Magnesium

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Materials and methods well described; results presented properly in the text and tables.

Data source

Reference

Reference Type:

publication

Title:

Effects of long-term dietary intake of magnesium on rat liver transcriptome.

Author:

Martin H, Staedtler F, Lamboley C, Adrian M, Schumacher MM, Chibout SD, Laurant P, Richert L, Berthelot A.

Year:

2007

Bibliographic source:

Magnes Res. 2007 Dec;20(4):259-65.

Materials and methods

Type of study / information:

InvestigatIon the effect of a two-year treatment period with a diet containing 3.2g, 0.8 g and 0.15 g Mg/kg, on the rat liver transcriptome.

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

mRNA expression in rat liver

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium oxide

EC Number:

215-171-9

EC Name:

Magnesium oxide

Cas Number:

1309-48-4

IUPAC Name:

magnesium oxide

Test material form:

solid: compact

Details on test material:

- Name of test material (as cited in study report): magnesium oxide

Results and discussion

Any other information on results incl. tables

The present work gives further evidence that the Mg content in the diet has pleiotropic effects on liver and impacts different pathways including metabolism, cytoarchitecture (connective tissue/cell adhesion/cytoskeleton), channels/transporters, turn-over (nucleic acid and protein), and homeostasis (stress/DNA damage/apoptosis/ageing). Taken together, these results suggest that a chronic low Mg dietary intake participates in an acceleration of ageing and liver dysfunction, thus having a strong impact on human health recommendations.

A treatment dependent decrease in plasmatic magnesium concentration was found. 0.86 +/- 0.02 mmol/L, 0.70 +/- 0.02 mmol/L and 05.2 +/- 0.03 mmol/L for groups receiving 3.2 g, 0.8 g and 0.15 g Mg/kg diet, respectively. No significant treatment-related effect on body and liver weights were observed. Magnesium dose-dependently increased the mortality rate. Magnesium content in diet affected gene expression in rat livers, as assessed by rat specific DNA microassays.

Applicant's summary and conclusion

Conclusions:

The present work gives further evidence that the Mg content in the diet has pleiotropic effects on liver and impacts different pathways including metabolism, cytoarchitecture (connective tissue/cell adhesion/cytoskeleton), channels/transporters, turn-over (nucleic acid and protein), and homeostasis (stress/DNA damage/apoptosis/ageing). Taken together, these results suggest that a chronic low Mg dietary intake participates in an acceleration of ageing and liver dysfunction, thus having a strong impact on human health recommendations.
A treatment dependent decrease in plasmatic magnesium concentration was found. 0.86 +/- 0.02 mmol/L, 0.70 +/- 0.02 mmol/L and 05.2 +/- 0.03 mmol/L for groups receiving 3.2 g, 0.8 g and 0.15 g Mg/kg diet, respectively.
No significant treatment-related effect on body and liver weights were observed.
Magnesium dose-dependently increased the mortality rate.
Magnesium content in diet affected gene expression in rat livers, as assessed by rat specific DNA microassays.

Executive summary:

In the present study the autors investigated the effect of a two-year treatment period with a diet containing 3.2g, 0.8 g and 0.15 g Mg/kg, on the rat liver transcriptome. At the end of the study, a treatment-dependent decrease in plasmatic Mg concentration was found (0.86 +/- 0.02 mmol/L, 0.70 +/- 0.02 mmol/L and 0.52 +/- 0.03 mmol/L for groups receiving 3.2g, 0.8 g and 0.15 g Mg/kg diet, respectively). No significant treatment-related effect on body and liver weights was observed, however a dietary Mg intake-dependent increase in mortality rate occurred in animals (11%, 25% and 38% death of animals). Mg content in the diet affected gene expression in rat livers, as assessed by rat specific DNA microarrays. We identified 11 genes up-regulated and 39 genes down-regulated by at least two-fold by a decrease in Mg content and grouped them within five functional pathways: metabolism 20%, cytoarchitecture (connective tissue/cell adhesion/cytoskeleton) 12%, channels/ transporters 20%, turn-over (nucleic acid and protein) 16%, and homeostasis (stress/DNA damage/apoptosis/ageing) 32%. The results of the present study confirm the pleiotropic effects of Mg and provide further evidence that a Mg decrease in the diet may be considered as a promoting factor for pathologies, especially in the liver, during ageing.