Abstract
trans-4-Acetylaminostilbene (trans-AAS) is acutely toxic to rats. Animals can be protected from the effects of a lethal dose by pretreatment with methylcholanthrene (MC), but not with phenobarbital (PB). In order to study the effects of these pretreatments on pharmacokinetic parameters, single, acute toxic doses of 3H-trans-AAS were orally administered to female Wistar rats and metabolism and excretion studied in untreated and PB- and MC-pretreated animals. MC pretreatment enhanced the rate of metabolism and the excretion of metabolites into the bile, but did not alter urinary excretion. After 3 days, 46, 86, and 52% of the administered dose was excreted, respectively, in untreated, MC-pretreated, and PB-pretreated animals. MC pretreatment modified both phase I and phase II metabolism of trans-AAS. Urinary excretion of unconjugated metabolites was decreased accompanied by an increased formation of sulfates. Biliary excretion of glucuronides and conjugated polar metabolites was increased by MC pretreatment. It is concluded that MC protects rats from acute trans-AAS toxicity by increasing the rate of total metabolism and enhancing metabolic (conjugation) pathways of inactivation relative to putative activation by oxidative metabolism.
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|