Nickel di(acetate)

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for publication.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway

Author:

Wang YF, Shyu HW, Chang YC, Tseng WC, Huang YL, Lin KH, Chou MC, Liu HL, Chen CY.

Year:

2012

Bibliographic source:

Toxicology and Applied Pharmacology; 259:177-186

Materials and methods

Type of study / information:

Cell culture study to evaluate cytotoxicity and apoptosis.

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Human proximal tubule epithelial cells were treated with nickel acetate for up to 72 hours and then evaluated for the following: cell viability, colony formation, reactive oxygen species (ROS), DNA damage, mitochondrial membrane potential, apoptosis, cytochrome c concentration, and various protein levels.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Nickel di(acetate)

EC Number:

206-761-7

EC Name:

Nickel di(acetate)

Cas Number:

373-02-4

Molecular formula:

Ni(CH3CO2)2

IUPAC Name:

nickel di(acetate)

Specific details on test material used for the study:

As cited in paper: nickel (II) acetate

Results and discussion

Any other information on results incl. tables

Nickel-treated cells had significant reduction in cell viability in a concentration-dependent manner. Cell viability was less than 50% after 48 hours when the highest dose of nickel (480 uM) was used. Colony formation was suppressed by 50 -75% at all nickel concentrations as compared to control.

Nickel-treated cells had significant increase in DNA damage as observed from the comet assay. Intracellular ROS significantly increased after treatment for 48 hours. At the highest dose (480 uM) after 48 hours, a 208% increase was observed as measured by DCF fluourescent intensity.

Cell mitochondrial membrane potential (MMP) was reduced (as measured by reduced Rh123 staining) following nickel-treatment.

Nickel-treatment also increased apoptosis (as measured by the percent of cells in sub-G1 phase). Control had 2.15% and treated cells to 19.39% for 160 uM nickel acetate, 28.32% for 320 uM nickel acetate, and 45.21% for 480 uM nickel acetate.

Nickel-treatment significantly reduced levels of Bcl-2 and Bcl-xL proteins (which regulate the mitochondrial apoptotic pathway). However, nickel-treatment increased levels of Bad, Bcl-Xs, and Bax proteins in a concentration-dependent manner.

Nickel-treatment resulted in a significant increase in cytosolic cytochrome c, but a decrease in mitochondrial cytochrome c (indicating a dose-dependent release of cytochrome c). This is typically associated with reduction of MMP (as reported above). Also caspases were significantly activated compared to control cells.

Applicant's summary and conclusion

Executive summary:

Study was rated by an independent reviewer.