Effects of the ionophore antibiotic monensin on hepatic biotransformationsand target organ morphology in rats

As a preliminary in vivo approach in order to study the mechanism of toxici ty of the veterinary anticoccidial monensin, male Wistar rats were orally a dministered 0, 2 and 12 mg kg(-1) body wt. day(-1) of monensin for 7 days. At the end of the experiment, effects of the ionophore on serum creatine ki nase, lactic dehydrogenase and selected drug metabolising enzyme activities were investigated. Furthermore, liver, heart and quadriceps femoris muscle samples were submitted to morphological investigations. Clinical signs or increasing levels of enzymic markers of muscle injury attributable to monen sin toxicosis have never been observed in treated animals. As a matter of f act all drug metabolising enzymes activities checked have not shown signifi cant changes, except for a significant decrease of ethoxyresorufin O-deethy lase (up to 31%) and aminopyrine N-demethylase (17%) activities. Morphologi cally, mitochondrial cristae fragmentation and initial formation of myelini c sheaths-like structures have been noticed in heart and muscle fibres. As far as rat study is concerned, these results confirm heart and muscle as ta rget organs of monensin toxicity. In addition, these findings suggest that the inhibition of hepatic biotransformation processes following the i.p. ad ministration of the ionophore, as reported previously by other authors, mig ht reflect unspecific cellular toxic effects rather than a specific enzyme damage. (C) 1999 The Italian Pharmacological Society.