Comparison of the urinary excretion time courses of pyrene-1,6-dione, pyrene-1,8-dione and 1-hydroxypyrene in rats intravenously exposed to pyrene

Abstract

The urinary excretion time courses of pyrene-1,6-dione (P16D), pyrene-1,8-dione (P18D) and 1-hydroxypyrene (1-OHP) were compared in Sprague-Dawley and Wistar rats. Groups of five male rats, of about 200 g of body weight, were injected intravenously with 0.05, 0.5, 5 and 50 micromol pyrene kg-1 of body weight. Urine was collected at 2, 4, 6, 8, 10, 12, 18, 24, 30, 42 and 48 h post-dosing. Pyrene metabolites were measured by high-performance liquid chromatography (HPLC)/fluorescence after enzymatic hydrolysis of the glucurono- and sulfo-conjugates, extraction on Sep-Pak C18 cartridges and, for the analysis of dione metabolites, derivatization to stable diacetoxypyrene molecules. Over the 48-h sampling period, on average 17.4-25.6% of the injected pyrene was excreted overall as P16D, 6.4-8.8% as P18D and 0.6-0.8% as 1-OHP in the urine of Sprague-Dawley rats. By comparison, on average 10.3-14.7% of the intravenous pyrene dose was recovered as P16D, 4.8-6.4% as P18D and 0.3-0.4% as 1-OHP in the urine of Wistar rats. In both strains of rats there was no clear effect of the dose on the 0-48-h cumulative urinary excretion of P18D and 1-OHP over the entire dose range, while the percentage of dose recovered overall as P16D in urine at the highest dose (50 micromol kg-1) was statistically lower than at the other doses. The 0-48-h cumulative percentage of pyrene dose excreted as metabolites in the urine of Sprague-Dawley rats was also significantly higher than in Wistar rats (p<0.01) exposed under identical conditions. As for the urinary excretion-time courses of the different metabolites, for a given dose and strain of rats, excretion curves of P16D, P18D and 1-OHP generally evolved in parallel. There was also no clear effect of the dose on the excretion rate, thus half-life, of pyrene metabolites, except for P16D in Sprague-Dawley rats at the highest dose where elimination tended to be slower compared with the other doses (p<0.01). The average first-order elimination half-life of P16D, P18D and 1-OHP was 4.0, 5.7 and 4.1 h, respectively, in Sprague-Dawley rats, and 5.1, 6.1 and 5.1 h, respectively, in Wistar rats (all doses combined but excluding the highest dose for P16D). This study showed the relative importance of metabolic pathways leading to diones compared with 1-OHP. These dioxygenated metabolites appear to be interesting biomarkers of pyrene exposure at environmentally and occupationally relevant doses. Their adequacy as biomarkers of human exposure has yet to be confirmed.

1-Hydroxypyrene in Milk and Urine as a Bioindicator of Polycyclic Aromatic Hydrocarbon Exposure of Ruminants

“…It can also be reasonably assumed that other metabolites of pyrene, different from 1-OH-pyrene, represent a major source of pyrene metabolites as compared to 1-OH-pyrene. Whereas the first assumption is actually generally recognized in the literature, the second assumption can be supported by the recent studies of Ruzgyte et al , . These authors recently showed that about 27% of pyrene intravenously injected into Sprague–Dawley rats was metabolized under the pyrene-1,6-dione and pyrene-1,8-dione forms against about 1% only under the 1-OH-pyrene form (analysis in urine over a 48 h sampling period).…”

Analysis of pyrene metabolites in marine snails by liquid chromatography using fluorescence and mass spectrometry detection

“…This suggests that peak G represents an isomer of PYDS other than 1,6-PYDS, and therefore a novel biotransformation product. In all cases in the literature where pyrenediol or its conjugates were detected as metabolites of PY they were identified as either the 1,6 or the 1,8 isomers [10,11,51]. It is therefore likely that peak G represents 1,8-PYDS.…”

“…biotransformation products of pyrene have also been identified in other organisms, including humans [56], rats [51] and clams [29] but so far not in finfish.…”

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model

“…Other biotransformation products of 1-OHP that have been identified are 1,6-and 1,8-dioxygenated metabolites of pyrene. Ruzgyte et al (2005Ruzgyte et al ( , 2006 showed significant excretion of pyrene-1,6-and pyrene-1,8-dioxygenated metabolites in urine of rats after i.v. injection of pyrene.…”