Toxicology Assessment of a Dual-Function Peptide 5rolGLP-HV in Mice |
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Authors: | Zaizhong Ni Bin Wang Xiaofeng Ma Huikun Duan Pingzhe Jiang Xiaodan Li Qian Wei Xiangzhen Ji Minggang Li |
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Affiliation: | 1.State Key Laboratory of Medicinal Chemical Biology,Nankai University,Tianjin,China;2.Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science,Nankai University,Tianjin,China;3.College of Life Science,Nankai University,Tianjin,China |
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Abstract: | 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. |
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