Aisha Munawar*, Fakhar Zaman, Muhammad Waqas Ishaq, Khwaja Ali Hassan, Saima Masood, Zahid Ali, Khalid Abdul Majeed, Ahmed Akrem, Syed Abid Ali and Christian Betzel Pages 6422 - 6432 ( 11 )
Background: 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.
Objective: The objective of the present work was to carry out a comprehensive comparative study of four synthesised snake venom BPPs in vivo.
Methods: 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.
Results: 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.
Conclusion: 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.
Snake venom bradykinin-potentiating peptides, lisinopril, creatinine, seminiferous tubules, liver histomorphometry, ACE.