Aksorn Saengtienchai

Concentrations and human health risk assessment of organochlorine pesticides in edible fish species from a Rift Valley lake—Lake Ziway, Ethiopia

Fish consumption is known to have several health benefits for humans. However, the accumulation of organic pollutants, like organochlorine pesticides (OCPs) could pose health hazards. Thus, OCPs in edible fish species (Oreochromis niloticus, Tilapia zillii, Carassius spp., and Clarias gariepinus) from Lake Ziway, an Ethiopian Rift Valley Lake were investigated to assess the potential human health hazards of these contaminants. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), chlordanes, and heptachlors were observed with ΣOCPs concentration ranging from 1.41 to 63.8 ng g(-1) ww. DDTs were the predominant contaminants (0.9 to 61.9 ng g(-1) ww), followed by HCHs. The predominance of DDTs may be attributed to their current use in vector control and contamination from past usage. The estimated daily intakes (EDIs) of OCPs from all fish species were much lower than the acceptable daily intakes (ADIs), indicating that consumption of fish is at little risk to human health at present. However, the cancer risk estimates in the area of concern and the hazard ratios (HRs) of HCHs, DDTs, and heptachlors exceeded the threshold value of one, indicating daily exposure to these compounds is a potential concern. This may result in a lifetime cancer risk greater than of 1 in 10(6).

Comparison of warfarin sensitivity between rat and bird species

Scattering coumarin derivative rodenticides in broad areas have caused primary- and secondary-poisoning incidents in non-target wild birds. In this study, we compared factors determining warfarin sensitivity between bird species and rats based on vitamin K 2,3-epoxide reductase (VKOR) kinetics, VKOR inhibition by warfarin and warfarin metabolism assays. In VKOR characterization, chickens and ostriches showed significantly lower enzymatic efficiencies than rats (one-sixth and one-third, respectively), suggesting bird species depend more on a non-VKOR vitamin K source. On the other hand, the inhibition constants (K(i)) of VKOR for warfarin were significantly different between chickens and ostriches (11.3+/-2.5 microM and 0.64+/-0.39 microM, respectively). Interestingly, the ostrich K(i) was similar to the values for rats (0.28+/-0.09 microM). The K(i) results reveal a surprising possibility that VKOR in some bird species are easily inhibited by warfarin. Warfarin metabolism assays also showed a large inter-species difference in bird species. Chickens and ostriches showed higher metabolic activity than that of rats, while mallards and owls showed only a slight ability to metabolize warfarin. In this study, we clarified the wide inter-species difference that exists among birds in xenobiotic metabolism and sensitivity to a rodenticide.

Characterization of phase-II conjugation reaction of polycyclic aromatic hydrocarbons in fish species: Unique pyrene metabolism and species specificity observed in fish species

Metabolic activity, particularly conjugation, was examined in fish by analyzing pyrene (a four-ring, polycyclic aromatic hydrocarbon) metabolites using high-performance liquid chromatography (HPLC) with fluorescence detector (FD), a mass spectrometry (MS) system, and kinetic analysis of conjugation enzymes. Fourteen fresh water fish species, including Danio rerio and Orizias latipes, were exposed to aqueous pyrene, and the resulting metabolites were collected. Identification of pyrene metabolites by HPLC/FD and ion-trap MS indicated that the major metabolites were pyrene glucuronide and pyrene sulfate in all 14 species. Differences were observed in pyrene glucuronide:pyrene sulfate ratio and in the total amount of pyrene conjugates excreted between fish species. Furthermore, a correlation was found between the amount of pyrene glucuronide present and the total amount of the pyrene metabolite eliminated. Kinetic analysis of conjugation by hepatic microsomes in vitro indicated that the differences in excreted metabolites reflected the differences in enzymatic activities.

Characterization and tissue distribution of conjugated metabolites of pyrene in the rat.

Pyrene (PY) is a polycyclic aromatic hydrocarbon (PAH) that is often used as a biomarker for human and wildlife exposure to PAHs. As the metabolites of PAHs, similar to their parent compounds, pose public health risks, it is necessary to study their characteristics and tissue-specific distribution. The present study was performed to experimentally characterize PY metabolites and analyze the tissue-specific distribution of the conjugated metabolites after oral administration of PY to rats. PY metabolites, such as pyrenediol-disulfate (PYdiol-diS), pyrenediol-sulfate (PYdiol-S), pyrene-1-sufate (PYOS), pyrene-1-glucuronide (PYOG) and 1-hydroxypyrene (PYOH), were detected in rat urine. Although glucuronide conjugate was the predominant metabolite, the metabolite composition varied among tissues. Interestingly, the proportion of PYOH was high in the large intestine. Furthermore, PYOH was the only PY metabolite detected in feces.

Monitoring Lead (Pb) Pollution and Identifying Pb Pollution Sources in Japan Using Stable Pb Isotope Analysis with Kidneys of Wild Rats

Although Japan has been considered to have little lead (Pb) pollution in modern times, the actual pollution situation is unclear. The present study aims to investigate the extent of Pb pollution and to identify the pollution sources in Japan using stable Pb isotope analysis with kidneys of wild rats. Wild brown (Rattus norvegicus, n = 43) and black (R. rattus, n = 98) rats were trapped from various sites in Japan. Mean Pb concentrations in the kidneys of rats from Okinawa (15.58 mg/kg, dry weight), Aichi (10.83), Niigata (10.62), Fukuoka (8.09), Ibaraki (5.06), Kyoto (4.58), Osaka (4.57), Kanagawa (3.42), and Tokyo (3.40) were above the threshold (2.50) for histological kidney changes. Similarly, compared with the previous report, it was regarded that even structural and functional kidney damage as well as neurotoxicity have spread among rats in Japan. Additionally, the possibility of human exposure to a high level of Pb was assumed. In regard to stable Pb isotope analysis, distinctive values of stable Pb isotope ratios (Pb-IRs) were detected in some kidney samples with Pb levels above 5.0 mg/kg. This result indicated that composite factors are involved in Pb pollution. However, the identification of a concrete pollution source has not been accomplished due to limited differences among previously reported values of Pb isotope composition in circulating Pb products. Namely, the current study established the limit of Pb isotope analysis for source identification. Further detailed research about monitoring Pb pollution in Japan and the demonstration of a novel method to identify Pb sources are needed.

Comparative metabolism of warfarin in rats and chickens

Warfarin, a coumarin rodenticide, is commonly used worldwide for rodent control, and is often reported as the cause for poisoning accidents in nontarget animals, in particular bird species. However, the metabolism of warfarin in birds is still unclear. In a previous study, we found an unknown warfarin metabolite in chicken cytosolic fractions. In the present study, we aimed to clarify the cytosolic warfarin metabolites in chickens compared with those in rats. The cytosol fractions of both chicken and rat livers showed the metabolic activity of 2 diastereomers and 2 enantiomers of warfarin alcohol. In chicken cytosol, we found that the production level of (S)-warfarin-(S)-alcohol was markedly higher (32-fold) than that in rat cytosol. From the results of the inhibition assay, we finally suggest that aldehyde oxidase may mainly contribute to the warfarin alcohol products in chicken cytosol.

Comparison of xenobiotic metabolism in phase I oxidation and phase II conjugation between rats and bird species

There have been many reports regarding toxic chemicals in birds. Chemicals are mainly metabolized in the liver through phase I oxidation by cytochrome P450 (CYP) and phase II conjugation by conjugated enzymes, such as UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), glutathione-S-transferase (GST), etc. Xenobiotic metabolism differs among bird species, but little detailed information is available. In the present study, the four-ring polycyclic aromatic hydrocarbon (PAH), pyrene, was used as a model xenobiotic to clarify the characteristics of xenobiotic metabolism in birds compared with laboratory animals by in vivo and in vitro studies. Plasma, bile, and excreta (urine and feces) were collected after oral administration of pyrene and analyzed to clarify xenobiotic metabolism ability in chickens and quails. Interestingly, pyrenediol-glucuronide sulfate (PYDOGS) and pyrenediol-diglucuronide (PYDOGG) were present in chickens and quails but not in rats. In addition, the area under the curve (AUC), maximum plasma concentration (Cmax), and time to maximum plasma concentration (Tmax) of pyrene-1-sulfate (PYOS) were higher than those of the parent molecule, pyrene, while the elimination half-life (t1/2) and mean residence time (MRT) were faster than those of the parent pyrene. With regard to sulfation of 1-hydroxypyrene (PYOH), the maximum velocity (Vmax) and Michaelis constant (Km) of rat liver cytosol were greater than those of chicken and quail liver cytosol. Furthermore, Vmax/Km of UGT activity in rat liver microsomes was also greater than those of chicken and quail liver microsomes. Characterization of xenobiotic metabolism revealed species differences between birds and mammals, raising concerns about exposure to various xenobiotics in the environment.

Sex and site differences in urinary excretion of conjugated pyrene metabolites in the West African Shorthorn cattle

Industrialization, economic and population growth rates in Ghana have increased the release of contaminants including polycyclic aromatic hydrocarbons (PAHs) into the environment through which humans and animals are exposed. Cattle is reported to be exposed to high levels of PAHs through feed and inhalation. Once exposed, PAHs are metabolized and excreted in urine, feces or bile. In a previous study, cattle in Ghana was reported to excrete high levels of 1-hydroxypyrene (1-OHPyr) due to high exposure to the parent compound, pyrene. 1-OHPyr is further metabolized to glucuronide and sulfate conjugates. Thus, the aim of this study was to investigate the sex and site differences in urinary excretion of conjugated pyrene metabolites using cattle urine collected from rural and urban sites of the Ashanti region, Ghana. From the results, geometric mean concentration adjusted by specific gravity indicated that 1-OHPyreneGlucuronide (PyG) was the most abundant conjugate followed by PyrenediolSulfate (M3). The sum of conjugated pyrene metabolites and sum of both conjugated and deconjugated pyrene metabolites correlated significantly with PyG, PydiolSulfate (M2) and PydiolSulfate (M3). The study revealed no significant difference in urinary excretion of conjugated pyrene metabolites between rural and urban sites. This indicated that similar to urban sites, cattle in rural sites were exposed to high levels of pyrene. There was no significant difference in urinary concentrations of conjugated pyrene metabolites between sexes.

Are red gourami (Colisa labiosa) low xenobiotic metabolizers? Elucidation of in vivo pharmacokinetics of pyrene as a model substrate

Red gourami (Colisa labiosa) have previously been shown to have low levels of pyrene-metabolizing activity. In this study, other pharmacokinetic factors of pyrene in C. labiosa were compared to those in Japanese medaka (Oryzias latipes). Results indicated that the two species labiosa absorbed pyrene in similar amounts. However, excretion of pyrene metabolites from C. labiosa over an 8-day period was lower than those from O. latipes. These findings show that C. labiosa has low ability to metabolize pyrene and to excrete pyrene and its metabolites from the body, and is therefore considered an accumulator of these chemicals. C. labiosa has unique characteristics with regard to pyrene pharmacokinetics. Knowledge about interspecies differences in pharmacokinetics is crucial in determining the endangered species to xenobiotic exposure.