Department of Chemistry, Faculty of Natural Sciences, University of Engineering and Technology, Lahore, Pakistan.
Beijing Laboratory of Biomedical Materials, Beijing Key Laboratory of Electrochemical Process and Technology of Materials, Beijing University of Chemical Technology, Beijing 100029, China.
Curr Med Chem. 2022;29(42):6422-6432. doi: 10.2174/0929867329666220203153051.
Bradykinin-potentiating peptides (BPPs) are snake venom peptides inhibiting the angiotensin-converting enzyme (ACE). ACE plays an important role in the regulation of blood pressure. BPPs lead to the development of ACE inhibitors for the treatment of hypertension.
The objective of the present work was to carry out a comprehensive comparative study of four synthesised snake venom BPPs in vivo.
Four synthesised snake venom BPPs were administered to rats via the intraperitoneal route for 15 days at a fixed dose. Lisinopril was used as a comparative standard. Thirty male albino rats were divided into six groups: A, B, C, D, E (lisinopril), and F (control). Group F was maintained as the control group and given only saline. After 15 days, blood samples and tissues were removed for the study of selective biochemical parameters and histomorphometric analysis. Statistical evaluation of all results was also performed.
The results indicated that peptide I, with the sequence ZSAPGNEAIPP, was highly toxic and adversely affected all the biochemical and histological parameters studied in this work. Peptide II (ZNWPHPQIPP) and peptide IV (ZQWAQGRAPHPP) showed lower toxicity. None of the BPPs raised the serum creatinine level and exhibited nephroprotective effects. Although lisinopril raised the creatinine level, it showed a protective role towards the pancreas and lungs in parallel.
The present work shows that although there is a high sequence similarity between the four BPPs, their in vivo activity varies. The sequences of peptide II and peptide IV can be used to improve the design of current ACE inhibitors used for hypertension treatment.
缓激肽增强肽（BPPs）是一种抑制血管紧张素转换酶（ACE）的蛇毒肽。ACE 在血压调节中起着重要作用。BPPs 导致 ACE 抑制剂的开发用于治疗高血压。
本研究旨在对四种合成蛇毒 BPPs 进行全面的体内比较研究。
四种合成蛇毒 BPPs 以固定剂量通过腹腔途径给予大鼠 15 天。赖诺普利用作比较标准。30 只雄性白化大鼠被分为六组：A、B、C、D、E（赖诺普利）和 F（对照）。F 组作为对照组，仅给予生理盐水。15 天后，采集血液样本和组织，用于研究选择性生化参数和组织形态计量学分析。还对所有结果进行了统计评估。
结果表明，序列为 ZSAPGNEAIPP 的肽 I 具有高度毒性，并对本工作研究的所有生化和组织学参数产生不利影响。肽 II（ZNWPHPQIPP）和肽 IV（ZQWAQGRAPHPP）的毒性较低。没有一种 BPPs 会升高血清肌酐水平，并表现出肾保护作用。虽然赖诺普利会升高肌酐水平，但它对胰腺和肺也表现出保护作用。
本研究表明，尽管这四种 BPPs 具有很高的序列相似性，但它们的体内活性却有所不同。肽 II 和肽 IV 的序列可用于改进当前用于治疗高血压的 ACE 抑制剂的设计。
