利用Wistar大鼠血液、胰腺和肠道基因表达研究杜氏刺蚜的毒理学研究

O. Ovuakporie-Uvo, M. Idu, Omotuyi I. Olaposi
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摘要

背景:毒性研究是在化学物质被纳入药物开发过程之前评估其副作用的相关研究。摘要:杜氏石笋(Desplatsia dewevrei)是一种稀有的森林植物,当地人认为它具有营养和治疗作用,但没有科学依据。因此,本研究旨在探讨短期和长期口服杜氏菌对Wistar大鼠的可能毒性。方法:Wistar大鼠每组4只(雌雄各2只),每日给药0、30、100、1000 mg/kg杜氏乳杆菌3、28 d。血液毒性和肝功能测试使用ERMA公司的自动化仪器完成。采用RT-PCR方法研究肠道葡萄糖转运蛋白4 (GLUT4)、葡萄糖转运蛋白2 (GLUT2)、胰高血糖素样肽-1 (GLP-1)、胰腺胰岛素、kcn5和l型电压门控钙通道基因(CACNAIA)的调控。结果:未见形态学和血液学毒性征象。肝功能检查显示,治疗组高密度脂蛋白(HDL-C)升高(100 mg/kg)。杜氏提取液的致死剂量(LD50)均在1000 mg/kg以上,在最高剂量下未见死亡。胰腺胰岛素的上调和肠道GLUT-2的下调表明该植物可能含有治疗成分。结论:短、长期给药是相对安全的。
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Toxicogenetic Studies of Desplatsia dewevrei using Gene Expression of Blood, Pancreatic, and Intestinal Genes in Wistar rats
Background: Toxicity studies are relevant in assessing the side effects of chemical substances before they are incorporated into the process of drug development. Introduction: Desplatsia dewevrei is a scarce forest species believed by natives to be nutritive and therapeutic, without scientific evidence though. Thus, this study was aimed at investigating the possible toxicity of shortand long-term oral administration of D. dewevrei using Wistar rats. Methods: 0, 30 100, and 1000 mg/kg of D. dewevrei were daily administered p.o for 3 and 28 days to Wistar rats consisting of four animals (two females, two males) per group. Hemotoxicity and liver function tests were done using automated machines from ERMA Inc. RT-PCR method was used to study the regulation of intestinal glucose transporter 4 (GLUT4), glucose transporter 2 (GLUT2), glucagon-like peptide-1 (GLP-1), pancreatic insulin, KCJN5, and L-type voltage-gated calcium channel genes (CACNAIA). Results: No morphological or hematological signs of toxicity were observed. Liver function test showed an elevated level of highdensity lipoprotein (HDL-C) in the treatment group (100 mg/kg). The lethal dose (LD50) of D. dewevrei extracts were above 1000 mg/kg as no mortality was observed at the highest regimen dose used. Up-regulation of pancreatic insulin and down-regulation of intestinal GLUT-2 suggest that the plant may contain therapeutic constituents. Conclusion: Shortor long-term administration of D. dewevrei is relatively safe.
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