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.
Toxicology. 1998 May 15;127(1-3):121-7. doi: 10.1016/s0300-483x(98)00029-8.
Sulfation requires the activity of sulfotransferases to transfer the sulfuryl group to the substrate from the activated form of sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Inhibition of the sulfate reaction is an important aspect in evaluating the role of sulfation in toxicology. Molybdate decreases hepatic PAPS and its precursor, inorganic sulfate, and could be used as a tool to inhibit the sulfation reaction. The present study was designed to determine the effect of molybdate on the sulfation of two compounds (harmol and alpha-naphthol), for which sulfation is the predominate pathway of biotransformation. Molybdate (7.5 mmol/kg; p.o.) given 4 h prior to the start of harmol infusion (2.5 micromol/kg/min) decreased serum harmol-sulfate concentrations by 32 and 45%, at 45 and 60 min, respectively. This was paralleled by decreases in the cumulative biliary excretion of harmol-sulfate of 37 and 43%, at 45 and 60 min, respectively. Molybdate (5.0 mmol/kg, p.o.) decreased the 24-h cumulative urinary excretion of naphthyl-sulfate by 55% for a 125-micromol/kg i.p. dose of alpha-naphthol, with the greatest decrease (63%) occurring during the first 4 h. These results suggest that molybdate can inhibit the sulfation of compounds that are highly sulfated. Thus, molybdate may prove useful in future studies to examine the pharmacological and toxicological significance of sulfation of xenobiotics.
硫酸化作用需要硫酸转移酶的活性，以便将硫酸酰基从硫酸的活化形式3'-磷酸腺苷5'-磷酸硫酸酯（PAPS）转移至底物。抑制硫酸反应是评估硫酸化作用在毒理学中作用的一个重要方面。钼酸盐会降低肝脏中的PAPS及其前体无机硫酸盐的含量，可作为抑制硫酸化反应的一种工具。本研究旨在确定钼酸盐对两种化合物（哈尔满和α-萘酚）硫酸化作用的影响，硫酸化是这两种化合物生物转化的主要途径。在开始输注哈尔满（2.5微摩尔/千克/分钟）前4小时口服给予钼酸盐（7.5毫摩尔/千克），在45分钟和60分钟时，血清硫酸哈尔满浓度分别降低了32%和45%。与之相对应的是，硫酸哈尔满的累积胆汁排泄量在45分钟和60分钟时分别降低了37%和43%。对于腹腔注射剂量为125微摩尔/千克的α-萘酚，口服钼酸盐（5.0毫摩尔/千克）使硫酸萘酯的24小时累积尿排泄量降低了55%，其中在最初4小时内下降幅度最大（63%）。这些结果表明，钼酸盐能够抑制高度硫酸化化合物的硫酸化作用。因此，钼酸盐在未来研究中可能有助于检验外源性物质硫酸化的药理学和毒理学意义。
