Biochemical aspects of bupivacaine-induced acute muscle degradation.
A single injection of a local anaesthetic, bupivacaine, into the soleus muscle of adult rat has a severe mytoxic effect, i.e. rapid dissolution of myofilaments and degradation of myofibrillar proteins shortly after injection. Increased lysosomal enzymes were observed in homogenates of affected muscle. The activity of potent proteolytic enzyme, cathepsins B and L (assayed against a new synthetic substrate succinyl-Tyr-Met-naphthylamide), gradually increased and reached a plateau value that was 11-fold greater than the control 48 h after bupivacaine injection. The chronological change in the activity of cathepsins B and L was reflected in the myofibrillar protein pattern in bupivacaine-treated muscle. To determine whether the increase in lysosomal peptide hydrolases is due to activation of muscle lysosomes or not, mononuclear cells were separated from both injected and control muscles. The activity of cathepsins B and L in the lysate from injured muscle was 180-fold higher than the control. Affinity-purified antibody was used to study the intracellular localization of cathepsin B by immunohistochemical procedures. The results were consistent with the biochemical observation that the main source of cathepsin B in muscle homogenates was infiltrated mononuclear cells. Therefore, we conclude that the increased lysosomal enzymes may be derived mainly from mononuclear cells (macrophages), not from muscle lysosomes, in bupivacaine-induced acute muscle degeneration.
D000818:Animals; D002045:Bupivacaine / Q000009:adverse effects*; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D005455:Fluorescent Antibody Technique; D008264:Macrophages / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D002045:Bupivacaine