Does liver control susceptibility to toluene ototoxicity?
Abstracts of the Twenty-Third Annual Mid-Winter Research Meeting of the Association for Research in Otolaryngology. Popelka GR, ed. St. Petersburg Beach, FL: Association for Research in Otolaryngology, 2000 Feb; :118
A number of epidemiological studies have implicated toluene as ototoxic in humans (Morata et al, 1995). Toluene cochlear ototoxicity has been conclusively demonstrated in the rat and mouse (Johnson & Canlon, 1994). Previously we showed no permanent ototoxicity in the chinchilla to very high levels of toluene inhalation exposure (>2000 ppm)(Davis et al, ARO, 1996). Also, others have not been able to produce toluene ototoxicity in the guinea pig. It has been hypothesized that rat and mouse liver handle toluene differently than chinchilla and guinea pig with the implication that human livers are more rat-like than chinchilla-like. Normal rat, chinchilla and human liver samples were assayed for their ability to convert toluene to water-soluble metabolites. Cytochrome P450 enzymes CYP2E1, CYP2C, CYP2Bx and CYP1A1/2 are most responsible for the oxidative biotransformation of toluene. Liver microsomes were prepared by differential centrifugation. Microsomal content was determined by ELISA in samples from all species. Microsomes were also incubated with toluene to examine the relative formation of the toluene metabolite, benzyl alcohol. Microsomes were found to contain similar levels of CYP1A1/2. CYP2B and CYP2E1 were markedly higher in chinchilla microsomes than rats or humans. Metabolism of toluene to benzyl alcohol was ranked as chinchilla > rat > human. These data indicate differences between the species in liver enzyme activities responsible for toluene biotransformation. While it is not clear whether toluene ototoxicity could be prevented by differences in metabolic capacity, the data present evidence for greater elimination of toluene by the chinchilla compared to either rat or man.
Ototoxicity; Hearing-disorders; Hearing-impairment; Hearing-loss; Solvents; Metabolism; Liver-function; Liver-microsomal-metabolism; Liver-microsomal-enzymes; Liver-microsomes
Abstracts of the Twenty-Third Annual Mid-Winter Research Meeting of the Association for Research in Otolaryngology.