J. Xenobiot., Volume 1, Issue 1 (May 2011) – 8 articles

Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX) A2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP) is a major cause of acute liver failure in the Western world. We investigated whether TXA2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT) in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX) B2 antibodies (anti-TXB2) and a selective inhibitor of thromboxane (TX) synthase, benzylimidazole (BZI), were significantly hepatoprotective, while a selective thromboxane receptor (TPR) antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA2, TXB2, and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB2. According to our results, this protection is mediated, at least in part, through decreased production of TXB2 by liver fragments ex vivo. Full article

Adult Bufo maculatus was exposed to sublethal cadmium concentrations of 0.25, 0.50, 1.00 and 2.00 mg/L. The toxicant from which the cadmium concentrations were prepared was cadmium chloride (CdCl2.H2O). There were three replicate tanks per treatment and three individuals per tank including control groups. The hematologic alterations based on the examination of blood indices during the 28 days of exposure showed that total erythrocyte count (TEC), hematocrit (Hct) and hemoglobin (Hb) concentration decreased (P<0.05) relative to controls. The decline was concentration- dependent as concentration of cadmium increased. The decline in hemoglobin and hematocrit in the experimental organism could be due to a decrease in the synthesis or release of erythrocytes into the circulation or an increase in the rate of erythrocyte destruction inflicted by cadmium toxicity. There was significant (P<0.05) elevation in total leuko- leukocyte count (TLC) with increase in the concen- cyte concentration of cadmium. The increase in total leukocyte count observed in this study could be attributed to a stimulation of the immune system in response to tissue damage caused by cadmium toxicity. The study has shown that the exposure of the Bufo maculatus toad to cadmium can inflict alterations in the hematologic indices, which could induce unfavorable physiological changes in the amphibian, which may lead to death. There is, therefore, the need to protect amphibians in order to sustain the biodiversity in the Nigerian Niger Delta ecological zone. Full article

Salicylic acid-(SA) is a plant defense stimulator. Exogenous application of SA might influence the status of glutathione-(GSH). GSH activates and SA alters the expression of defense genes to modulate plant resistance against pathogens. The fate of GSH in a crop following SA treatment is largely unknown. The SA-induced profiles of free reduced-, free oxidized-(GSSG) and protein bound-(PSSG) glutathione in tomato crop following foliar treatment of transplant at 5.0-10.0 μg mL–1 were measured by liquid chromatography. Resistance to root-knot nematode, Meloidogyne incognita damaging tomato and crop performance were also evaluated. SA treatment at 5.0-10.0 μg mL–1 to tomato transplants increased GSH, GSSG and PSSG in plant leaf and root, more so in leaf, during crop growth and development. As the fruits ripened, GSH and PSSG increased and GSSG declined. SA reduced the root infection by M. incognita, nematode reproduction and thus, improved the resistance of tomato var. Pusa Ruby, but reduced crop growth and redox status. SA at 5.0 μg mL–1 improved yield and fruit quality. The study firstly linked SA with activation of glutathione metabolism and provided an additional dimension to the mechanism of induced resistance against obligate nematode pathogen. SA increased glutathione status in tomato crop, imparted resistance against M. incognita, augmented crop yield and functional food quality. SA can be applied at 5.0 μg mL–1 for metabolic engineering of tomato at transplanting to combine host-plant resistance and health benefits in formulating a strategic nematode management decision. Full article

The immunotoxicological effects of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/Fs) mixtures on Eisenia andrei earthworms have never been studied. In this work we investigated these effects both for in vitro and in vivo exposure, using the viability and the phagocytic activity of coelomocytes as immunological biomarkers and the flow cytometry was used for analysis. The in vitro exposure revealed a cytotoxic effect of PCDD/Fs mixture (C2) containing 50¥10-3 ng/mL of 2, 3, 7, 8-TCDD and an induction of the phagocytic capacity at the mixture (C1) containing 25¥10-3 ng/mL of 2, 3, 7, 8-TCDD. In the in vivo filter paper exposure, the immunocompetence of earthworms was assessed after 3 h-exposure to mixtures of PCDD/Fs at the levels of C1, C2, C3 and C4 containing about; 0.05, 0.3, 0.5 and 0.83 ng of 2, 3, 7, 8-TCDD/cm², respectively. Morphological observations showed an excessive secretion of mucus and body surface lesions in worms exposed to higher concentrations (C3 and C4), which revealed that these organisms were affected by PCDD/Fs either through skin and/or by feeding. The levels of the extruded cell yield decreased significantly at all the concentrations tested. However, the cell viability was shown to be unaffected by PCDD/Fs concentrations. It was also shown, that exposure to the highest PCDD/Fs concentrations; C2, C3 and C4 inhibited both phagocytic activity and efficiency. Full article

Cytochrome P450 enzymes (CYP) are a group of monooxygenases able to biotransform several kinds of xenobiotics including aflatoxin B1 (AFB1), a highly toxic mycotoxin. These enzymes have been widely studied in humans and others mammals, but there is not enough information in commercial poultry species about their biochemical characteristics or substrate specificity. The aim of the present study was to identify CYPs from avian liver microsomes with the use of prototype substrates specific for human CYP enzymes and AFB1. Biochemical characterization was carried out in vitro and biotransformation products were detected by high-performance liquid chromatography (HPLC). Enzymatic constants were calculated and comparisons between turkey, duck, quail and chicken activities were done. The results demonstrate the presence of four avian ortholog enzyme activities possibly related with a CYP1A1, CYP1A2, CYP2A6 (activity not previously identified) and CYP3A4 poultry orthologs, respectively. Large differences in enzyme kinetics specific for prototype substrates were found among the poultry species studied. Turkey liver microsomes had the highest affinity and catalytic rate for AFB1 whereas chicken enzymes had the lowest affinity and catalytic rate for the same substrate. Quail and duck microsomes showed intermediate values. These results correlate well with the known in vivo sensitivity for AFB1 except for the duck. A high correlation coefficient between 7-ethoxyresorufin-Odeethylase (EROD) and 7-methoxyresorufin- O-deethylase (MROD) activities was found in the four poultry species, suggesting that these two enzymatic activities might be carried out by the same enzyme. The results of the present study indicate that four prototype enzyme activities are present in poultry liver microsomes, possibly related with the presence of three CYP avian orthologs. More studies are needed in order to further characterize these enzymes. Full article

The identification and quantification of bisphenol A (BPA) in wastewater (WW) and wastewater sludge (WWS) is of major interest to assess the endocrine activity of treated effluent discharged into the environment. BPA is manufactured in high quantities fro its use in adhesives, powder paints, thermal paper and paper coatings among others. Due to the daily use of these products, high concentration of BPA was observed in WW and WWS. BPA was measured in samples from Urban Community of Quebec wastewater treatment plant located in Quebec (Canada) using LC-MS/MS method. The results showed that BPA was present in significant quantities (0.07 μg L–1 to 1.68 μg L–1 in wastewater and 0.104 μg g–1 to 0.312 μg g–1 in wastewater sludge) in the wastewater treatment plant (WWTP). The treatment plant is efficient (76 %) in removal of pollutant from process stream, however, environmentally significant concentrations of 0.41 μg L–1 were still present in the treated effluent. Rheological study established the partitioning of BPA within the treatment plant. This serves as the base to judge the portion of the process stream requiring more treatment for degradation of BPA and also in selection of different treatment methods. Higher BPA concentration was observed in primary and secondary sludge solids (0.36 and 0.24 μg g–1, respectively) as compared to their liquid counterpart (0.27 and 0.15 μg L–1, respectively) separated by centrifugation. Thus, BPA was present in significant concentrations in the WWTP and mostly partitioned in the solid fraction of sludge (Partition coefficient (Kd) for primary, secondary and mixed sludge was 0.013, 0.015 and 0.012, respectively). Full article

Aerobic biodegradation of linear alkylbenzene sulfonate (LAS) by LAS-utilizing bacteria (LUB) in the presence of other sources of carbon (glucose and soluble starch) was examined. Biodegradation of LAS was monitored as primary degradation in terms of half-life (t½) of the surfactant. Biodegradation of LAS by the individual LUB was slower in the presence of Glucose. Biodegradation of the surfactant by the various consortia of LUB was slower in the presence of the carbon sources: t½ increased to 3 days. The rates of biodegradation by the consortia can be ranked as: four-membered (t½=9 days) > three-membered (t½=9 to 13 days) > two-membered consortia (t½=10 to 15 days). Generally, degradation in the presence of the carbon sources was faster with the consortia than the individual species. Degradation of the surfactant by the LUB was generally fastest in the absence of additional carbon sources. The possible role of additional carbon sources in persistence of surfactant in water bodies and the application of the observation in management of LAS-containing-effluent is suggested. Full article

Human cytochrome P450 3A7 (CYP3A7) and cytochrome P450 3A4 (CYP3A4) are hepatic metabolising enzymes which participates in the biotransformation of endo- and exogenous substances in foetuses and neonates respectively. These CYP3A enzymes display an inverse relationship: CYP3A7 is the dominant enzyme in the foetal liver, whereas the expression of CYP3A4 is low. After parturition there is a shift in the expression, thus CYP3A7 is down regulated, while the level of CYP3A4 gradually increases and becomes the dominant metabolising CYP3A enzyme in the adult. The minipig is increasingly being used as a model for humans in biomedical studies, because of its many similarities with the human physiology and anatomy. The aim of this study was to examine whether, as in humans, a shift is seen in the hepatic expression of a CYP3A7- like enzyme to cytochrome P450 3A29 (CYP3A29) (an orthologue to the human CYP3A4) in minipigs. This was elucidated by examining the hepatic mRNA expression of CYP3A7 and CYP3A29 in 39 foetuses and newborn Göttingen minipigs using quantitative real time polymerase chain reaction (qPCR). Furthermore the immunochemical level of CYP3A7-LE and CYP3A29 was measured in liver microsomes using western blotting. The expression of CYP3A29 was approximately 9- fold greater in neonates compared to foetuses, and a similar difference was reflected on the immunochemical level. It was not possible to detect a significant level of foetal CYP3A7 mRNA, but immunoblotting showed a visible difference depending on age. This study demonstrates an increase in the expression of CYP3A29, the CYP3A4 orthologue in perinatal minipigs as in humans, which suggests that the minipig could be a good model when testing for human foetal toxicity towards CYP3A4 substrates. Full article