title: Notexin causes greater myotoxic damage and slower functional repair in mouse skeletal muscles than bupivacaine.
abstract: Although the myotoxins bupivacaine and notexin are employed for studying processes that regulate muscle regeneration after injury, no studies have compared their efficacy in causing muscle damage or assessing functional regeneration in mouse skeletal muscles. Bupivacaine causes extensive injury in rat muscles but its effects on mouse muscles are variable. We compared functional and morphological properties of regenerating mouse extensor digitorum longus (EDL) muscles after notexin or bupivacaine injection and tested the hypothesis that muscle damage would be more extensive and functional repair less complete after notexin injection. Bupivacaine caused degeneration of 45% of fibers and reduced maximum force (Po) to 42% of control after 3 days. In contrast, notexin caused complete fiber breakdown and loss of functional capacity after 3 days (P < 0.05). At 7 and 10 days after bupivacaine, Po was restored to 65% and 71% of control, respectively, whereas Po of notexin-injected muscles was only 10% and 39% of control at these time-points, respectively (P < 0.05). At 7 and 10 days after bupivacaine, approximately 30% of fibers were centrally nucleated (regenerating), whereas notexin-injected muscles were comprised entirely of regenerating fibers (P < 0.05). The results demonstrate that notexin causes a more extensive and complete injury than bupivacaine, and is a useful model for studying muscle regeneration in mice.
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Plant
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Colarossi
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
mesh_terms: D000779:Anesthetics, Local / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000633:toxicity*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D003603:Cytotoxins; D004546:Elapid Venoms; D009498:Neurotoxins; C005082:notexin; D002045:Bupivacaine