Toxicology Assessment of a Dual-Function Peptide 5rolGLP-HV in Mice.

Ni, Zaizhong; Wang, Bin; Ma, Xiaofeng; Duan, Huikun; Jiang, Pingzhe; Li, Xiaodan; Wei, Qian; Ji, Xiangzhen; Li, Minggang

5rolGLP-HV had an ideal therapeutic potential in the prevention of hyperglycemia in type 2 diabetes and delay of the thrombosis. The objective of the study was to investigate the toxicology effects of 5rolGLP-HV and guarantee its safety. In acute toxicity test, the mice were orally receiving 5rolGLP-HV at a single dose of 300 mg/kg or 2000 mg/kg. For sub-chronic toxicity study, the mice received 5rolGLP-HV at doses of 800 mg/kg or 1600 mg/kg for 9 weeks. No significant adverse effects were evident in acute and sub-chronic toxicity tests, indicating that the LD50 value is greater than 2000 mg/kg. Although the liver and kidney exhibited a little abnormal in sub-chronic toxicity study, they could recovery to normal after withdrawal 5rolGLP-HV for 2 weeks. In micronucleus assay, the mice received 5rolGLP-HV at doses of 250, 500, or 1000 mg/kg for two consecutive days. The micronucleus numbers and the polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) ratios among 5rolGLP-HV groups were within the normal range. Similarly, sperm aberration test demonstrated that 5rolGLP-HV had no teratogenic effect on the mice sperm. In conclusion, the combined results clearly demonstrated the safety of 5rolGLP-HV and support its use as a drug to treat diabetes and thrombosis.

HYPERGLYCEMIA; TYPE 2 diabetes; THROMBOSIS; LABORATORY mice; CHRONIC toxicity testing; NUCLEOLUS; ERYTHROCYTES

Applied Biochemistry & Biotechnology, 2016, Vol 180, Issue 7, p1276

0273-2289

Academic Journal

10.1007/s12010-016-2166-9