Attenuation of stretch-induced histopathologic changes of skeletal muscles by quinacrine.
Quinacrine is an inhibitor of phospholipase A(2), an enzyme thought to be involved in activity-related injury of skeletal muscles. Histopathologic changes after injury by stretches of activated plantar-flexor muscles were measured in untreated and quinacrine-treated rats. On day 4 of treatment (50 mg.kg(-1) intraperitoneally for 5 days), 30 stretches were induced by ankle rotation after muscles reached a maximal isometric force. During the stretch protocol, peak stretch forces and isometric force deficits after each stretch [total deficits 56.7 +/- 2.8% (untreated rats) and 59.6 +/- 1.7% (quinacrine-treated rats)] were similar for both groups (n = 6 each). Two days after the stretch protocol, histopathologic changes were evaluated using antibody staining on cross-sections of gastrocnemius medialis muscles. Swollen myofibers devoid of desmin were identified. Similar cells, but not all swollen myofibers, in adjacent sections stained for albumin. Quinacrine reduced the number of desmin-negative and albumin-positive cells by 88% (P < 0.05) and 84% (P < 0.05), indicating that it attenuated histopathologic changes that follow stretch injury of activated skeletal muscles. Histopathologic changes following muscle injury or myopathic disease may thus be reduced or even prevented by selective drug intervention, thereby reducing the risk of muscle fibrosis. Muscle Nerve 27: 65-71, 2003
Willems
Mark E T
ME
Department of Physiology and Pharmacology, West Virginia University, P.O. Box 9229, Morgantown, West Virginia 26506-9229, USA.
Stauber
William T
WT
D000418:Albumins / Q000032:analysis; D000818:Animals; D003893:Desmin / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005355:Fibrosis; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000473:pathology; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology*; D009135:Muscular Diseases / Q000188:drug therapy* / Q000473:pathology; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D003893:Desmin; D004791:Enzyme Inhibitors; D011796:Quinacrine