Metabolite biliary

Another type of detoxication involves the production of cysteine conjugates, which are readily excreted. (Again, organomercury compounds show their affinity for -SH groups). Methyl mercuric cysteine is an important biliary metabolite in the rat and is degraded within the gut (presumably by microorganisms) to release inorganic mercury (see IAEA Report 137, 1972). 

Separation and purification of biliary metabolites isolation of methyl(17a-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione-21-yl-2, 3, 4 -O-triaeetyl-a-D-glucopyranosid)uronate... 

Levels of label in the liver, kidney, and plasma were determined for the donor and recipient rats when secretions from bile duct cannulated donor rats, given a dose of 100 mg/kg hexachlorobutadiene were infused directly into the bile duct of nonexposed recipient rats, and thereby into their intestines (Payan et al. 1991). In the donor rats, after 30 hours, the kidney contained 0.26% of the dose, the liver 0.11%, and the plasma 0.013% from the intestinally absorbed material. In the recipient rats, the kidney contained 0.15% of the dose, the liver 0.97%, and the plasma 0.009% from the resorbed biliary metabolites. For each tissue the level of label from resorbed metabolites was about two-thirds of that from the original dose. The kidneys contained more of the label than the liver in both instances, clearly identifying the kidneys as a target organ. 

Dekant et al. 1988b Nash et al. 1984 Reichert and Schutz 1986 Reichert et al. 1985). At the higher closes urinary excretion values of 5 to 10% were common (Nash et al. 1984 Reichert and Schutz 1986). Some of the hexachlorobutadiene label excreted in the urine originates from the biliary metabolites reabsorbed from the intestinal tract and processed by the kidneys for excretion. 

The contribution of reabsorbed biliary metabolites to urinary excretion is reflected in the differences in urinary excretion of label from bile duct cannulated rats and noncannulated rats. When a dose of 1 mg/kg hexachlorobutadiene in polyethylene glycol solution was given to bile duct cannulated male rats, the urine contained 11 % of the label after 72 hours in noncannulated rats given the same dose it contained 18% of the label (Payan et al. 1991). When a dose of 100 mg/kg was given, the urine of the cannulated rats contained 7% of the label and the urine of the noncannulated rats contained 9% after 72 hours. 

There are no specific treatments for reducing the body burden following absorption of hexachlorobutadiene. As discussed in Section 2.3, there is extensive reabsorption and enterohepatic recirculation of biliary metabolites, which are thought to play a major role in the nephrotoxicity of the... 

Payan JP, Beydon D, Fabry JP, et al. 1993. Partial contribution of biliary metabolites to nephrotoxicity, renal content and excretion of [ C]hexachloro-1,3-butadiene in rats. J AppI Toxicol 13 19-24. 

Kida, K. et al., Identification of biliary metabolites of (-)-epigallocatechin gallate in rats, J. Agric. Food Chem., 48, 4151, 2000. 

Yasuda T, Mizunuma S, Kano Y et al. Urinary and biliary metabolites of genistein in rats. Biol. 

Fish exposed to the reformulated Syndrill 80 20 (Mod) did not exhibit biliary metabolite fluorescence at the naphthalene wavelength relative to the negative control group (p = 0.302), whereas the fish exposed to the original Syndrill 80 20... 

Figure 11.2 Biliary metabolite levels in the bile offish exposed to SBMs, Syndrill 80 20, and Syndrill 80 20 (Mod) for 21 days. Indicates a significant difference (p < 0.05) from negative control fish, (a) Naphthalene...

Gagnon, M.M. and Holdway D.A. (2002) EROD activity serum SDH and biliary metabolites in sand flathead (Platycephalus bassensis) collected in Port Phillip Bay Australia. Mar. Pollut. ., 44, 230-237. 

The disposition of A-[ 4C]vinyl-2-pyrrolidone has been studied in male Sprague-Dawley rats following a single intravenous injection. The plasma half-life was 1.9 h. Up to 6 h after dosing, the highest tissue concentrations of radioactivity were found in the liver and small intestines. By that time, about 19% of the dose had been excreted in bile, yet, by 12 h, only about 0.4% had been excreted in faeces while about 75% had been excreted in urine. Thus, there appeared to be substantial enterohepatic recirculation of biliary metabolites. Very small quantities of the administered material were excreted unchanged. In a single rat, 12% of the urinary radioactivity was present as acetic acid. Other metabolites were not identified (McClanahan et al., 1984). 

N- Glucuronides have been isolated as urinary or biliary metabolites of many aromatic and aliphatic amines, the reaction being of minor quantitative importance in comparison to N- acetylation and other C- or A/-oxidative processes (see (B-80MI10909)). The only reported example of glucuronidation at a tertiary alicyclic nitrogen appears to be in... 

Heath, T. G. Mooney, J. P. Broersma, R. 1997. Narrow-bore liquid chromatography-tandem mass spectrometry with simultaneous radioactivity monitoring for partially characterizing the biliary metabolites of an arginine fluoroalkyl ketone analog of D-MePhe-Pro-Arg, a potent thrombin inhibitor. J. Chromatgr. B Biomed. Sci. Appl., 688,281-289. 

Intravenously administered biliary metabolites were rapidly eliminated in both bile and urine, supporting the proposition that the return of 1 from tissues was the rate determining step process after initial distribution. ... 

Schrenk D, Ingelman-Sundberg M, Bock KW. 1992. Influence of P-4502E1 induction on benzene metabolism in rat hepatocytes and on biliary metabolite excretion. Drug Metab Dispos 20(2) 137-141. 

Fujimaki, M. and Hakusui, H. (1990), Identification of Two Major Biliary Metabolites of Carvedilol in Rats, Xeiwbiotica, 20 1025-1034. 

Animal studies have indicated the major route of excretion to be urinary with at least 80% of the original dose generally eliminated within 24 h. Aldicarb is excreted primarily as aldicarb sulfoxide and sulfoxide oxime the parent compound is excreted only in trace amounts. Biliary metabolites have been shown to undergo resorption and urinary excretion. 

Figure 2. Thermospray A) LC/MS and B) LC/MS/MS spectra of SK F 96148 biliary metabolite Ml, the hydroxylated taurine conjugate.

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