LETROZOLE ATTENUATES CARDIOMETABOLIC RISK IN PLASMODIUM BERGHEI-INFECTED MICE

A. Abdulkareem, A. Babamale, Caleb Jesutomisin, Badmos-king Oluwabunmi, Dare Ibiwumi, L. Olatunji, U. Ugbomoiko
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Abstract

cardiovascular disease (CVD). We recently demonstrated letrozole’s cardioprotective effects in fructose-exposed male rats. Hence, in this study, we investigated the effect of a low-dose letrozole against cardiometabolic risk in Plasmodium berghei-infected female mice. Twenty female mice were randomly grouped into four (n=5/group): uninfected, infected, letrozole (0.24 mg/kg, p.o/day, without infection), and infected + letrozole. Weekly percentage parasitaemia was recorded. At the end of the 21-day exposure, blood and liver were collected and processed for biochemical analyses. P. berghei infection decreased serum estradiol level after 21-day infection and increased serum and liver levels of malondialdehyde, very low-density lipoprotein cholesterol, triglycerides, and triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) index. Similarly, P. berghei elevated serum uric acid and hepatic total cholesterol levels. Meanwhile, the administered dose of letrozole did not significantly affect serum estradiol but lowered lipid peroxidation, attenuated lipid alterations, and reduced serum uric acid level. We reveal that P. berghei-infection lowered serum estradiol and promoted cardiometabolic risk in female mice, while letrozole lowered parasitaemia and mitigated the associated cardiometabolic risk. Thus, this study is suggestive of letrozole’s potential as an adjuvant therapy for improved management of malaria-induced cardiometabolic complications. Further study is recommended to investigate the anti-malaria potency of letrozole, independent of gender.
来曲唑降低伯氏疟原虫感染小鼠的心脏代谢风险
心血管疾病(CVD)我们最近在暴露于果糖的雄性大鼠身上证明了来曲唑的心脏保护作用。因此,在本研究中,我们研究了低剂量来曲唑对伯氏疟原虫感染的雌性小鼠心脏代谢风险的影响。雌性小鼠20只,随机分为未感染、感染、来曲唑(0.24 mg/kg, p.o/day,未感染)、感染+来曲唑4组(n=5/组)。记录每周寄生虫率。在21天的暴露结束时,收集血液和肝脏并进行生化分析。感染柏氏螺旋体21天后血清雌二醇水平降低,血清和肝脏丙二醛、极低密度脂蛋白胆固醇、甘油三酯和甘油三酯/高密度脂蛋白胆固醇(TG/HDL-c)指数升高。同样地,柏氏弧菌升高血清尿酸和肝脏总胆固醇水平。同时,来曲唑给药剂量对血清雌二醇无显著影响,但能降低脂质过氧化,减轻脂质改变,降低血清尿酸水平。我们发现,伯氏疟原虫感染降低了雌性小鼠的血清雌二醇并增加了心脏代谢风险,而来曲唑降低了寄生虫血症并减轻了相关的心脏代谢风险。因此,这项研究提示来曲唑作为一种辅助治疗的潜力,可以改善疟疾引起的心脏代谢并发症的管理。建议进一步研究来曲唑的抗疟疾效力,不受性别的影响。
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