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

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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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Acknowledgments

This study is supported by the Key Technologies R&D Program of Tianjin (14ZCZDSY00013).

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  1. Minggang Li

    Present address: College of Life Science, Nankai University, 94 Weijin Road, Nankai District, Tianjin, 300071, China

Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China

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

  2. Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China

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

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  1. Zaizhong Ni
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Correspondence to Minggang Li.

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The experiments were approved and supervised by the Institutional Animal Care and Use Committee of Nankai University.

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Ni, Z., Wang, B., Ma, X. et al. Toxicology Assessment of a Dual-Function Peptide 5rolGLP-HV in Mice. Appl Biochem Biotechnol 180, 1276–1285 (2016). https://doi.org/10.1007/s12010-016-2166-9

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  • DOI: https://doi.org/10.1007/s12010-016-2166-9

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