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揭示青蒿琥酯对小鼠模型中新出现的人畜共患病感染的治疗潜力。

Unrevealing the therapeutic potential of artesunate against emerging zoonotic infection in the murine model.

作者信息

Fazilani Saqib Ali, An Wei, Li Sihong, Hassan Mohammad Farooque, Ishfaq Muhammad, Lakho Shakeel Ahmed, Farooque Muhammad, Shoaib Muhammad, Zhang Xiuying

机构信息

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development. Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Department of Veterinary Pharmacology and Toxicology, Faculty of Biosciences, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand, Pakistan.

出版信息

Front Vet Sci. 2024 May 9;11:1383291. doi: 10.3389/fvets.2024.1383291. eCollection 2024.

Abstract

Babesiosis, a zoonotic blood protozoal disease, threatens humans and animals and is difficult to treat due to growing antimicrobial resistance. The study aimed to investigate the therapeutic efficacy of artesunate (AS), a well-known derivative of artemisinin, against () using a murine infection model. Male BALB/c mice (6 weeks old; 15 per group) were chosen and randomly divided into 1) the control group, 2) group, and 3) the  + artesunate treatment groups. AS treatment at 2 mg/kg, 4 mg/kg, and 8 mg/kg of body weight significantly ( < 0.05) reduced the load in blood smears in a dose-dependent manner. Additionally, AS treatment mitigated the decrease in body weight and restored the normal state of the liver and spleen viscera index compared to the -infected group after 28 days. Hematological analysis revealed significant increases in RBC, WBC, and PLT counts post-AS treatment compared to the -infected group. Furthermore, AS administration resulted in significant reductions in total protein, bilirubin, ALT, AST, and ALP levels, along with reduced liver and spleen inflammation and lesions as observed through histopathological analysis. AS also elicited dose-dependent changes in mRNA and protein expression levels of apoptotic, proinflammatory, and anti-inflammatory cytokines in the liver compared to the control and -infected groups. Immunolabeling revealed decreased expression of apoptotic and inflammation-related proteins in AS-treated hepatic cytoplasm compared to the -infected group. AS also in dose-dependent manner decreased apoptotic protein and increased Bcl-2. Overall, these findings underscore the potential of AS as an anti-parasitic candidate in combating pathogenesis in an infection model, suggesting its promise for clinical trials as a treatment for babesiosis.

摘要

巴贝斯虫病是一种人畜共患的血液原生动物疾病,由于抗菌药物耐药性不断增加,它对人类和动物构成威胁且难以治疗。本研究旨在使用小鼠感染模型研究青蒿琥酯(AS)(一种著名的青蒿素衍生物)对()的治疗效果。选用雄性BALB/c小鼠(6周龄;每组15只),随机分为1)对照组、2)()组和3)()+青蒿琥酯治疗组。以2mg/kg、4mg/kg和8mg/kg体重的剂量进行青蒿琥酯治疗,显著(P<0.05)以剂量依赖的方式降低了血涂片中的()负荷。此外,与()感染组相比,青蒿琥酯治疗在28天后减轻了体重下降,并恢复了肝脏和脾脏脏器指数的正常状态。血液学分析显示,与()感染组相比,青蒿琥酯治疗后红细胞、白细胞和血小板计数显著增加。此外,通过组织病理学分析观察到,青蒿琥酯给药导致总蛋白、胆红素、谷丙转氨酶、谷草转氨酶和碱性磷酸酶水平显著降低,同时肝脏和脾脏炎症及病变减轻。与对照组和()感染组相比,青蒿琥酯还引起肝脏中凋亡、促炎和抗炎细胞因子的mRNA和蛋白质表达水平呈剂量依赖性变化。免疫标记显示,与()感染组相比,青蒿琥酯处理的肝细胞质中凋亡和炎症相关蛋白的表达降低。青蒿琥酯还以剂量依赖的方式降低凋亡蛋白并增加Bcl-2。总体而言,这些发现强调了青蒿琥酯作为抗寄生虫候选药物在()感染模型中对抗()发病机制的潜力,表明其有望作为巴贝斯虫病的治疗药物进行临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9bd/11111996/92d6ce92fd10/fvets-11-1383291-g001.jpg

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