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Cytochrome P450s regulates aloperine-induced pathological changes in mouse liver and kidney.
Research in Veterinary Science ( IF 2.4 ) Pub Date : 2020-06-06 , DOI: 10.1016/j.rvsc.2020.06.005
Mingning Qiu 1 , Jie Liu 2 , Ping Feng 3 , Yongxia Su 2 , Rong Guo 2 , Fangyun Shi 2 , Shuai Wang 2 , Baoyu Zhao 2
Affiliation  

Aloperine is a major active component in Sophora alopecuroides L that plays diverse pharmacological properties. Recent studies have indicated the potential effect of aloperine against hypertension and cancers. However, possible toxicity of aloperine has not been carefully studied in vivo. The aim of this study was to assess the effect of intraperitoneal aloperine injection on mouse liver and kidney tissues and to investigate the role of CYP450 genes in aloperine-induced toxicity. 72 BALB/c mice were randomly divided into four groups: vehicle control group (normal saline), low-dose group (4 mg/kg), medium-dose group (8 mg/kg), and high-dose group (16 mg/kg). 18 mice in each group were intraperitoneally injected with aloperine daily for 4 weeks, and were then kept for another 1 or 4 weeks without aloperine treatment. Serum was colleted for analysis of serum biochemical indexes including ALT, AST, BUN and CRE. The liver and kidney were collected for analysis of histopathologic changes and CYP450 expression and activity. Vacuolization of cytoplasm in liver cells, swelling in kidney tubular cells, increased levels of ALT, AST, BUN, and CRE, and alteration in the expression and activity of CYP450 were observed in the high-dose group after 4 weeks of treatment. However, all aloperine-induced damages were recovered to a certain degree after maintained without aloperine for 1 week, and fully recovered after maintained without aloperine for 4 weeks. These findings suggested that aloperine regulated the expression of CYP450, which was possibly involved in aloperine-induced reversible toxicity in mouse liver and kidney tissues.



中文翻译:

细胞色素P450调节小鼠肝脏和肾脏中苦参碱引起的病理变化。

Aloperine是豆蔻L中的主要活性成分,具有多种药理特性。最近的研究表明,苦参碱具有抗高血压和抗癌作用。但是,尚未在体内仔细研究过苦参碱的可能毒性。这项研究的目的是评估腹膜内注射苦参碱对小鼠肝脏和肾脏组织的作用,并研究CYP450的作用。基因在苦参碱诱导的毒性中。将72只BALB / c小鼠随机分为四组:溶媒对照组(生理盐水),低剂量组(4 mg / kg),中剂量组(8 mg / kg)和高剂量组(16 mg) /公斤)。每组18只小鼠每天腹膜内注射苦参碱4周,然后再继续治疗1或4周而不进行苦参碱治疗。收集血清用于分析血清生化指标,包括ALT,AST,BUN和CRE。收集肝和肾用于分析组织病理学变化以及CYP450表达和活性。高剂量组在治疗4周后观察到肝细胞内的细胞质发生真空化,肾小管细胞肿胀,ALT,AST,BUN和CRE水平升高以及CYP450的表达和活性改变。然而,不用苦参碱维持1周后,所有由苦参碱引起的损害都得到了一定程度的恢复,而不用苦参碱维持4周后,其损伤完全恢复了。这些发现表明,苦参碱调节CYP450的表达,这可能与苦参碱对小鼠肝脏和肾脏组织的可逆毒性有关。

更新日期:2020-06-06
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