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The alleviative efficacy of sildenafil and chrysin against zinc oxide nanoparticles-provoked hepatic and blood toxicity: role of MyD88/NF-κB1/TNF-α pathway
Beni-Suef University Journal of Basic and Applied Sciences Pub Date : 2023-11-08 , DOI: 10.1186/s43088-023-00440-2
Mahitab M. Nageeb , Marwa Abdel-Moniem Amer , Doaa M. Hendawy , Sabah Mohamed Hanafy , Maha Saad Elmenshawi , Gena M. Elmakromy , Dena Mohamed Naguib Abdel Moawed

Zinc oxide nanoparticles are nanoparticles of metal oxide with semiconductor properties and proved many noxious effects on the mammalian cell. Sildenafil, a phosphodiesterase inhibitor, and chrysin, one of the flavonoids, proved to have anti-inflammatory and anti-oxidative stress effects. 48 rats were grouped into 8 groups equally. 1. (Control group) received normal diet and NaOH was added to water, 2. (chrysin group): 250 mg/kg, orally for 10 days, 3. (sildenafil group): 40 mg/kg, orally for 14 days, 4. (ZnO-NPs group): 200 mg/kg, intraperitoneal for 10 days, 5. (ZnO-NPs + chrysin as a prophylactic agent): given in the same previous doses and durations consecutively, 6. (ZnO-NPs + chrysin as a curative agent): given in the same previous doses and durations with chrysin given after ZnO-NPs administration for 10 days, 7. (ZnO-NPs + sildenafil as a curative agent): given in the same previous doses and durations with sildenafil given after ZnO-NPs administration for 10 days, and 8. (Combined treatment group chrysin + sildenafil) as combined treatment were given in the same previous doses and durations after ZnO-NPs administration for 10 days. Blood and samples from tissues were withdrawn for histopathological, biochemical studies, and comet assay at the end of the experiment. Sildenafil and chrysin proved to protect from hepatotoxicity and hematotoxicity induced by zinc oxide nanoparticles as they lessened aspartate transaminase, alanine transferase, and alkaline phosphatase levels. They also reduced the oxidative stress enzyme levels. Gene expression of myeloid differentiation factor 88, nuclear factor kappa B1, tumor necrosis factor, and DNA damage decreased with treatment. Also, there was an improvement in the histopathological picture of the liver seen with treatment. Concurrent administration of sildenafil and chrysin revealed much better improvement than either drug used alone. Chrysin and sildenafil have ameliorative effects against ZnO-NPs-induced hepatotoxicity and hematotoxicity, their protective effect is either preventive with chrysin or curative with chrysin and sildenafil.

中文翻译:

西地那非和白杨素对氧化锌纳米颗粒引起的肝脏和血液毒性的缓解作用:MyD88/NF-κB1/TNF-α通路的作用

氧化锌纳米颗粒是具有半导体特性的金属氧化物纳米颗粒,并被证明对哺乳动物细胞有许多有害作用。西地那非(一种磷酸二酯酶抑制剂)和白杨素(黄酮类化合物之一)已被证明具有抗炎和抗氧化应激作用。将48只大鼠平均分为8组。1.(对照组)正常饮食,水中加入NaOH,2.(白杨素组):250mg/kg,口服10天,3.(西地那非组):40mg/kg,口服14天, 4.(ZnO-NPs组):200mg/kg,腹腔注射10天,5.(ZnO-NPs+白杨素作为预防剂):以相同的先前剂量和持续时间连续给药,6.(ZnO-NPs+白杨素作为预防剂):连续给予白杨素作为治疗剂):与 ZnO-NPs 给药 10 天后给予白杨素相同的剂量和持续时间,7。(ZnO-NPs + 西地那非作为治疗剂):与之前相同的剂量和持续时间ZnO-NPs给药10天后给予西地那非,8.(联合治疗组白杨素+西地那非)作为联合治疗,ZnO-NPs给药10天后以与之前相同的剂量和持续时间给予。实验结束时,抽取血液和组织样本进行组织病理学、生化研究和彗星测定。西地那非和白杨素被证明可以防止氧化锌纳米粒子引起的肝毒性和血液毒性,因为它们降低了天冬氨酸转氨酶、丙氨酸转移酶和碱性磷酸酶的水平。他们还降低了氧化应激酶的水平。治疗后,骨髓分化因子 88、核因子 kappa B1、肿瘤坏死因子和 DNA 损伤的基因表达降低。此外,治疗后肝脏的组织病理学图像也有所改善。同时服用西地那非和白杨素比单独使用任何一种药物都有更好的改善。白杨素和西地那非对ZnO-NPs引起的肝毒性和血液毒性具有改善作用,其保护作用既可以是白杨素的预防作用,也可以是白杨素和西地那非的治疗作用。
更新日期:2023-11-08
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