Induction of metallothionein in chick embryos as a mechanism of tolerance to platinum group metal exposure.
Recent data show that platinum group metals (PGMs), primarily platinum (Pt), palladium (Pd) and rhodium (Rd), from automobile catalytic converters are being deposited in the environment. We investigated the PGM neurotoxicity and tolerance mechanism by induction of metallothionein (MT) in developing chick embryos. Chick embryos were injected on the 7th and 14th days of incubation with different concentrations of Pt and mixture of Pt, Pd and Rh (PGM mix) solutions. It is documented that induction of MT by zinc (Zn+2) protects against metal and non-metal hepatotoxicity. In this study the MT induction was examined through pretreatment of the two highest Pt(IV) exposure levels with exogenous Zn2+ on the 4th and 11th days of incubation. SDS-PAGE assay and digital image system were used to identify and quantify MT in homogenized brain and liver tissues. Quantitative analysis revealed an increase of MT in the 5 ppm Pt exposure as compared to controls. The 10 ppm Pt treatment was a lethal dose for exposed embryos. There was increased mortality at the 1.0 PGM mix level. The interaction of Pt, Pd and Rh in the mixture seems to favor metal accumulation and MT induction in the liver but not the brain. Pretreatment with exogenous Zn2+ increased chick survival. These results indicate that induction of MT plays a protective role against PGM toxicity. Metal analysis using atomic absorption spectrometer in graphite furnace mode (GFAAS) revealed PGM accumulation in chick embryo liver and brain tissues proportional to exposure concentration. Our results may imply that MT has an important role as a tolerance mechanism against PGM toxicity. The presence of Pt(IV) in brain tissue suggests that the undeveloped blood-brain barrier is permeable to PGMs. This raises concerns regarding the implication of these metals on neural injury.
Gagnon
Zofia E
ZE
School of Science, Marist College, Poughkeepsie, NY 12601, USA. Zofia.Gagnon@Marist.edu
Patel
Amit
A
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D004361:Drug Tolerance; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism*; D010165:Palladium / Q000494:pharmacology*; D010984:Platinum / Q000493:pharmacokinetics / Q000494:pharmacology*; D012238:Rhodium / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology
D010984:Platinum; D010165:Palladium; D008668:Metallothionein; D012238:Rhodium; D015032:Zinc