Role of calcium and arachidonic acid metabolites in creatine kinase release from isolated rat skeletal muscles damaged by organic cosolvents.
The objective of the present work is to provide additional experimental evidence which can help to differentiate between a direct solubilization mechanism versus an intracellular calcium mechanism of organic cosolvent-induced creatine kinase release from isolated rat skeletal muscles. An increase in cytosolic free calcium levels following exposure to propylene glycol was evaluated indirectly through the measurement of skeletal muscle glycogen levels. Skeletal muscle glycogen levels decreased significantly in propylene glycol-treated muscles compared to normal saline-treated controls; providing further evidence for the possible role of increased cytosolic calcium in organic cosolvent-induced muscle damage. The possible involvement of prostaglandins and leukotrienes which disrupt membrane integrity leading to propylene glycol-induced creatine kinase release was investigated via the use of cyclo-oxygenase and lipoxygenase inhibitors. Organic cosolvent-induced creatine kinase release was not significantly reduced when the muscles were incubated in the presence of cyclo-oxygenase inhibitors, lipoxygenase inhibitors, or a combination of a cyclo-oxygenase and lipoxygenase inhibitor. These findings suggest that in this experimental system prostaglandins and leukotrienes do not seem to be involved in organic cosolvent-induced alterations in sarcolemma integrity leading to the release of creatine kinase.
Brazeau
G A
GA
Department of Pharmaceutics, University of Houston College of Pharmacy, Texas.
Watts
S S
SS
Mathews
L S
LS
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D003402:Creatine Kinase / Q000096:biosynthesis*; D006003:Glycogen / Q000096:biosynthesis; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism*; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D016859:Lipoxygenase Inhibitors; D011409:Propylene Glycols; D011453:Prostaglandins; D016718:Arachidonic Acid; D019946:Propylene Glycol; D006003:Glycogen; D003402:Creatine Kinase; D001241:Aspirin; D002118:Calcium