Toluene-induced hearing loss in phenobarbital treated rats.
Exposure to aromatic organic solvents may induce hearing loss in rats, the cochlea being the primary target. The aim of this study which was carried out in rat, was to evaluate the impact of the hepatic metabolism of toluene on its ototoxic potency. To this end, the solvent hepatic metabolism was shifted by treating the rats with 50 mg/kg/d of phenobarbital (PhB), a potent inducer of the microsomal cytochromes P450 system, alcohol and aldehyde dehydrogenases, and glutathione-S-transferases. The two main urinary metabolites of the oxidative and conjugate pathways [hippuric (HA) and benzyl mercapturic acids (BMA) respectively] confirmed the efficacy of the PhB treatment. For the PhB-induced rats, the amount of excreted HA increased by 43% and the amount of BMA by 35%. Auditory function impairments were assessed using auditory-evoked potentials. On completion of the auditory tests, the organs of Corti were dissected to evaluate hair cell losses. The permanent auditory threshold shifts were approximately 15 dB greater in the toluene-exposed rats than in the PhB-induced rats. Both the functional and morphological data confirmed that PhB treatment can decrease the ototoxic potency of toluene.
Campo
Pierre
P
Institut National de Recherche et de Sécurité, Département Polluants et Santé, Avenue de Bourgogne, BP 27, Vandoeuvre, 54501 cédex, France. Pierre.campo@inrs.fr
Waniusiow
Delphine
D
Cossec
Benoît
B
Lataye
Robert
R
Rieger
Benoît
B
Cosnier
Frédéric
F
Burgart
Manuella
M
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000704:Analysis of Variance; D000818:Animals; D001299:Audiometry / Q000379:methods; D001309:Auditory Threshold / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D034381:Hearing Loss / Q000139:chemically induced* / Q000188:drug therapy / Q000652:urine; D006626:Hippurates / Q000378:metabolism; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000502:physiology; D010634:Phenobarbital / Q000627:therapeutic use*; D000091402:Prohibitins; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D014050:Toluene / Q000633:toxicity* / Q000652:urine
D018691:Excitatory Amino Acid Antagonists; D006626:Hippurates; C000717332:Phb protein, rat; D000091402:Prohibitins; D014050:Toluene; C030514:hippuric acid; D000111:Acetylcysteine; C029319:S-benzyl-N-acetyl-L-cysteine; D010634:Phenobarbital