Metabolism, bioavailability, and toxicokinetics of Benzo(α)pyrenein F-344 rats following oral administration

Ramesh, Aramandla; Inyang, Frank; Hood, Darryl B.; Archibong, Anthony E.; Knuckles, Maurice E.; Nyanda, Alfred M.

doi:10.1078/0940-2993-00192

Cited by 141 publications

(74 citation statements)

References 35 publications

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“…Indeed, the metabolite 3-OHBaP specifi cally was the focus of the study, whereas other metabolites are known to result from BaP biotransformation (Xue and Warshawsky, 2005). Furthermore, other organs such as reproductive organs, for instance, are known to capture important amounts of BaP because of their lipid contents but they were not included in our study since they were not primarily suspected of being responsible for 3-OHBaP body retention (Ramesh et al, 2001a).…”

Section: Discussionmentioning

confidence: 99%

A toxicokinetic study to elucidate 3‐hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats

Marie

Bouchard

Heredia-Ortiz

et al. 2010

J of Applied Toxicology

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The toxicokinetics of benzo(a)pyrene (BaP) and 3-hydroxybenzo(a)pyrene (3-OHBaP) were assessed in 36 male Sprague-Dawley rats injected intravenously with 40 micromol kg(1) of BaP to explain the reported atypical urinary excretion profile of 3-OHBaP. Blood, liver, kidney, lung, adipose tissue, skin, urine and feces were collected at t = 2, 4, 8, 16, 24, 33, 48, 72 h post-dosing. BaP and 3-OHBaP were measured by high-performance liquid chromatography/fluorescence. A biexponential elimination of BaP was observed in blood, liver, skin and kidney (t((1/2)) of 4.2-6.1 h and 12.3-14.9 h for initial and terminal phases, respectively), while a monoexponential elimination was found in adipose tissue and lung (t((1/2)) of 31.2 and 31.5 h, respectively). A biexponential elimination of 3-OHBaP was apparent in blood, liver and skin (t((1/2)) of 7.3-11.7 h and 15.6-17.8 h for initial and terminal phases, respectively), contrary to adipose tissue, lung and kidney. In adipose tissue and lung, a monophasic elimination of 3-OHBaP was observed (t((1/2)) of 27.0 h and 24.1 h, respectively). In kidney, 3-OHBaP kinetics showed a distinct pattern with an initial buildup during the first 8 h post-dosing followed by a gradual elimination (t((1/2)) of 15.6 h). In the 72-h post-treatment, 0.21 +/- 0.09% (mean +/- SD) of dose was excreted as 3-OHBaP in urine and 12.9 +/- 1.0% in feces while total BaP in feces represented 0.40 +/- 0.16% of dose. This study allowed the identification of the kidney as a retention compartment governing 3-OHBaP atypical urinary excretion.

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Section: Discussionmentioning

confidence: 99%

A toxicokinetic study to elucidate 3‐hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats

Marie

Bouchard

Heredia-Ortiz

et al. 2010

J of Applied Toxicology

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“…Tissue samples were extracted using a modified method of Willett et al (2000) and Ramesh et al (2001). Livers were collected from five animals each of the control and the BaP-exposed group, spleen and head kidneys from three trout per group.…”

Section: Methodsmentioning

confidence: 99%

“…Given the differences between liver, spleen, and head kidney in tissue structure, composition, and blood perfusion, we placed emphasis on comparing relative capacities for metabolite formation in the liver and immune tissues. Our analytical method was based on the methods of Ramesh et al (2001) and Beyer et al (2010) for determining the concentration of the target analyte by comparing retention times and peak areas of samples with that of standards. A dilution curve was prepared for each metabolite standard and BaP at concentrations between 0.1 and 8 ng/ml.…”

Section: Methodsmentioning

confidence: 99%

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

et al. 2013

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Polycyclic aromatic hydrocarbons (PAHs) are immunotoxicants in fish. In mammals, phase I metabolites are believed to be critically involved in the immunotoxicity of PAHs. This mechanism has been suggested for fish as well. The present study investigates the capacity of immune organs (head kidney, spleen) of rainbow trout, Oncorhynchus mykiss, to metabolize the prototypic PAH, benzo [a]pyrene (BaP). To this end, we analyzed 1) the induction of enzymatic capacity measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in immune organs compared with liver, 2) the organ profiles of BaP metabolites generated in vivo, and 3) rates of microsomal BaP metabolite production in vitro. All measurements were done for control fish and for fish treated with an intraperitoneal injection of 15 mg BaP/kg body weight. In exposed trout, the liver, head kidney, and spleen contained similar levels of BaP, whereas EROD induction differed significantly between the organs, with liver showing the highest induction factor (132.83), followed by head kidney (38.43) and spleen (1.43). Likewise, rates of microsomal metabolite formation experienced the highest induction in the liver of BaP-exposed trout, followed by the head kidney and spleen. Microsomes from control fish displayed tissue-specific differences in metabolite production. In contrast, in BaP-exposed trout, microsomes of all organs produced the potentially immunotoxic BaP-7,8-dihydrodiol as the main metabolite. The findings from this study show that PAHs, like BaP, are distributed into immune organs of fish and provide the first evidence that immune organs possess inducible PAH metabolism leading to in situ production of potentially immunotoxic PAH metabolites.

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“…Subsequently, the metabolites from the extracts were identified and measured by a reversephase HPLC equipped with a UV and a fluorescence detector as detailed in Ramesh et al (2001).…”

Section: Extraction and Analysis Of Tissues For Benzo(a)pyrene Metabomentioning

confidence: 99%

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Ramesh

Inyang

Lunstra

et al. 2008

Experimental and Toxicologic Pathology

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The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 rats to inhaled benzo(a)pyrene (BaP). Rats were assigned randomly to a treatment or control group. Treatment consisted of sub-chronic exposure of rats via inhalation to 75μg BaP/ m 3 , 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately after the cessation of exposures (time 0) and subsequently at 24, 48, and 72 hrs, to assess the effect of bioavailable BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Rats were sacrificed after the last blood collection. Testes were harvested, weighed and prepared for histology and morphometric analysis, and cauda epididymides were isolated for the determination of progressive motility and density of stored spermatozoa. BaP exposure reduced testis weight compared with UNC (Mean ± SE; 2.01 ± 0.11 vs. 3.04 ± 0.16 g; P< 0.025), and caused significant reductions in the components of the steroidogenic and spermatogenic compartments of the testis. Progressive motility and mean density of stored spermatozoa were reduced (P< 0.05). Plasma testosterone concentrations were decreased by two-thirds in BaPexposed rats throughout the time periods studied compared with those of their UNC counterparts (P< 0.05), concomitant with increased concentrations of LH in BaP-exposed rats (P< 0.05). These data suggest that sub-chronic exposure to inhaled BaP contribute to reduced testicular and epididymal function in exposed rats.

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Metabolism, bioavailability, and toxicokinetics of Benzo(α)pyrenein F-344 rats following oral administration

Cited by 141 publications

References 35 publications

A toxicokinetic study to elucidate 3‐hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats

A toxicokinetic study to elucidate 3‐hydroxybenzo(a)pyrene atypical urinary excretion profile following intravenous injection of benzo(a)pyrene in rats

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

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