Metal-induced Toxicity Research Articles

P3G181 - Cellular and molecular responses of metal-induced toxicity

P3G181 - Cellular and molecular responses of metal-induced toxicity

Mechanisms for protection against copper toxicity

Essential transition metals such as copper, molybdenum, and zinc and nonessential metals like cadmium, mercury, and lead can be toxic at the cellular, tissue, and organ levels when present in excess. To avoid metal-induced toxicity most organisms use a redundant combination of metal-regulated import inhibition, sequestration, and enhanced export mechanisms. Combinations of these mechanisms are used to form detoxification pathways controlled through metal-binding proteins at transcriptional, translational, or enzymatic levels. In mammalian pathways copper is partially detoxified by sequestration in the metal-binding metallothioneins or export via the copper-translocating ATPases. Copper regulation of these two mechanisms is afforded by specific conformational changes induced in regulatory proteins on metal binding.

Biomarker Assessment of the Effects of Petroleum Refinery Contamination on Channel Catfish

A suite of biomarkers was used to evaluate acute (1- and 7-day) heavy metal-induced toxicity in channel catfish,Ictalurus punctatus,caged at an abandoned petroleum refinery and a noncontaminated reference site. Assays performed include indicators of metabolic, hematological, osmoregulatory, and genotoxic stress. Two cage designs were utilized to evaluate the importance of exposure routes: one allowing exclusive contact with the water column and the other allowing contact with water and sediments. Data collected at 1 and 7 days postexposure indicated that the experimental fish were stressed, having significant increases in blood glucose. After 7 days of exposure, two hemodynamic parameters, hemoglobin and δ-aminolevulinic acid dehydratase, were significantly increased. There were no significant differences observed in other parameters measured.

Cytosolic redistribution and enhanced accumulation of Cu in gill tissue of Littorina littorea as a result of Cd exposure

Metallothionein (MT) binds Cd and Cu with differential affinity. The stability constant of Cu-thioneine is approximately two orders of magnitude greater than that of Cd-thioneine. Thus, it may be expected that MT, induced by Cd exposure, may sequester cytosolic Cu in preference to Cd, resulting in a concomitant redistribution of the metal. In this study, two groups of the marine gastropod, Littorina littorea, were exposed to NTA-buffered seawater solutions, which contained equal free-ion activities of Cu but either low or high Cd free-ion activities. ICP-MS analyses of gill-tissue cytosols show an increase in the concentrations of both Cd and Cu upon exposure to high concentrations of Cd. SE-HPLC profiles indicate that Cd is accumulated in a Cd and Cu metal-binding-ligand pool that may contain MT. Furthermore, a redistribution of Cu to this pool from two low-molecular-weight ligand pools is evident. If these results are reflective of the in-vivo situation and Cu is being sequestered from essential Cu-containing enzymes, then MT induction by Cd intoxication may ultimately result in metal-induced toxicity brought about by cellular Cu deficiency.

Effect of heavy metals on cellular growth, metabolism and integrity of cultured Chinese hamster kidney cells.

The effects of CdCl2, Na2CrO4, NaAsO2 and NiSO4 on cultured Chinese hamster kidney cells were studied over a concentration range for 48 h. Release of lactate dehydrogenase, a parameter of cell viability, was not closely related to cell proliferation except for Na2CrO4. A better correlation was obtained between glucose consumption and lactate production, and cellular growth. When studying toxic effects of metals in cell-culture systems, metabolic parameters should be determined in addition to cell viability and cellular growth. The results indicate that Chinese hamster kidney cells in culture might be useful to study mechanisms of metal-induced toxicity.

Effect of cupric chloride on oxidative metabolism in the freshwater teleost, Tilapia mossambica

The freshwater teleost Tilapia mossambica was subjected to lethal ( 6.0 mg · liter −1 = LC 50 48 hr ) and sublethal (1.5 mg · liter −1 copper treatment for 1, 7, and 14 days. The whole animal oxygen consumption and the activity levels of succinate dehydrogenase and lactate dehydrogenase in liver and muscle were studied. The decrease in oxygen consumption and succinate dehydrogenase activity and significant increase in lactate dehydrogenase activity suggest that the stressed fish is meeting its energy requirements through anaerobic oxidation and these enzymes can be used as indicators in monitoring metal-induced toxicity in fish.