Phenobarbital-type P-450 inducers protect rats against metaldehyde toxicity.
The mechanism of metaldehyde toxicity is unclear. It may be due to the compound itself or, at least in part, to acetaldehyde resulting from the hydrolysis of metaldehyde in the stomach. In this study, we orally dosed rats with twice the LD50 of metaldehyde following no pretreatment (control) or pretreatment with 1 of 3 different cytochrome P-450 inducers either phenobarbital or o,p'-DDD (inducers of cytochromes P-450 IIB and IIIA) or 3-methylcholanthrene (an inducer of P-450 IA). Our results show strong protection against metaldehyde poisoning afforded by the phenobarbital-DDD P-450 inducers, but only weak protection with 3-methylcholanthrene pretreatment. Acetaldehyde administered at the same molarity failed to produce the clinical signs of metaldehyde toxicity and no clinical differences were observed between any of the pretreated groups.
Tardieu
D
D
Department des Sciences Biologiques et Fonctionnelles, Ecole Nationale Veterinaire, Toulouse, France.
Thouvenot
N
N
Fargier
C
C
de Saqui-Sannes
P
P
Petit
C
C
D000079:Acetaldehyde / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003632:Dichlorodiphenyldichloroethane / Q000008:administration & dosage / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D006868:Hydrolysis; D006993:Hypnotics and Sedatives; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000633:toxicity; D008975:Molluscacides / Q000008:administration & dosage / Q000633:toxicity*; D010634:Phenobarbital / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D006993:Hypnotics and Sedatives; D007306:Insecticides; D008975:Molluscacides; C002935:metaldehyde; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D000079:Acetaldehyde; D003632:Dichlorodiphenyldichloroethane; D010634:Phenobarbital