Boles J W, Klaassen C D
Center for Environmental and Occupational Health, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Toxicol Lett. 1999 May 20;106(1):1-8. doi: 10.1016/s0378-4274(99)00017-x.
Sulfation is the conjugation of chemicals with sulfate, which usually decreases, but occasionally increases, their biological effects. The phenol-sulfotransferase inhibitor pentachlorophenol (PCP) is often used to distinguish the biological effects of a chemical from its sulfate conjugate. Recently, molybdate has been shown to decrease the hepatic concentration of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for sulfation. Therefore, the present study was designed to compare the effectiveness and specificity of molybdate and PCP as inhibitors of sulfation. Alpha-naphthol (125 and 250 micromol/kg, i.p.) was administered to rats and the sulfate and glucuronide conjugates excreted into urine were quantified for this comparison. Molybdate (5.0, 7.5, and 10 mmol/kg) decreased the 24-h cumulative urinary excretion of the sulfate conjugate of the lower dose of alpha-naphthol by 54, 53, and 55%, respectively, with corresponding compensatory increases in glucuronide excretion at the two lower doses of molybdate. PCP (20, 40, and 80 micromol/kg) similarly decreased the sulfation of alpha-naphthol by 48, 38, and 41%, respectively, but prevented compensatory increases in glucuronide excretion. Molybdate (2.5, 5.0, and 7.5 mmol/kg) decreased the sulfation of the higher dose of alpha-naphthol by 21, 30, and 44%, respectively, again with corresponding compensatory increases in glucuronide excretion. In contrast, PCP did not decrease significantly the sulfation of the higher dose of alpha-naphthol. These data suggest that molybdate is equally or more effective than PCP at inhibiting sulfation of alpha-naphthol, and appears to be more specific.
硫酸化作用是指化学物质与硫酸盐结合，这通常会降低其生物学效应，但偶尔也会增加。酚 - 磺基转移酶抑制剂五氯苯酚（PCP）常被用于区分一种化学物质与其硫酸盐结合物的生物学效应。最近，已表明钼酸盐可降低硫酸化作用的共底物3'-磷酸腺苷5'-磷酸硫酸酯（PAPS）的肝脏浓度。因此，本研究旨在比较钼酸盐和PCP作为硫酸化作用抑制剂的有效性和特异性。将α-萘酚（125和250微摩尔/千克，腹腔注射）给予大鼠，并对排泄到尿液中的硫酸盐和葡萄糖醛酸结合物进行定量以进行此比较。钼酸盐（5.0、7.5和10毫摩尔/千克）分别使较低剂量α-萘酚的硫酸盐结合物的24小时累积尿排泄量降低了54%、53%和55%，在较低剂量的钼酸盐作用下，葡萄糖醛酸排泄量相应地出现代偿性增加。PCP（20、40和80微摩尔/千克）同样分别使α-萘酚的硫酸化作用降低了48%、38%和41%，但阻止了葡萄糖醛酸排泄量的代偿性增加。钼酸盐（2.5、5.0和7.5毫摩尔/千克）分别使较高剂量α-萘酚的硫酸化作用降低了21%、30%和44%，同样伴随着葡萄糖醛酸排泄量的相应代偿性增加。相比之下，PCP并未显著降低较高剂量α-萘酚的硫酸化作用。这些数据表明，在抑制α-萘酚的硫酸化作用方面，钼酸盐与PCP同样有效或更有效，并且似乎更具特异性。
