- Email: [email protected]
Effect of magnesium pretreatment on glutathione levels in kidney and liver of mice exposed to acute cadmium intoxication
S198
Abstracts / Toxicology Letters 164S (2006) S1–S324
osteoblast-like cells were exposed to controlled speciations of Pb. The six most relevant Pb speciations, namely the most probable forms of the toxic in contact with cells after blood contamination, were selected for cell exposures. Pb was either complexed with phosphate (PbHPO4 ), bicarbonate (PbCO3 ), citrate (PbCIT), cysteine (PbCYST), albumin (PbAlbumin) or left free in the exposure medium (Pb* ). For each chemical state, Pb toxicity was assessed using the MTT assay. Results show that PbHCO3 , Pb* and PbCIT induce a significant toxicity to bone cells with the cytotoxicity index CI50 defined as Pb concentration leading to 50% cell death after 24 h exposure determined, respectively, at 25, 100 and 130 M. A concentration-dependant cytotoxicity was shown after 24 h exposure to PbCYST, however its toxicity never exceeded 50% cell death. On the opposite, PbHPO4 or PbAlbumin did not demonstrate toxicity to ROS17/2.8 osteoblast-like cells. In order to explain this difference of sensitivity between Pb species, cellular accumulations were quantified according to concentration, then to time, at lethal or sub-lethal doses (ICP-MS analyses of digested cell pellets). A correlation between toxicity and cellular accumulation could be evidenced. Finally, Pb repartition at the cell scale was characterized by SEM-EDS and PIXE. Precipitation phenomena could be observed inside and outside cells. These results stress the importance of a strictly controlled speciation of the metals in toxicology studies. doi:10.1016/j.toxlet.2006.07.069 P14-25 Effect of magnesium pretreatment on glutathione levels in kidney and liver of mice exposed to acute cadmium intoxication ´ c 1 , Milica Danijela Djuki´c-Cosi´ 2 Maliˇcevi´c , Vesna Matovi´c 1
ˇ Ninkovi´c 2 , Zivorad
1 Institute
of Toxicological Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia and Montenegro; 2 Institute of Medical Research, Military Medical Academy, Belgrade, Serbia and Montenegro Among numerous mechanisms proposed for Cd toxicity are oxidative stress and disturbances in metabolism and function of bioelements. Up-to-date investigations indicate that cadmium can decrease intracellular glutathione content and activities of cellular antioxidant enzymes, which lead to the accumulation of reactive oxygen species and an increase in intracellular oxidative stress.
It is well known that GSH plays a crucial role in intracellular protection against metals, e.g. Cd. Glutathione can act both as an antioxidant (scavenger of intracellular reactive oxygen species by a direct reaction, or via the GSH peroxidase/GSH system) and as a metal-chelating agent. On the other hand, investigations on interaction between Cd and bioelements indicate that excessive intake of bioelements, particularly magnesium, may antagonize cadmium effects. The objective of the study was to determine the effect of increased oral magnesium pretreatment on reduced GSH levels in kidney and liver of mice exposed to acute Cd intoxication. Swiss albino male mice were divided into four groups: I—control group, not treated animals; II—Cd group, animals given single oral dose of 20 mg Cd/kg b.w. as aqueous solution of CdCl2 ; III—Mg + Cd group, i.e. mice given orally 40 Mg/kg b.w. as aqueous solution of Mg(CH3 COO)2 1 h before Cd intoxication; IV–Mg group, animals given orally 40 Mg/kg b.w. as aqueous solution of Mg(CH3 COO)2 . The animals were sacrificed by decapitation at 4, 6, 12, 24 and 48 h and GSH content was determined in investigated organs. The obtained results show that acute Cd intoxication induced significantly increased GSH content in kidney after 12 and 24 h. On the other hand, statistically significant decrease of GSH content was observed in liver 4, 6 and 12 h after single oral Cd administration. Beneficial effects of Mg pretreatment on GSH content was observed partly; Mg pretreatment reduced the observed changes of GSH content in liver after 6 and 12 h and in kidney after 12 h. These results contribute to our investigations on interaction between cadmium and magnesium. doi:10.1016/j.toxlet.2006.07.070 P14-26 URANIUM (VI) toxicity after acute exposure of cultured renal cells: Citrate increases bioavailability and toxicity M. Carri`ere, C. Thiebault, S. Milgram, B. Gouget Laboratoire Pierre S¨ue, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette, France Uranium is a natural heavy metal, widely present in the environment. Its use in the nuclear industry and for military applications has raised concerns about its potential toxicity for populations and environment. Contamination can occur by ingestion of contaminated food or water, inhalation or through a wound. The metal rapidly transfers to target organs: kidneys, particularly proximal
Abstracts / Toxicology Letters 164S (2006) S1–S324
osteoblast-like cells were exposed to controlled speciations of Pb. The six most relevant Pb speciations, namely the most probable forms of the toxic in contact with cells after blood contamination, were selected for cell exposures. Pb was either complexed with phosphate (PbHPO4 ), bicarbonate (PbCO3 ), citrate (PbCIT), cysteine (PbCYST), albumin (PbAlbumin) or left free in the exposure medium (Pb* ). For each chemical state, Pb toxicity was assessed using the MTT assay. Results show that PbHCO3 , Pb* and PbCIT induce a significant toxicity to bone cells with the cytotoxicity index CI50 defined as Pb concentration leading to 50% cell death after 24 h exposure determined, respectively, at 25, 100 and 130 M. A concentration-dependant cytotoxicity was shown after 24 h exposure to PbCYST, however its toxicity never exceeded 50% cell death. On the opposite, PbHPO4 or PbAlbumin did not demonstrate toxicity to ROS17/2.8 osteoblast-like cells. In order to explain this difference of sensitivity between Pb species, cellular accumulations were quantified according to concentration, then to time, at lethal or sub-lethal doses (ICP-MS analyses of digested cell pellets). A correlation between toxicity and cellular accumulation could be evidenced. Finally, Pb repartition at the cell scale was characterized by SEM-EDS and PIXE. Precipitation phenomena could be observed inside and outside cells. These results stress the importance of a strictly controlled speciation of the metals in toxicology studies. doi:10.1016/j.toxlet.2006.07.069 P14-25 Effect of magnesium pretreatment on glutathione levels in kidney and liver of mice exposed to acute cadmium intoxication ´ c 1 , Milica Danijela Djuki´c-Cosi´ 2 Maliˇcevi´c , Vesna Matovi´c 1
ˇ Ninkovi´c 2 , Zivorad
1 Institute
of Toxicological Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia and Montenegro; 2 Institute of Medical Research, Military Medical Academy, Belgrade, Serbia and Montenegro Among numerous mechanisms proposed for Cd toxicity are oxidative stress and disturbances in metabolism and function of bioelements. Up-to-date investigations indicate that cadmium can decrease intracellular glutathione content and activities of cellular antioxidant enzymes, which lead to the accumulation of reactive oxygen species and an increase in intracellular oxidative stress.
It is well known that GSH plays a crucial role in intracellular protection against metals, e.g. Cd. Glutathione can act both as an antioxidant (scavenger of intracellular reactive oxygen species by a direct reaction, or via the GSH peroxidase/GSH system) and as a metal-chelating agent. On the other hand, investigations on interaction between Cd and bioelements indicate that excessive intake of bioelements, particularly magnesium, may antagonize cadmium effects. The objective of the study was to determine the effect of increased oral magnesium pretreatment on reduced GSH levels in kidney and liver of mice exposed to acute Cd intoxication. Swiss albino male mice were divided into four groups: I—control group, not treated animals; II—Cd group, animals given single oral dose of 20 mg Cd/kg b.w. as aqueous solution of CdCl2 ; III—Mg + Cd group, i.e. mice given orally 40 Mg/kg b.w. as aqueous solution of Mg(CH3 COO)2 1 h before Cd intoxication; IV–Mg group, animals given orally 40 Mg/kg b.w. as aqueous solution of Mg(CH3 COO)2 . The animals were sacrificed by decapitation at 4, 6, 12, 24 and 48 h and GSH content was determined in investigated organs. The obtained results show that acute Cd intoxication induced significantly increased GSH content in kidney after 12 and 24 h. On the other hand, statistically significant decrease of GSH content was observed in liver 4, 6 and 12 h after single oral Cd administration. Beneficial effects of Mg pretreatment on GSH content was observed partly; Mg pretreatment reduced the observed changes of GSH content in liver after 6 and 12 h and in kidney after 12 h. These results contribute to our investigations on interaction between cadmium and magnesium. doi:10.1016/j.toxlet.2006.07.070 P14-26 URANIUM (VI) toxicity after acute exposure of cultured renal cells: Citrate increases bioavailability and toxicity M. Carri`ere, C. Thiebault, S. Milgram, B. Gouget Laboratoire Pierre S¨ue, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette, France Uranium is a natural heavy metal, widely present in the environment. Its use in the nuclear industry and for military applications has raised concerns about its potential toxicity for populations and environment. Contamination can occur by ingestion of contaminated food or water, inhalation or through a wound. The metal rapidly transfers to target organs: kidneys, particularly proximal