Metabolite in the rat

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). 

It is known that nitrosamines with side-chains longer than methyl are metabolically hydroxylated on virtually every carbon. For example, the urinary metabolites in the rat of di-n-butylnitrosamine include the glucuronides of the following hydroxylated nitrosamines (42). 

Aniline is rapidly and extensively metabolized following oral administration. In the pig and sheep, approximately 30% of a 50-mg/kg dose of 14C-labeled aniline was excreted in the urine, as measured by 14C activity, within 3 h after administration, whereas approximately 50% of the dose was excreted in rats. Within 24 h, more than half the administered dose was excreted by pigs and sheep and 96% of the dose was excreted by rats. Fecal radioactivity was low. A-acetylated metabolites accounted for most of the excretion—/V-acetyl-/>-aminophenyl glucuronide being the primary metabolite in sheep and pig urine and /V-acetyl-/>-aminophenyl sulfate being the primary metabolite in the rat (Kao et al. 1978). Biologic monitoring of workers exposed to aniline showed that /i-aminophenol constituted 15-55% of the parent compound in the urine the o- and ra-isomers were also formed (Piotrowski 1984). 

Kyerematen GA, Taylor LH, deBethizy JD, Vesell ES (1988a) Pharmacokinetics of nicotine and 12 metabolites in the rat. Application of a new radiometric high performance liquid chromatography assay. Drug Metab Dispos 16 125-129... 

Larsen, G. L. Bakke, J. E. The Effect of Antibiotic Treatment on the Metabolism and Enterohepatic Circulation of Propachlor Metabolites in the Rat, unpublished. 

Elovaara, E., Engstrom, K., Riihimaki, V. Aitio, A. (1990) Kinetics of ethylberrzene and its metabolites in the rat. In International Workshop on Pharmacokinetic Modelling in Occupational Health, Leysin, Switzerland, March 4-8, Lausarme, Switzerland, Irrstitute of Occupational Health Sciences, pp. 52-53... 

Kirk, L.K., Lewis, B. A.. Ross. D.A. Morrison, M.A. (1987) Identification of ninhydrin-positive caprolactam metabolites in the rat. Food chem. Toxicol., 25, 233-239... 

Soderlund, E., Brunborg, G., Dybing, E., Trygg, B., Nelson, S.D. Holme, J.A. (1992) Organ-specific DNA damage of tris(2,3-dibromopropyl)phosphate and its diester metabolite in the rat. Chem.-biol. Interact., 82, 195-207... 

Urinary excretion profiles were measured for TDG, TDGO, and 3-lyase metabolites in the rat after percutaneous administration (10). Levels of TDG increased up to 10-fold by treatment of the urine... 

Schlede E, Kuntzman R, Conney AH. 1970. Stimulatory effect of benzo(a)-pyrene and phenobarbital pretreatment on the biliary excretion of benzo(a)pyrene metabolites in the rat. Cancer Res. 30 2898-904... 

The principal route of PBO degradation proceeds via an Initial oxidation and hydrolysis at the position of the ethoxy ethoxybutoxy side chain leading to the formation of MDB alcohol, also referred to as piperonyl alcohol. This undergoes further oxidation, through MDB aldehyde, to MDB acid. This acid, also referred to as pipcnunylic acid (Kamienski and Casida, 1970). was detected as a metabolite in the urine of mice, either as the free acid or conjugated. It has also been confirmed as a metabolite in the rat (Lin and Selim, 1991 Selim, 1991), where it accounted for c. 3% of the applied dose in both urine and faeces. 

The ll-palm-A -THC can be hydrolyzed to II-OH-A -thc by cholesterol esterase and triacylglycerol lipase but not by phospholipase A, acetylesterase or phosphotransacetylase (16). An attempt to modify the retention of fatty acid-conjugated DDT metabolites was carried out by injecting the DDT-treated rats with sodium salt of various bile acids, heparin or lecithin of which all were known to affect the esterification or ester hydrolysis by the cholesterol esterase system. The results Indicated a significant decrease in the retention of the conjugated DDT metabolites in the rat liver and spleen (17). 

Roth S, Park SS, Sikorski CW, Osinski J, Chan R, et al. 1997. Concentrations of adenosine and its metabolites in the rat retina/choroid during reperfusion after ischemia. Curr Eye Res 16 875-885. 

Chaparral has also been associated with cystic renal disease in rats (Grice et al., 1968 Goodman et al., 1970 Evan et al., 1979) and humans (Smith et al., 1994 see Section 16.5). Toxicity studies revealed that cystic nephropathy could be reliably induced in rats fed a 2% by wt concentration of NDGA for 6 wk (Evan et al., 1979). Renal toxicity may stem from the accumulation of theo-quinone metabolite. NDGA is converted to this metabolite in the rat ileum and cecum, absorbed into the bloodstream, and excreted by the kidney, where it is reabsorbed by the epithelial cells of the proximal convoluted tubules. In the rat, tubular changes are thus confined to the tubules in the outer cortex (i.e., the proximal convoluted tubules) (Grice et al., 1968). 

Povey AC, Brouet I, Bartsch H. 1987. Binding of benzo[a]pyrene metabolites in the rat intestinal lumen by magnetic polyethyleneimine microcapsules following an intragastric dose of [14C]benzo[a]pyrene. Carcinogenesis 8 825-831. 

Table II. Mass Balance and Distribution of Ametryn and Its Metabolites in the Rat, Lactating Goat, and Laying Hen...

Mason, G., and S. Safe. 1986. Synthesis, biologic and toxic effects of the major 2,3,7,8-tetrachloro-dibenzo-p-dioxin metabolites in the rat. Toxicology 41 2) 163-69. 

Shephard, R. M., Deluca, H. E. 1980. Plasma concentrations of vitamin D3 and its metabolites in the rat as influenced by vitamin D3 or 25-hydroxyvitamin D3 intakes. Arch Biochem Biophys, 202 43-53. 

Webb M, Samarawickrama GP (1981) Placental transport and embryonic utilization of essential metabolites in the rat at the teratogenic dose of cadmium. J. Appl. Toxicol. 1 270-277... 

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