Skeletal muscle atrophy induced by intramuscular repeated dose of botulinum toxin type A in rats.
Botulinum toxin type A was intramuscularly administered to Sprague-Dawley rats once a day for 28 days at doses of 1, 3, and 9 ng kg-1 day-1 to investigate the possibility of unanticipated toxicity of repeated dose. A dose-related decrease in body weight gain was noted and lasted throughout the 4-week recovery period. Paralytic gait was a common clinical sign observed in the animals dosed at >or=3 ng kg-1 day-1 and muscle atrophy at 9 ng kg-1 day-1. Decreased creatinine was monitored in both males and females treated at 9 ng kg-1 day-1. Microscopic examination of the quadriceps femoris muscle, the test article application site, confirmed the muscle atrophy with a decrease in myofiber diameter and an increase of myofiber nuclei and intermyofiber connective tissue. Although antibody against botulinum toxin type A was detected in the sera from both males and females at 9 ng kg-1 day-1, no immunogenicity-related changes or lesions were noted. In conclusion, no other side effects of the botulinum toxin type A injection except the decrease in body weight gain and the muscle atrophy at the administration site were noted in the 28-day intramuscular repeated dose study.
Choi
Woo H
WH
Korea Institute of Toxicology, Yusung-gu, Daejeon, Korea.
Song
Chang W
CW
Kim
Yong B
YB
Ha
Chang S
CS
Yang
Gi-H
GH
Woo
Hee-D
HD
Jung
Hyun H
HH
Koh
Woo S
WS
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005260:Female; D005684:Gait / Q000187:drug effects; D007273:Injections, Intramuscular; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D009133:Muscular Atrophy / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000907:Antibodies, Bacterial; D009465:Neuromuscular Agents; D003404:Creatinine; D019274:Botulinum Toxins, Type A