Effect of iron sucrose on human peritoneal mesothelial cells.
BACKGROUND
Iron supplementation is often required in uraemic patients with anaemia. Peritoneal cavity was proposed as an alternative intravenous route for iron infusion in patients treated with peritoneal dialysis. We studied the effect of iron sucrose (Venofer) on the function of human peritoneal mesothelial cells maintained in in vitro culture.


METHODS
In in vitro experiments on human peritoneal, the mesothelial effect of elemental iron (in conc. 0.0001-1 mg mL-1) present in Venofer on their viability, growth and synthesis of IL-6 was studied. Additionally we evaluated with a fluorescent probe (2',7'-dichlorodihydro-fluorescein diacatate) generation of reactive oxygen species in cells exposed to iron sucrose. We also measured accumulation of iron in the cytoplasm of mesothelial cells after their in vitro exposure to Venofer.


RESULTS
In in vitro conditions iron induces a dose-dependent inhibition of viability of the mesothelial cells as reflected by inhibition of the cells growth by 34% at Fe 0.1 mg mL-1 vs. control (P < 0.05) increased release of lactate dehydrogenase (LDH) from the cytosol: 67.1 +/- 30.3 mU mL-1 at Fe 1 mg mL-1 vs. 7.9 +/- 6.4 in control group (P < 0.001), and reduced synthesis of IL-6: 209 +/- 378 pg mg-1 cell protein at Fe 1 mg mL-1 vs. 38674 +/- 4146 pg mg-1 cell protein in controls (P < 0.001). Cytotoxicity of iron towards mesothelial cells was enhanced in vitro when it was tested in presence of the dialysis fluid. Iron used in vitro at concentration 0.0001 mg mL-1 and greater induces generation of oxygen-derived free radicals in mesothelial cells. Furthermore, iron is taken by these cells and stored in their cytosol, resulting in stimulation of the intracellular generation of free radicals.


CONCLUSIONS
We conclude that iron used in the form of iron sucrose is cytotoxic to human peritoneal mesothelial cells. Accumulation of iron sucrose within cytoplasm of these cells may lead to induction of its chronic cytotoxic effect.
Breborowicz
M
M
Poznań Medical School, Poznań, Poland, Institute of Kidney Lifescience Technologies, Toronto, Canada. abreb@am.poznan.pl
Polubinska
A
A
Tam
P
P
Wu
G
G
Breborowicz
A
A
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015314:Dialysis Solutions; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects*; D005290:Ferric Compounds / Q000494:pharmacology*; D000077605:Ferric Oxide, Saccharated; D005609:Free Radicals / Q000378:metabolism; D005937:Glucaric Acid; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D010529:Peritoneal Cavity / Q000166:cytology*
D015314:Dialysis Solutions; D005290:Ferric Compounds; D005609:Free Radicals; D015850:Interleukin-6; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid