metallothionein and nickel-chloride

The present research work was designed to study Dicentrarchus labrax biotransformation and detoxification responses to acute exposure to nickel (Ni) and chlorpyrifos (CHP). Sexually immature sea bass were treated by intraperitoneal injection of nickel chloride (500 μg kg⁻¹), chlorpyrifos (10 mg kg⁻¹), and their binary mixture for 1, 3, and 7 days. Ni and CHP accumulation was quantified in liver after the exposure periods. The following biological responses were measured: (1) NADPH cytochrome P450 reductase (NCR) activity, as phase I biotransformation parameter; (2) gluthathione S-transferase (GST) activity as a phase II conjugation enzyme, acetylcholinesterase activity, and metallothionein (MT) content. Ni bioaccumulation in the liver resulted in an increasing uptake up to 15.48 μg g⁻¹ wet weight (Ni-treated animals) and 16.73 μg g⁻¹ wet weight (mixture-treated animals) after 7 days of exposure. CHP accumulation showed a distinct pattern in animals exposed to the mixture of chemicals in comparison with CHP-treated animals. NCR activity exhibited a marked activation in CHP and mixture-treated animals. GST activity was significantly increased starting from 1 day exposure in CHP-treated animals and after 3 days in Ni-treated animals. MT accumulation increased in all conditions, with a marked synergetic effect after 7 days of exposure. These data should be carefully considered in view of the biological effects of mixture pollutants, particularly in fish farming conditions.

Topics: Acetylcholinesterase; Animals; Aquaculture; Bass; Chlorpyrifos; Glutathione Transferase; Liver; Metallothionein; NADPH-Ferrihemoprotein Reductase; Nickel; Water Pollutants, Chemical

Recent studies indicate that elasmobranch fish respond differently to metal exposure than marine teleosts. Accumulation rates can be high, which despite the fact that normal background levels for metals in the marine environment are low, is worrying due to the long life span and late fecundity of most shark. The goals of the present study were to examine differences in accumulation rates and toxicity of a range of metals at equimolar concentrations (10microM) in the Mediterranean or spotted dogfish, Scyliorhinus canicula. For this purpose, we exposed the dogfish to Ni (587microg/L), Cd (1124microg/L), Pb (2072microg/L), Cu (635microg/L), and Ag (1079microg/L and two additional exposures at 10microg/L and 1microg/L) for one week and measured total metal accumulation, metallothionein induction, and parameters related to osmoregulation. Our study confirms the high toxicity and accumulation rates of Ag for elasmobranch fish, even at levels 100 to 1000 times lower than exposure levels of other metals. Also Pb accumulated readily in all organs, but did not cause any osmoregulatory disturbance at the exposure levels used. Ni and Cd seem to accumulate primarily in the kidney while Cu mainly accumulated in liver. In contrast to Ni and Cd, the three other metals Ag, Cu and Pb accumulated in the rectal gland, an important organ for osmoregulation and possible target organ for metal toxicity. Only Cu succeeded in initiating a protective response by inducing MT synthesis in liver and gills.

Topics: Animals; Body Burden; Cadmium Compounds; Copper; Dogfish; Fish Proteins; Lead; Metallothionein; Metals; Nickel; Nitrates; Silver Nitrate; Time Factors; Tissue Distribution; Up-Regulation; Water Pollutants, Chemical; Water-Electrolyte Balance

Toxic metal ions have been implicated in the generation of reactive oxygen species (ROS) and nitric oxide (NO). Metallothionines (MT) and plant flavonoids have been reported in the intervention against oxidative damage. We investigated the effect of zinc induced MT and green tea polyphenol (GTP) in reducing the oxidative responses induced by nickel and platinum.. Zinc (10 mg/kg b. wt, sc) was administered to rats twice at a gap of 24 hrs and GTP (10 mg/100 mL in drinking water) was fed ad libitum for 8 days. Nickel chloride (150 umol/kgb.wt, ip) and cisplatin (50 mumol/kg b.wt, sc) was administered to rats 24 h after Zn or GTP pre-treatment. Animals of all the groups were sacrificed 16 hrs after treatment and biochemical markers for toxicity were monitored.. Zinc or GTP pre-treatment caused significant protection against nickel or cisplatin enhanced mortality in rats, and reduction in lipid peroxidation and NO.. It is proposed that inhibition of ROS and NO by GTP and zinc may prove useful as a selective pharmacological agent in the amelioration of metal toxicity.

Topics: Animals; Antioxidants; Biomarkers; Cisplatin; Flavonoids; Free Radical Scavengers; Lipid Peroxidation; Metallothionein; Mortality; Nickel; Nitric Oxide; Phenols; Polyphenols; Rats; Tea; Time Factors; Zinc

Recent studies have focussed on the role of thiol rich proteins especially metallothionein (MT) in the therapeutic interventions against oxidative damage. In our previous communication we showed that reactive oxygen species arising via Fenton's reactions are the proximal lipid oxidant during nickel-toxicity. The purpose of the present communication is to evaluate the role of zinc, cadmium or silver-metallothioneins on the protection against nickel-induced peroxidative damage. Our results demonstrate that Zn-MT provided maximum protection against nickel-induced mortality in mice and also served as an efficient antagonist in inhibiting nickel-mediated lipid peroxidation compared to Cd-MT or Ag-MT. Zn-MT also provided protection against iron (II)-ascorbate induced microsomal lipid peroxidation and reversed nickel-mediated inhibition of calcium sequenstration. We conclude that Zn-MT could serve as an excellent physiological antioxidant against nickel-mediated oxidative.

Topics: Animals; Ascorbic Acid; Cadmium; Cadmium Chloride; Chlorides; Drug Interactions; Ferric Compounds; Glutathione; Kinetics; Lipid Peroxidation; Metallothionein; Mice; Microsomes, Liver; Nickel; Silver Nitrate; Sulfates; Time Factors; Zinc; Zinc Sulfate

The nature of hepatic metallothionein (MT) induction by several metals and its relationship to an inflammatory response was studied in chicks. Intraperitoneal (ip) injection of chromium (Cr), managanese, and iron (Fe) caused a much greater increase in hepatic MT (10.2-, 9.0-, and 6.8-fold) compared with cobalt and nickel (2.5- and 2.9-fold); thus not all transition metals are effective. Cr3+ caused markedly greater hepatic MT accumulation than Cr6+, suggesting that the ionic nature of the metal is an important factor. Small organic complexes of Fe (ferrous gluconate or lactate, 6.2-fold) caused significantly greater accumulation of hepatic MT than ferric dextran (1.4-fold), a large organic aggregate. In vitro data from chick hepatocytes and/or fibroblasts clearly indicated that Fe does not effect the induction of MT directly. The role of inflammation, as measured by recruitment of peritoneal exudate cells (PEC), was examined. Endotoxin (LPS), Sephadex (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S = Fe greater than LPS much greater than control). The percentage of heterophils but not macrophages was significantly correlated with the accumulation and induction of hepatic MT. In a similar experiment with Cr, we demonstrated that Cr3+ but not Cr6+ stimulated MT messenger RNA accumulation and concomitant hetereophil infiltration at 3 h after injection. Our results indicate that the induction of hepatic MT by the parenteral administration of a number of metals is dependent on the chemical nature of the metal and is associated with an inflammatory response.

Topics: Animals; Cells, Cultured; Chick Embryo; Chickens; Chlorides; Chromium; Chromium Compounds; Cobalt; Ferric Compounds; Fibroblasts; Inflammation; Injections, Intraperitoneal; Kinetics; Liver; Male; Manganese Compounds; Manganese Poisoning; Metallothionein; Metals; Nickel

Topics: Animals; Cadmium Poisoning; Female; Kidney; Metallothionein; Nickel; Rats