一种生物活性化合物混合物对健康Wistar大鼠急性和亚急性毒理学评价。

IF 1.9 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Thushara Indika Sampath, Susanthi Jayasinghe, Anoja Priyadarshani Attanayake, Veranja Karunaratne
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引用次数: 0

摘要

随着人们对生物活性化合物的兴趣日益浓厚,在将其开发为治疗性药物之前,必须彻底了解其体内安全性。本研究旨在评估一种由garcinol、胡椒碱、油酸丁酯、胡椒碱和双氰胺组成的复合混合物在健康Wistar大鼠体内的急性和亚急性毒理学效应,其摩尔质量比为9:33:1:4:1,剂量为10 mg kg-1、25 mg kg-1和50 mg kg-1,遵循经济合作与发展组织的指导方针。给予单次口服剂量(10 mg kg-1、25 mg kg-1和50 mg kg-1),并在随后的14天内密切观察大鼠。此外,以相同的三种剂量给药Wistar大鼠,连续28天。在整个14天内,三种剂量的复合混合物均未产生死亡或异常行为变化。血液学指标、谷丙转氨酶、天冬氨酸转氨酶、碱性磷酸酶、肌酐等生化指标均无明显变化(p < 0.05)。组织病理学分析显示,肝脏、肾脏、心脏、脾脏、胃、小肠和肺组织的苏木精和伊红染色切片未见治疗相关变化。总之,通过对苏木精和伊红染色组织切片的生化(肝酶、肾功能测试)、血液学(全血细胞计数分析)和组织学评估,发现健康Wistar大鼠口服10 mg kg-1、25 mg kg-1和50 mg kg-1复方制剂28天是安全的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acute and sub-acute toxicological evaluation of a bioactive compound mixture in healthy Wistar rats.

The increasing interest in bioactive compounds necessitates a thorough understanding of their in vivo safety profiles before they are developed as therapeutic drug leads. The present study aimed to evaluate acute and sub-acute toxicological effects of a compound mixture composed of garcinol, piperine, butyl oleate, pipnoohine, and bismurrayanimbine, combined in a molar mass ratio of 9:33:1:4:1 at the doses of 10 mg kg-1, 25 mg kg-1, and 50 mg kg-1 in healthy Wistar rats, following Organization for Economic Co-operation and Development guidelines. A single oral dose of the compound mixture (10 mg kg-1, 25 mg kg-1, and 50 mg kg-1) was administered, and the rats were closely observed over a subsequent 14-day period. Further, the compound mixture was administered orally at the same three doses to Wistar rats continuously for 28 days. The compound mixture at the three doses did not produce mortality or abnormal behavioral changes throughout the 14 days. No significant alterations in hematological parameters or biochemical markers such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and creatinine (p > 0.05) were observed. Histopathological analysis revealed no treatment-related changes in the hematoxylin and eosin-stained sections of the liver, kidney, heart, spleen, stomach, small intestine, and lung tissues. In conclusion, the oral administration of compound mixture at 10 mg kg-1, 25 mg kg-1, and 50 mg kg-1 for 28 days was found to be safe in healthy Wistar rats via biochemical (liver enzymes, kidney function tests), hematological (full blood count analysis), and histological assessments of hematoxylin and eosin-stained tissue sections.

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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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