Letrozole Attenuates Cardiometabolic Risk in Plasmodium Berghei-Infected Mice

Abstract

Malaria is associated with cardiometabolic disorders, promoting the risk of 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.