Effects of the ionophore antibiotic monensin on hepatic biotransformations and target organ morphology in rats.
As a preliminary in vivo approach in order to study the mechanism of toxicity of the veterinary anticoccidial monensin, male Wistar rats were orally administered 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 kinase, 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 monensin toxicosis have never been observed in treated animals. As a matter of fact all drug metabolising enzymes activities checked have not shown significant changes, except for a significant decrease of ethoxyresorufin O-deethylase (up to 31%) and aminopyrine N-demethylase (17%) activities. Morphologically, mitochondrial cristae fragmentation and initial formation of 'myelinic 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 target organs of monensin toxicity. In addition, these findings suggest that the inhibition of hepatic biotransformation processes following the i.p. administration of the ionophore, as reported previously by other authors, might reflect unspecific cellular toxic effects rather than a specific enzyme damage.
Dipartimento di Patologia Animale, Settore di Farmacologia e Tossicologia, Università degli Studi di Torino, via Nizza 52, Torino, 10126, Italy.
M
M
Dacasto
L
L
Ceppa
E
E
Cornaglia
F
F
Valenza
M
M
Carletti
A
A
Bosio
S
S
Bosia
G
G
Ugazio
C
C
Nebbia
D000818:Animals; D000981:Antiprotozoal Agents / Q000633:toxicity*; D001711:Biotransformation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D008985:Monensin / Q000633:toxicity*; D018482:Muscle, Skeletal / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000981:Antiprotozoal Agents; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D008985:Monensin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D005978:Glutathione