Carbofuran-induced alterations (in vivo) in high-energy phosphates, creatine kinase (CK) and CK isoenzymes.
Male Sprague-Dawley rats administered with an acute sublethal dose of carbofuran (1.5 mg/kg, s.c.) developed the signs of peak hypercholinergic activity during 30-60 min. At this time, in hemidiaphragm muscle, a significant decrease in ATP (28%) and phosphocreatine (PC) (29%) occurred without concurrent change in AMP and creatine (CR). A significant decrease in the levels of total adenine nucleotides (ATP + ADP + AMP) (20%) and total creatine compounds (PC + CR) (17%) was evident. The decline in the corresponding ratios of ATP/ADP (26%), ATP/AMP (39%), and PC/CR (20%) was therefore suggestive of greater utilization of ATP and PC in response to their increased demand for high-frequency muscle fasciculations. The energy charge = ATP + 1/2 ADP/(ATP + ADP + AMP), an index of high-energy phosphate adequacy in hemidiaphragm, remained unchanged. A significant (p less than 0.01) increase in serum magnesium with no concurrent change in calcium was also evident. The observed higher activity (152%) of total CK (EC 2.7.3.2) in the serum induced by carbofuran was possibly a reflection of more than a twofold increase in CK-BB isoenzyme (CK-1) and 141% increase in CK-MM isoenzyme (CK-3), which also strengthens our findings of enhanced synthesis of ATP and PC. Increased levels of CK-MM isoenzyme in the brain (253%) and hemidiaphragm (195%); and depletion of CK-BB isoenzyme in the hemidiaphragm (0%), heart (42%), and brain (77%), and of CK-MB isoenzyme (CK-2) in the brain (4%) and hemidiaphragm (14%), appeared to be the major contributory factors leading to enhanced serum CK activity.
Gupta
R C
RC
Toxicology Section, Murray State University, Breathitt Veterinary Center, Hopkinsville, Kentucky 42241-2000.
Goad
J T
JT
Kadel
W L
WL
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002118:Calcium / Q000097:blood; D002235:Carbofuran / Q000506:poisoning / Q000633:toxicity*; D003401:Creatine / Q000378:metabolism*; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects*; D003964:Diaphragm / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007527:Isoenzymes; D008274:Magnesium / Q000097:blood; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D001786:Blood Glucose; D007527:Isoenzymes; D010725:Phosphocreatine; D003402:Creatine Kinase; D008274:Magnesium; D003401:Creatine; D002235:Carbofuran; D002118:Calcium