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Arsenite exerts transgenerational reproduction defects in Caenorhabditis elegans
Abstracts / Toxicology Letters 238S (2015) S56–S383
P13-008 Aluminum and brain transaminase activity P. Omarkharoubi 1,∗ , A. Benyamina 2 1 2
University Usto, Biotechnology, Oran, Algeria University Usto, Biology, Oran, Algeria
Background: The biological and chemical properties of aluminum render maximum use of this metal in our everyday living. The toxicity of aluminum is now well established (Yosra BelaïdNouira et al., 2012). The brain is the most sensitive organ to show aluminum-induced dysfunctionment and several product of free radical (Yu et al., 2014). There are suggestions that glutamate can be involved in the aluminum-induced neurocomplications. The excitotoxic effect of glutamate is believed to be the cause of several neurodegenerative processes (Nayak and Chatterjee, 2002) and several enzymes with the capacity to regulate glutamate metabolism and protect brain from aluminum-induced neurotoxicity was suggested. Thus the study of glutamate metabolizing enzymes in brain of rats exposed to aluminum and received vitamin E at 200 mg/L in drinking water may be of importance for understanding the neuroprotective properties of antioxidant components on aluminium toxicity. Results: The groups treated by aluminum have a significant considerable reduction of metabolism and in the capacity antioxidant of whole brain. The interaction of aluminum intoxication and vitamin E supplementation show a significant increased activity in cases of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase of brain than the non-treated group. Conclusion: The response to aluminum exposure induced altered activities of specific transaminases of brain. This alteration was remaining normal by vitamin E administration; this effect is mainly probably due to antioxidant capacity of vitamin E and by the return to normal metabolism. http://dx.doi.org/10.1016/j.toxlet.2015.08.797
P13-009 The binding of antimony and hemoglobin as a basis for the accumulation of antimony in blood Z. Wu National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, The Toxicology Laboratory, Beijing, China Antimony (Sb) compounds are considered as possibly human carcinogens by International Agency for Research on Cancer. Though the metabolic process of antimony compound is not clear, some epidemiological investigation and animal experiments suggested that antimony could be accumulated in blood. However, very little is known about the interaction of antimony and the proteins in blood. Hemoglobin (Hb) was regarded as a possible target protein binding to antimony in blood. The sulfhydryl groups in cysteine of Hb could be as the reactive binding sites. In this study, we investigated the binding affinity of antimony compounds and Hb by using three system, pure Hb, red blood cells, and rats treated with antimony compounds in an acute exposure by tail vein injection. Methods: (1) Hb incubated with Sb. Hb (20 M) were incubated with antimony potassium tartrate (APTIII ) or potassium pyroantimonate (PPV ) (0–500 M) in25 mM ammonium acetate (pH 7.0) at room temperature for 24 h. After the reaction, the mixtures were subjected to the Sephadex desalting columns to separate
S277
the protein-bound antimony for ICPMS analysis. (2) RBCs incubated with Sb. Suspensions of the rat RBC and human RBC (10%) in PBS were separately incubated with APTIII or PPV (0, 200, 500 and 1000 mol/L) for 24 h at 37 ◦ C. After incubation, the cells were collected and subjected to lysis by adding water. The lysate was further centrifugation. The supernatant was analyzed for protein-bound antimony by using the Sephadex desalting columns separation and ICPMS. (3) Rats treated with Sb. Fifteen male Wistar rats were randomized into three groups of five each. The treatment groups were given APTIII or PPV , respectively, by tail vein injection one time at dose of 0.242 mg Sb/kg body weight. The control group was given physiological saline. After 1, 4, 24 and 48 h exposure, 5 rats of each group were gotten 0.5 ml blood into tubes containing lithium heparin. The RBC (10 L) were lysed and the supernatant solution was analyzed for Hb-bound antimony by using the Sephadex desalting columns separation and ICPMS. Results: Our study suggested that the binding affinity of antimony compounds for Hb by using pure Hb or RBCs in vitro was much weaker than that observed in vivo. This indicated that the metabolites of antimony are more likely the form bound to Hb, compared with the original antimony compound. A continuous and significant increase of Hb-bound antimony in the blood of rat treated with APTIII was observed, which could be a basis for the accumulation of antimony in blood. http://dx.doi.org/10.1016/j.toxlet.2015.08.798
P13-010 Arsenite exerts transgenerational reproduction defects in Caenorhabditis elegans V. Liao ∗ , C.-W. Yu National Taiwan University, Taipei, Taiwan Background: Arsenic permeates the environment and human beings are continuously exposed to it. However, the study on whether arsenic-induced toxicities can be transferred from parents to offsprings has received little attention. This study investigated the transgenerational reproduction defects by arsenic exposure in Caenorhabditis elegans. Principal findings: The results showed that the brood size of the C. elegans was significantly reduced in the parental generation (P0) by arsenic exposure, and the reduction of the brood size was also observed in the offspring generations, from F1 to F4. In addition, F1 generation accumulated arsenic when P0 generation was exposed to arsenic. Moreover, the mRNA levels of the vitellogenin genes, vit-2 and vit-6, were significant reduced in P0 by arsenic exposure. Likewise, the genes expression levels of vit-2 and vit-6 were also significantly reduced in F1 generation. Conclusions: Our study suggests that prenatal arsenic exposure causes transgenerational reproduction defects in C. elegans which might be attributed to arsenic accumulation and the reduction of the mRNA levels of the vitellogenin genes, vit-2 and vit-6. http://dx.doi.org/10.1016/j.toxlet.2015.08.799
P13-008 Aluminum and brain transaminase activity P. Omarkharoubi 1,∗ , A. Benyamina 2 1 2
University Usto, Biotechnology, Oran, Algeria University Usto, Biology, Oran, Algeria
Background: The biological and chemical properties of aluminum render maximum use of this metal in our everyday living. The toxicity of aluminum is now well established (Yosra BelaïdNouira et al., 2012). The brain is the most sensitive organ to show aluminum-induced dysfunctionment and several product of free radical (Yu et al., 2014). There are suggestions that glutamate can be involved in the aluminum-induced neurocomplications. The excitotoxic effect of glutamate is believed to be the cause of several neurodegenerative processes (Nayak and Chatterjee, 2002) and several enzymes with the capacity to regulate glutamate metabolism and protect brain from aluminum-induced neurotoxicity was suggested. Thus the study of glutamate metabolizing enzymes in brain of rats exposed to aluminum and received vitamin E at 200 mg/L in drinking water may be of importance for understanding the neuroprotective properties of antioxidant components on aluminium toxicity. Results: The groups treated by aluminum have a significant considerable reduction of metabolism and in the capacity antioxidant of whole brain. The interaction of aluminum intoxication and vitamin E supplementation show a significant increased activity in cases of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase of brain than the non-treated group. Conclusion: The response to aluminum exposure induced altered activities of specific transaminases of brain. This alteration was remaining normal by vitamin E administration; this effect is mainly probably due to antioxidant capacity of vitamin E and by the return to normal metabolism. http://dx.doi.org/10.1016/j.toxlet.2015.08.797
P13-009 The binding of antimony and hemoglobin as a basis for the accumulation of antimony in blood Z. Wu National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, The Toxicology Laboratory, Beijing, China Antimony (Sb) compounds are considered as possibly human carcinogens by International Agency for Research on Cancer. Though the metabolic process of antimony compound is not clear, some epidemiological investigation and animal experiments suggested that antimony could be accumulated in blood. However, very little is known about the interaction of antimony and the proteins in blood. Hemoglobin (Hb) was regarded as a possible target protein binding to antimony in blood. The sulfhydryl groups in cysteine of Hb could be as the reactive binding sites. In this study, we investigated the binding affinity of antimony compounds and Hb by using three system, pure Hb, red blood cells, and rats treated with antimony compounds in an acute exposure by tail vein injection. Methods: (1) Hb incubated with Sb. Hb (20 M) were incubated with antimony potassium tartrate (APTIII ) or potassium pyroantimonate (PPV ) (0–500 M) in25 mM ammonium acetate (pH 7.0) at room temperature for 24 h. After the reaction, the mixtures were subjected to the Sephadex desalting columns to separate
S277
the protein-bound antimony for ICPMS analysis. (2) RBCs incubated with Sb. Suspensions of the rat RBC and human RBC (10%) in PBS were separately incubated with APTIII or PPV (0, 200, 500 and 1000 mol/L) for 24 h at 37 ◦ C. After incubation, the cells were collected and subjected to lysis by adding water. The lysate was further centrifugation. The supernatant was analyzed for protein-bound antimony by using the Sephadex desalting columns separation and ICPMS. (3) Rats treated with Sb. Fifteen male Wistar rats were randomized into three groups of five each. The treatment groups were given APTIII or PPV , respectively, by tail vein injection one time at dose of 0.242 mg Sb/kg body weight. The control group was given physiological saline. After 1, 4, 24 and 48 h exposure, 5 rats of each group were gotten 0.5 ml blood into tubes containing lithium heparin. The RBC (10 L) were lysed and the supernatant solution was analyzed for Hb-bound antimony by using the Sephadex desalting columns separation and ICPMS. Results: Our study suggested that the binding affinity of antimony compounds for Hb by using pure Hb or RBCs in vitro was much weaker than that observed in vivo. This indicated that the metabolites of antimony are more likely the form bound to Hb, compared with the original antimony compound. A continuous and significant increase of Hb-bound antimony in the blood of rat treated with APTIII was observed, which could be a basis for the accumulation of antimony in blood. http://dx.doi.org/10.1016/j.toxlet.2015.08.798
P13-010 Arsenite exerts transgenerational reproduction defects in Caenorhabditis elegans V. Liao ∗ , C.-W. Yu National Taiwan University, Taipei, Taiwan Background: Arsenic permeates the environment and human beings are continuously exposed to it. However, the study on whether arsenic-induced toxicities can be transferred from parents to offsprings has received little attention. This study investigated the transgenerational reproduction defects by arsenic exposure in Caenorhabditis elegans. Principal findings: The results showed that the brood size of the C. elegans was significantly reduced in the parental generation (P0) by arsenic exposure, and the reduction of the brood size was also observed in the offspring generations, from F1 to F4. In addition, F1 generation accumulated arsenic when P0 generation was exposed to arsenic. Moreover, the mRNA levels of the vitellogenin genes, vit-2 and vit-6, were significant reduced in P0 by arsenic exposure. Likewise, the genes expression levels of vit-2 and vit-6 were also significantly reduced in F1 generation. Conclusions: Our study suggests that prenatal arsenic exposure causes transgenerational reproduction defects in C. elegans which might be attributed to arsenic accumulation and the reduction of the mRNA levels of the vitellogenin genes, vit-2 and vit-6. http://dx.doi.org/10.1016/j.toxlet.2015.08.799