title: Toxicology Assessment of a Dual-Function Peptide 5rolGLP-HV in Mice.
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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Zaizhong
authors.initials: Z
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Huikun
authors.initials: H
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Pingzhe
authors.initials: P
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Xiangzhen
authors.initials: X
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China. mgl@nankai.edu.cn.|Key Laboratory for Bioactive Materials of the Ministry of Education, Institute of Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, China. mgl@nankai.edu.cn.|College of Life Science, Nankai University, 94 Weijin Road, Nankai District, Tianjin, 300071, China. mgl@nankai.edu.cn.
authors.forename: Minggang
authors.initials: M
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000633:toxicity*; D006629:Hirudins / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D010455:Peptides / Q000008:administration & dosage / Q000633:toxicity*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000633:toxicity*; D013094:Spermatozoa / Q000187:drug effects; D018675:Toxicity Tests; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: C000613574:5rolGLP-HV fusion peptide; D006629:Hirudins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D052216:Glucagon-Like Peptide 1
keywords: 5rolGLP-HV; Acute toxicity; Micronucleus; Sperm aberration; Sub-chronic toxicity; Toxicology