Dynamic muscle paralytic effects of a novel botulinum toxin A free of neurotoxin-associated proteins

被引:1
|
作者
Liu, Wu-chao [1 ]
Su, Jun-hui [2 ,3 ]
Feng, Ya [2 ]
Xiang, Xue-rui [2 ,3 ]
Pan, Li-zhen [2 ]
Liu, Ying [2 ]
Ma, Lin [2 ]
Nie, Zhi-yu [2 ]
Zhang, Xue-ping [4 ]
Jin, Ling-jing [1 ,3 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Sunshine Rehabil Ctr, Shanghai YangZhi Rehabil Hosp, Shanghai 201613, Peoples R China
[2] Tongji Univ, Shanghai Tongji Hosp, Sch Med, Dept Neurol, Shanghai, Peoples R China
[3] Tongji Univ, Sch Med, Neurotoxin Res Ctr,Minist Educ Peoples Republ Chi, Key Lab Spine & Spinal Cord Injury Repair & Regen, Shanghai, Peoples R China
[4] Lanzhou Inst Biol Prod Co Ltd, Ctr Gansu Prov Vaccine Engn Res, Dept Toxin Preparat, Lanzhou 730046, Gansu, Peoples R China
来源
PHARMACOLOGY RESEARCH & PERSPECTIVES | 2022年 / 10卷 / 03期
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
botulinum toxin A; chinbotulinumtoxin A; complex proteins; muscle strength; COMPLEXING PROTEINS; INCOBOTULINUMTOXINA; POTENCY; ONABOTULINUMTOXINA; XEOMIN(R); ADHESION;
D O I
10.1002/prp2.955
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Structurally, botulinum toxin type A (BTX-A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX-As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time-to-peak paralytic effect of other BTX-As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX-As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin-eosin staining was performed. In conclusion, compared with other BTX-As, A/Chin showed rapid and steady time-to-peak paralytic effect and long-term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.
引用
收藏
页数:7
相关论文
共 50 条
  • [1] AN EXPERIMENTAL STUDY ABOUT NEUROTOXIC POTENCY OF A NOVEL BOTULINUM TOXIN TYPE A FREE OF NEUROTOXIN-ASSOCIATED PROTEINS BASED ON MUSCLE STRENGTH MEASUREMENT
    Liu Wuchao
    Feng Ya
    Su Junhui
    Zhang Zheng
    Pan Lizhen
    Zou Libin
    Zhang Xueping
    Jin Lingjing
    TOXICON, 2018, 156 : S117 - S117
  • [2] INSIGHTS INTO THE PRODUCTION OF NEUROTOXIN-ASSOCIATED PROTEINS FROM CLOSTRIDIUM BOTULINUM STRAIN BELUGA
    Przykopanski, Adina
    Kruger, Maren
    Luebke, Johanna
    Kroh, Amelie
    Jin, Rongsheng
    Dorner, Brigitte G.
    Rummel, Andreas
    TOXICON, 2018, 156 : S94 - S94
  • [3] Comparative role of neurotoxin-associated proteins in the structural stability and endopeptidase activity of botulinum neurotoxin complex types A and E
    Kukreja, Roshan V.
    Singh, Bal Ram
    BIOCHEMISTRY, 2007, 46 (49) : 14316 - 14324
  • [4] CHIMERAS OF ANTHRAX TOXIN AND BOTULINUM NEUROTOXIN AS NOVEL ANALGESIC PROTEINS
    Yang, Nicole
    Liu, Sai Man
    Marlin, Sandra
    Lewandowska, Agnieszka
    Heyang, Michelle
    Voisin, Tiphaine
    Tripathi, Vineeta
    Kalinichev, Mikhail
    Chaddock, John
    Collier, R. John
    Foster, Keith
    Chiu, Isaac
    TOXICON, 2018, 156 : S118 - S118
  • [5] The structure of the neurotoxin-associated protein HA33/A from Clostridium botulinum suggests a reoccurring β-trefoil fold in the progenitor toxin complex
    Arndt, JW
    Gu, J
    Jaroszewski, L
    Schwarzenbacher, R
    Hanson, MA
    Lebeda, FJ
    Stevens, RC
    JOURNAL OF MOLECULAR BIOLOGY, 2005, 346 (04) : 1083 - 1093
  • [6] Botulinum neurotoxin serotype C: A novel effective botulinum toxin therapy in human
    Eleopra, R
    Tugnoli, V
    Rossetto, O
    Montecucco, C
    DeGrandis, D
    NEUROSCIENCE LETTERS, 1997, 224 (02) : 91 - 94
  • [7] Capsaicin Protects Mouse Neuromuscular Junctions From The Paralytic Effects Of Botulinum Neurotoxin A
    Thyagarajan, Baskaran
    Krivitskaya, Natalia
    Hognason, Kormakur
    Potian, Joseph G.
    McArdle, Joseph J.
    BIOPHYSICAL JOURNAL, 2009, 96 (03) : 268A - 268A
  • [8] The new function of neurotoxin associated proteins in Clostridium botulinum neurotoxin complex.
    Cai, S
    Sarkar, HK
    Singh, BR
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1998, 216 : U559 - U559
  • [9] Stability of Xeomin®, a preparation of botulinum neurotoxin type A, free of complexing proteins
    Grein, S.
    Mander, G. J.
    Grafe, S.
    MOVEMENT DISORDERS, 2007, 22 : S18 - S18
  • [10] Botulinum Neurotoxin Type A Free of Complexing Proteins (XEOMIN®) in Focal Dystonia
    Wolfgang H. Jost
    Jörg Blümel
    Susanne Grafe
    Drugs, 2007, 67 : 669 - 683