Hepatic sulfation

Although quercetin may stimulate UGT, it inhibits human hepatic sulfation of resveratrol, acetaminophen, dopamine, (-)-salbutamol, minoxidil, and paracetamol in vitro.69,98-101 This inhibition may be chemopreventive, as activation of some promutagens occurs via SULT reactions.68 However, SULT inhibition may also lead to the accumulation of some xenobiotics and possible toxicity. The magnitude of inhibition by quercetin of SULT appears dependent on the isoform because SULT1A3 is less affected than other isoforms, suggesting a tissue-dependent effect of quercetin.69... 

Hepatic sulfation. Sulfotransferases are both active on quercetin and strongly inhibited by it. 

Hepatic sulfation (or more correctly sulfonation) of drugs is a common phase II metabolic mechanism for increasing hydrophilicity in preparation for biliary or urinary excretion. Sulfonation may occur directly (i.e., acetaminophen) or may follow phase I oxidation (i.e., hydroxyphenobarbital). However, hepatic sulfonation can also... 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

Heparin Sulfate Proteoglycans Hepatic Lipase Hepatitis Hepatitis C Heptahelical Domain Heptahelical Receptors HERG-channels Heterologous Desensitization Heterologous Expression System Heterotrimeric G-Proteins Hidden Markov Model High-density Lipoprotein (HDL)... 

In a study of the metabolism of methyl parathion in intact and subcellular fractions of isolated rat hepatocytes, a high performance liquid chromatography (HPLC) method has been developed that separates and quantitates methyl parathion and six of its hepatic biotransformation products (Anderson et al. 1992). The six biotransformation products identified are methyl paraoxon, desmethyl parathion, desmethyl paraoxon, 4-nitrophenol, />nitrophenyl glucuronide, and /wiitrophenyl sulfate. This method is not an EPA or other standardized method, and thus it has not been included in Table 7-1. 

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Recently, molecular biology studies have been carried out on hepatic uptake transporters. With regard to the Na+-dependent hepatic uptake of bile acids, Na+-taurocholate cotransporting polypeptide (Ntcp/NTCP) has been cloned from both rodents and humans [14-17]. Ntcp/NTCP accepts bile salts, such as taurocholate and glycocholate, as well as some anionic compounds such as dehydroepian-drosterone sulfate and bromosulfophthalein [16, 18]. However, the presence of unidentified Na+-dependent transporters for anionic drugs (e.g., bumetanide) has also been suggested [19, 20]. 

Pesoia, G. R., Walle, T., Stereoselective sulfate conjugation of isoproterenol in humans comparison of hepatic, intestinal and platelet activity, Chirality 1993, 5, 602-609. 

Heparitin sulfate, 4 706 Hepatitis A vaccine, 25 492-493 Hepatitis B vaccine, 25 491 from yeast, 26 487 Hepatitis B virus (HBV), 3 135 antiviral therapy, 3 154-159 infection process, 3 153-154 Hepatitis B virus detection, method for, 14 153-154... 

Hepatotoxins include microcystins, which are cyclic heptapeptides (Fig. 5.1a) and cylindrospermopsin, a sulfated guanidinium alkaloid (Fig. 5. lb). Microcystins bind to certain protein phosphatases responsible for regulating the distribution of cytoskeletal proteins (Zurawell et al. 2005 Leflaive and Ten-Hage 2007). Hepatocytes exposed to microcystins eventually undergo cellular deformation, resulting in intra-hepatic bleeding and, ultimately, death (Carmichael 2001 Batista et al. 2003). In contrast, cylindrospermopsin appears to have a different mode of activity, possibly involving inhibition of protein or nucleotide synthesis (Codd et al. 1999 Froscio et al. 2003 Reisner et al. 2004). Nevertheless, microcystins are the most common cyanotoxins isolated from cyanobacterial blooms (Sivonen and Jones 1999). 

Pittz EP, Abraham R, Rourke D, et al. 1978. Effect of oral administration to mice of 30 ppm of mirex on the sodium dodecyl sulfate polyacrylamide gel electrophorectic patterns of hepatic microsomal proteins. Toxicol Appl Pharmacol 45(1) 335-336. 

Information regarding the distribution of the very commonly used detergent sodium lauryl sulfate (SLS) also appears in Table V. Twenty-four hrs. after injection of the form of SLS, most of it (65%) has been excreted in the urine of the shark. At the earlier time point, 4 hrs., the hepatic tissue has a higher concentration and quantity of the detergent than any other tissue. Muscle retained the isotope longer than did other tissues in this table and may represent sulfur exchange with endogenous substances. 

Comparative Toxicokinetics. The metabolism and excretion of orally administered phenol in 18 animal species have been compared to metabolism and excretion in humans (Capel et al. 1972). The rat was the most similar to the human with respect to the fraction of administered dose excreted in urine in 24 hours (95%) and the number and relative abundance of the 4 principal metabolites excreted in urine (sulfate and glucuronide conjugates of phenol and 1,4-dihydroxybenzene). The rat excreted a larger fraction of the orally administered dose than the guinea pig or the rabbit (Capel et al. 1972) and appears to be the least susceptible of the three species to respiratory, cardiovascular, hepatic, renal, and neurological effects of inhaled phenol (Deichmann et al. 1944). More rapid metabolism and excretion of absorbed phenol may account for the lower sensitivity of the rat to systemic effects of phenol. More information on the relative rates of metabolism of phenol in various species is needed to identify the most appropriate animal model for studying potential health effects in humans. 

Kim HJ, Cho JH, Klaassen CD. 1995. Depletion of hepatic 3 -phosphoadenosine 5 -phosphosulfate (PAPS) and sulfate in rats by xenobiotics that are sulfated. J Pharmacol Exp Ther 275 654-658. 

Abacavir sulfate has been associated with fatal hypersensitivity reactions. Do not restart abacavir following a hypersensitivity reaction to any abacavir containing product (see Warnino box) hepatic impairment previously demonstrated hypersensitivity to any of the components of the product. 

Hepatic Effects. A transient increase in serum bilirubin was observed in 3 of 10 workers who were hospitalized after drinking water during one work shift from a water fountain contaminated with nickel sulfate, nickel chloride, and boric acid (Sunderman et al. 1988). The workers who reported symptoms (20 of 35) or were hospitalized (10 of 35) were exposed to an estimated dose of 7.1-35.7 mg nickel/kg. The contribution of boric acid to these effects is not known. 

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