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Studies on the red grape extract supplementation against mercuric chloride induced toxicity in rat erythrocytes
Abstracts / Toxicology Letters 221S (2013) S59–S256
(24 h) significantly stimulated mRNA for RXRalpha (vs E2, COM, C), while profound inhibition (∼50%) was present after 72 and 96 h (vs C). 120 h BPA treatment elevated expression of RXRalpha back to values for 48 h. COM (BPA 10−12 M + E2: 10−12 /10−9 /10−6 M) immediately (24 h) reduced mRNA for RXRalpha (vs BPA, E2, C) and the inhibition persists for the next three days (vs BPA, C). ∼20–50% inhibition of RXRbeta gene expression was induced by BPA (10−6 M) and by COM (vs C) during 24, 48, 72 and 96 h treatment. Fast, 24 h BPA reducing effect relates RXRbeta gene, marked reduction of RXRalpha was present after 72 h. The BPA + E2 combination is more effective in reducing mRNA for RXRalpha then RXRbeta. Simultaneously BPA overstimulated CyclinD1 protein, the positive regulator of cell cycle progression. We hypothesize that reduced RXRalpha/beta genes underline impairment of respective receptor numbers, which could not function as mediators of growth inhibition. Thus BPA stimulated cell growth could result from reduced RXR genes and enhanced proteins involved in cell cycle. http://dx.doi.org/10.1016/j.toxlet.2013.05.185
P08-47 Selected organotin halides: Toxicity versus nuclear retinoic acid/retinoid X receptors and their co-regulators expression in breast cancer and leukemia cell lines Julius Brtko 1,∗ , Dana Macejova 1 , Lucia Bialesova 1 , Maria Fickova 1 , Viera Bohacova 2 , Zdena Sulova 3 , Albert Breier 4 , Luba Hunakova 5
S113
P08-48 Studies on the red grape extract supplementation against mercuric chloride induced toxicity in rat erythrocytes Kanti Bhooshan Pandey ∗ , Syed Ibrahim Rizvi Department of Biochemistry, University of Allahabad, Allahabad 211002, India Mercury is a well established highly toxic metal, exposure to which results in a variety of adverse health effects including neurological, renal, respiratory, immune and reproductive. Exposure to mercury cannot be avoided since its wide range of uses including industry, agriculture and medical. The study was aimed to evaluate the role of red grape extract supplementation in mercuric chloride induced toxicological biomolecular alterations in rats. Supplementation of red grape extract for intervening days orally resulted in decreased lipid peroxidation, erythrocyte membrane protein oxidation and significantly elevated plasma antioxidant capacity. Level of intracellular antioxidants; reduced glutathione, thiol groups and ascorbic acid which was reduced due to toxicology of mercury, were recovered in supplemented rats. Supplementation of grape extract also maintained the intracellular redox status in red blood cells as evidenced by the overexpressed PMRS. The results of the study demonstrate that red grape supplementation augments antioxidative defense mechanism in mercuric chloride induced toxicity and provides evidence that it may have a therapeutic role in metalinduced toxicological events. http://dx.doi.org/10.1016/j.toxlet.2013.05.187
IEE SAS, Bratislava, Slowakia, 2 UMPG SAS, Bratislava, Slowakia, 3 UMFG SAS, Bratislava, Slowakia, 4 FCHPT STU, Bratislava, Slowakia, 5 UEO SAS, Bratislava, Slowakia
1
Organotins represent a group of organic pollutants with potent endocrine-disrupting properties. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) were identified as nanomolar agonists for all types of nuclear retinoid X receptor (RXRalpha, RXRbeta, RXRgamma). The present study was undertaken to investigate (i) cytotoxicity of TBT-Cl, TPT-Cl, tributyltin bromide (TBT-Br), tributyltin iodide (TBT-I), and non-halide tributyltin hydride (TBT-H) in MCF-7 human breast cancer cell line and mouse leukemic L1210 cell lines (Pgp positive and Pgp negative); (ii) the effects of TBTCl, TBT-Br, TBT-I, TBT-H on the expression of nuclear all-trans retinoic acid receptors (RARalpha, RARgamma), retinoid X receptors (RXRalpha, RXRbeta), and their coregulators (SMRT, SRC-1). The IC50 values determined by MTT assay clearly have shown that TBT-Cl is more effective in inhibiting MCF-7 cell proliferation than TPT-Cl. Cytotoxicity of tested tributyltin compounds in MCF-7 cells was of the following order: TBT-Cl > TBT-Br > TBTI > TBT-H. In L1210 cell lines, IC50 pattern was ranging from 150 to 300 nmol/l, and the cytotoxicity of tributyltin compounds in Pgpnegative cells was in the order: TBT-I = TBT-H > TBT-Cl = TBT-Br, in Pgp-positive cells: TBT-Br = TBT-I > TBT-Cl = TBT-H. When compared to mock treated samples, the organotins tested (100 nM) in the presence of all-trans retinoic acid (10 M), a natural ligand for RARs, exerted significantly diminished RARs and RXRs expression pattern. The results suggest that these compounds may play an important role in modulation of retinoid receptors expression in MCF-7 cells. Supported by the APVV-0160-11, APVV-290-10, APVV147-10, APVV-SK-CZ-0211-11, 7AMB12SK151, VEGA-2/0008/11, and CEMAN grants. http://dx.doi.org/10.1016/j.toxlet.2013.05.186
P08-49 Study of platinum group metals effects on lettuce plants (Lactuca sativa) H. Mikulaskova, B. Nemcova, M. Beklova Department of Veterinary Ecology and Environmental Protection, University of Veterinary and Pharmaceutical Sciences, Palackeho 1-3, 612 42 Brno, Czech Republic The aim of this work was to assess ecotoxicity of PGMs platinum group metals (Pt, Pd, Rh), which are getting into the environment mainly from automobile traffic and to some extent also from hospital and industrial waste. A suitable bioindicator for testing harmful pollutants in soil is lettuce (Lactuca sativa). PGMs were added to the tested substrates in defined concentrations and its toxicity was estimated by measuring the root growth of lettuce seedlings (Lactuca sativa cv. Safır), the seedlings were recorded after incubation at 22 ◦ C in darkness for 5 days. The method was modified from ISO 11269. Based on the results, was observed that inhibitory effect of PGMs depend on the concentration increment. The value of the effective concentration (EC) PtCl4 , which causes 5% inhibition of growth compared to the control, after time period of 120 h, was 1.56 M and 120hEC50 was 40.93 M. The value of the (120hEC5) PdCl2 was 1.24 M, (120hEC50) was not found and the value of the (120hEC5) RhCl3 was 0.53 M, (120EC50) was not found. Comparing the obtained results it is possible tosay that the most sensitive reaction of lettuce on tested metals was in fallowing order RhCl3 → PdCl2 → PtCl4 . http://dx.doi.org/10.1016/j.toxlet.2013.05.188
(24 h) significantly stimulated mRNA for RXRalpha (vs E2, COM, C), while profound inhibition (∼50%) was present after 72 and 96 h (vs C). 120 h BPA treatment elevated expression of RXRalpha back to values for 48 h. COM (BPA 10−12 M + E2: 10−12 /10−9 /10−6 M) immediately (24 h) reduced mRNA for RXRalpha (vs BPA, E2, C) and the inhibition persists for the next three days (vs BPA, C). ∼20–50% inhibition of RXRbeta gene expression was induced by BPA (10−6 M) and by COM (vs C) during 24, 48, 72 and 96 h treatment. Fast, 24 h BPA reducing effect relates RXRbeta gene, marked reduction of RXRalpha was present after 72 h. The BPA + E2 combination is more effective in reducing mRNA for RXRalpha then RXRbeta. Simultaneously BPA overstimulated CyclinD1 protein, the positive regulator of cell cycle progression. We hypothesize that reduced RXRalpha/beta genes underline impairment of respective receptor numbers, which could not function as mediators of growth inhibition. Thus BPA stimulated cell growth could result from reduced RXR genes and enhanced proteins involved in cell cycle. http://dx.doi.org/10.1016/j.toxlet.2013.05.185
P08-47 Selected organotin halides: Toxicity versus nuclear retinoic acid/retinoid X receptors and their co-regulators expression in breast cancer and leukemia cell lines Julius Brtko 1,∗ , Dana Macejova 1 , Lucia Bialesova 1 , Maria Fickova 1 , Viera Bohacova 2 , Zdena Sulova 3 , Albert Breier 4 , Luba Hunakova 5
S113
P08-48 Studies on the red grape extract supplementation against mercuric chloride induced toxicity in rat erythrocytes Kanti Bhooshan Pandey ∗ , Syed Ibrahim Rizvi Department of Biochemistry, University of Allahabad, Allahabad 211002, India Mercury is a well established highly toxic metal, exposure to which results in a variety of adverse health effects including neurological, renal, respiratory, immune and reproductive. Exposure to mercury cannot be avoided since its wide range of uses including industry, agriculture and medical. The study was aimed to evaluate the role of red grape extract supplementation in mercuric chloride induced toxicological biomolecular alterations in rats. Supplementation of red grape extract for intervening days orally resulted in decreased lipid peroxidation, erythrocyte membrane protein oxidation and significantly elevated plasma antioxidant capacity. Level of intracellular antioxidants; reduced glutathione, thiol groups and ascorbic acid which was reduced due to toxicology of mercury, were recovered in supplemented rats. Supplementation of grape extract also maintained the intracellular redox status in red blood cells as evidenced by the overexpressed PMRS. The results of the study demonstrate that red grape supplementation augments antioxidative defense mechanism in mercuric chloride induced toxicity and provides evidence that it may have a therapeutic role in metalinduced toxicological events. http://dx.doi.org/10.1016/j.toxlet.2013.05.187
IEE SAS, Bratislava, Slowakia, 2 UMPG SAS, Bratislava, Slowakia, 3 UMFG SAS, Bratislava, Slowakia, 4 FCHPT STU, Bratislava, Slowakia, 5 UEO SAS, Bratislava, Slowakia
1
Organotins represent a group of organic pollutants with potent endocrine-disrupting properties. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) were identified as nanomolar agonists for all types of nuclear retinoid X receptor (RXRalpha, RXRbeta, RXRgamma). The present study was undertaken to investigate (i) cytotoxicity of TBT-Cl, TPT-Cl, tributyltin bromide (TBT-Br), tributyltin iodide (TBT-I), and non-halide tributyltin hydride (TBT-H) in MCF-7 human breast cancer cell line and mouse leukemic L1210 cell lines (Pgp positive and Pgp negative); (ii) the effects of TBTCl, TBT-Br, TBT-I, TBT-H on the expression of nuclear all-trans retinoic acid receptors (RARalpha, RARgamma), retinoid X receptors (RXRalpha, RXRbeta), and their coregulators (SMRT, SRC-1). The IC50 values determined by MTT assay clearly have shown that TBT-Cl is more effective in inhibiting MCF-7 cell proliferation than TPT-Cl. Cytotoxicity of tested tributyltin compounds in MCF-7 cells was of the following order: TBT-Cl > TBT-Br > TBTI > TBT-H. In L1210 cell lines, IC50 pattern was ranging from 150 to 300 nmol/l, and the cytotoxicity of tributyltin compounds in Pgpnegative cells was in the order: TBT-I = TBT-H > TBT-Cl = TBT-Br, in Pgp-positive cells: TBT-Br = TBT-I > TBT-Cl = TBT-H. When compared to mock treated samples, the organotins tested (100 nM) in the presence of all-trans retinoic acid (10 M), a natural ligand for RARs, exerted significantly diminished RARs and RXRs expression pattern. The results suggest that these compounds may play an important role in modulation of retinoid receptors expression in MCF-7 cells. Supported by the APVV-0160-11, APVV-290-10, APVV147-10, APVV-SK-CZ-0211-11, 7AMB12SK151, VEGA-2/0008/11, and CEMAN grants. http://dx.doi.org/10.1016/j.toxlet.2013.05.186
P08-49 Study of platinum group metals effects on lettuce plants (Lactuca sativa) H. Mikulaskova, B. Nemcova, M. Beklova Department of Veterinary Ecology and Environmental Protection, University of Veterinary and Pharmaceutical Sciences, Palackeho 1-3, 612 42 Brno, Czech Republic The aim of this work was to assess ecotoxicity of PGMs platinum group metals (Pt, Pd, Rh), which are getting into the environment mainly from automobile traffic and to some extent also from hospital and industrial waste. A suitable bioindicator for testing harmful pollutants in soil is lettuce (Lactuca sativa). PGMs were added to the tested substrates in defined concentrations and its toxicity was estimated by measuring the root growth of lettuce seedlings (Lactuca sativa cv. Safır), the seedlings were recorded after incubation at 22 ◦ C in darkness for 5 days. The method was modified from ISO 11269. Based on the results, was observed that inhibitory effect of PGMs depend on the concentration increment. The value of the effective concentration (EC) PtCl4 , which causes 5% inhibition of growth compared to the control, after time period of 120 h, was 1.56 M and 120hEC50 was 40.93 M. The value of the (120hEC5) PdCl2 was 1.24 M, (120hEC50) was not found and the value of the (120hEC5) RhCl3 was 0.53 M, (120EC50) was not found. Comparing the obtained results it is possible tosay that the most sensitive reaction of lettuce on tested metals was in fallowing order RhCl3 → PdCl2 → PtCl4 . http://dx.doi.org/10.1016/j.toxlet.2013.05.188