Acute Toxicity Study of Recombinant Exendin-4 in Swiss Albino Mice

Gowthami Vangala*¹, Sumasri Guntupalli², Venugopalaiah Penabaka³, Pasupuleti Naresh^3
1Department of Biotechnology, Virchow Biotech Private Limited, Hyderabad, Telangana, India
²Department of Pharmacology, Shri Vishnu College of Pharmacy, Andhra Pradesh, India
³Department of Pharmaceutics, Ratnam Institute of Pharmacy, SPSR Nellore, Andhra Pradesh, India

A B S T R A C T
Recombinant Exendin-4 is a 39 amino acid peptide which exhibits sequence identity over 30 amino acids with mammalian glucagon like peptide-1 (GLP-1) and shares many of the gluco-regulatory actions observed with GLP-1. It enhances glucose-dependent insulin secretion in the pancreatic beta-cells by suppressing inappropriately elevated glucagon secretion, and slows down the process of gastric emptying in the gut. Unlike GLP-1, Recombinant Exendin-4 exhibit extended kinetics due to its resistance to proteolytic degradation by dipeptidyl peptidase IV (DPP-IV) and has higher potency for in vivo glucose lowering effect. The present study was performed to investigate the single-dose toxicity of recombinant Exendin-4 in Swiss Albino Mice. The test compound was injected at 10 times the intended therapeutic dose for once in 10 (5M+5F) mice intravenously (IV) and in another group of 10 (5M+5F) mice it was injected subcutaneously. Animals were observed for a period of 14 days for mortality and morbidity. In overall study, we found that the single high dose administration of recombinant Exendin-4 did not exert any toxic effects in Swiss Albino Mice until the end of the observation period. No treatment related changes were detected for body weight, feed intake, haematology, clinical chemistry, and organ weight. There were no adverse clinical signs indicative of an anaphylactic response and no mortality and morbidity were observed during the experimental period.
Keywords: Exendin-4, Amino acid peptide, GLP-1, DPP-IV, Swiss Albino Mice, Haematology.