Effect of Etanercept on Plasmodium yoelii MDR-Induced Liver Lipid Infiltration

B. Chauhan, Sarika Gunjan, S. K. Singh, S. Pandey, R. Tripathi
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Abstract

The lipid is a vital metabolic and structural component of the malaria parasite. Malaria parasite-induced liver lipid deposits undergo peroxidation, which ultimately causes tissue damage and histopathological changes, which further lead to many complications. Therefore, it is essential to focus on the factors responsible for this stimulated lipid accumulation during malaria infection. In the present study, we have correlated the significant increase in serum TNF-α and liver triglyceride during Plasmodium yoelii MDR infection in mice. In order to explore the role of TNF-α in inducing lipid accumulation in the liver during malaria infection, we have used a competitive TNF-α inhibitor Etanercept, for the treatment of Plasmodium yoelii MDR (Py MDR) infected mice and found that Etanercept displayed up to a three-fold inhibition of the liver triglyceride level in Py MDR infected mice. These results were also confirmed by triglyceride specific oil red O staining of liver sections. In addition, all the treatment groups also showed inhibition in the level of serum TNF-α and the liver malondialdehyde (MDA), a byproduct of lipid peroxidation. Our study thus concludes that Etanercept significantly reduces Plasmodium-induced liver triglyceride and further saves the host liver from malaria-induced lipid infiltration and liver damage. Therefore, treatment with Etanercept, along with a standard antimalarial, may prove a better therapy for the disease.
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依那西普对杨氏疟原虫耐多药肝脂浸润的影响
脂质是疟原虫重要的代谢和结构成分。疟疾寄生虫诱导的肝脏脂质沉积发生过氧化,最终导致组织损伤和组织病理改变,进而导致许多并发症。因此,重点关注疟疾感染期间引起脂质积累的因素至关重要。在本研究中,我们发现小鼠在约尔疟原虫耐多药感染期间血清TNF-α和肝脏甘油三酯显著升高。为了探索TNF-α在疟疾感染期间诱导肝脏脂质积累中的作用,我们使用了一种竞争性TNF-α抑制剂依那西普,用于治疗pymdr感染小鼠,发现依那西普对pymdr感染小鼠的肝脏甘油三酯水平有高达三倍的抑制作用。肝脏切片的甘油三酯特异性油红O染色也证实了这些结果。此外,各治疗组均抑制血清TNF-α和肝脏丙二醛(脂质过氧化副产物)水平。因此,我们的研究表明依那西普可以显著降低疟原虫诱导的肝脏甘油三酯,进一步保护宿主肝脏免受疟疾诱导的脂质浸润和肝脏损伤。因此,使用依那西普和标准的抗疟药物治疗可能是治疗疟疾的更好方法。
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