酸化作用由唾液酸酶或神经氨酸酶控制，与广泛的人类疾病密切相关，累积的数据表明，抑制神经氨酸酶，如神经氨酸酶 1 唾液酸酶，可能有助于管理动脉粥样硬化。有几项研究报告了磷酸奥司他韦（一种广泛使用的抗流感唾液酸酶抑制剂）对人类癌细胞、炎症和胰岛素抵抗的有希望的影响。在这项研究中，我们评估了磷酸奥司他韦对 LDLR-/- 小鼠高脂饮食喂养引起的动脉粥样硬化和血栓形成及潜在肝毒性的影响。我们的结果表明，磷酸奥司他韦可显著降低血浆 LDL 胆固醇和主动脉弹性蛋白片段水平。然而，在主动脉根部粥样斑块大小和颈动脉化学诱导血栓形成方面均无作用。重要的是，磷酸奥司他韦给药对小鼠肝脏有不良影响，并显著增加 F4/80、白细胞介素 1β、转化生长因子-β1、基质金属蛋白酶-12 和胶原的信使 RNA 表达水平。综上所述，我们的研究结果表明，磷酸奥司他韦对动脉粥样硬化和颈动脉血栓形成的益处有限，并且可能导致肝脏炎症和纤维化增加的不良反应。
