Naphthalene cataract has been widely used as a model for human senile cataract because oxidation is the basic mechanism of this cataract formation. Recent interest in this cataract has been renewed by the evidence that some of the aldose reductase (AR) inhibitors prevent the formation of cataract in naphthalene-fed rats. Although AR is a member of a family of aldo-keto reductases, which utilizes NADPH to reduce a wide range of aromatic and aliphatic aldehydes and ketones to their corresponding alcohols, this enzyme also possesses the dehydrogenase activity and utilizes naphthalene-1,2-dihydrodiol, one of the major metabolites of naphthalene. Because dihydrodiol dehydrogenase is not present in rat lens, the activity to naphthalene-1,2-dihydrodiol is mainly derived from AR. The analysis by both LCMS and GCMS confirms that the metabolite from naphthalene-1,2-dihydrodiol by rat lens AR is 1,2-naphthoquinone. Rat lens incubated with naphthalene-1,2-dihydrodiol generates the dark yellowish protein-naphthoquinone adducts that are also created by the incubation of lens protein and naphthalene-1,2-dihydrodiol in vitro. Both hydantoin-containing and nonhydantoin AR inhibitors prevent this protein modification. The evidence clearly indicates that AR is important in the metabolism of naphthalene in rat lens and eventually plays a key role in the formation of cataract. Because human AR has the same dihydrodiol dehydrogenase activity, AR may play a role in some toxic cataracts.
