In vivo alterations in lactate dehydrogenase (LDH) and LDH isoenzymes patterns by acute carbofuran intoxication

Abstract

Intoxication with an acute dose of carbofuran (1.5 mg/kg, sc) in male Sprague-Dawley rats evoked severe toxic manifestations characteristic of hypercholinergic preponderance with profound muscle fasciculations and convulsions during 30-60 min, lasting for about 2 h. Lactate dehydrogenase, a "biomarker" cytoplasmic enzyme catalyzing the reversible reaction of lactate-pyruvate, was represented by five electrophoretically distinct isoenzymes in the serum and tissues. The amounts of each isoenzyme in different tissues were widely varied and consequently the patterns were tissue specific. A 24-h time-course following carbofuran administration indicated a two-fold increase in the activity of total LDH in serum and more than 30% in hemidiaphragm and liver. The patterns of LDH isoenzymes in serum revealed a significant (P less than 0.01) increase in all the isoenzymes except LDH-4 (64% decrease). Analysis of each tissue revealed characteristic changes in LDH isoenzyme patterns indicating organ-specific tissue damage. These alterations in LDH and its isoenzymes, in addition to acetylcholinesterase inhibition, may be directly or indirectly related to the mechanism(s) of the toxic action, and also provide insight into the site/organ(s) of toxic injury, thus providing an early prognostic indicator.