Quinolone in vitro studies

[Guest guest]

Tony wrote:

I've taken megadoses of cipro and believe me everything went with

the drugs ability to kill or it's inability to kill. I could take a

cipro when it was resistant to my organisms and I didn't flicker.

Tony,

A couple of years ago I would have thought maybe you were correct on

this, except that healthy, normal people rupture tendons sometimes on

day 3 the first time they ever take Cipro. But since two years ago I

have come across more studies sent me by Barb Peck on what it seems

quinolones are actually doing to cause tendon rupture. It looks like

it is linked to reduced magnesium levels.

a - with thanks to Barb Peck

Arch Toxicol. 2000 Jan;73(10-11):557-63. Links

Ciprofloxacin causes cytoskeletal changes and detachment of human and

rat chondrocytes in vitro.

Egerbacher M,

Seiberl G,

Wolfesberger B,

Walter I.

IV Medizinische Abteilung mit Infektions- und Tropenkrankheiten,

Kaiser Franz f Spital, Kundratstrasse, 1100 Wien, Austria.

monika.egerbacher@...

Quinolones cause damage of articular cartilage in different species

by forming chelate complexes with divalent cations and inducing

magnesium deficiency. Cations are important for regular function of

integrins, a group of transmembrane proteins which connect

extracellular matrix proteins with the intracellular cytoskeleton. We

have shown that cultivation of rat chondrocytes in ciprofloxacin

(CFX)-supplemented and Mg(2+)-free medium led to pronounced changes

in the cytoskeleton and decreased adhesion of cells to the culture

dish. In order to test whether or not these effects are species-

specific, we extended our studies on human chondrocytes. Human

chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and

160 microg/ml) or Mg(2+)-free medium showed decreased ability to

adhere to growth support, cell shape changes, and alterations in

actin and vimentin cytoskeleton in a concentration dependent manner.

Attachment of human chondrocytes to collagen type II coated cover

slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on

day 1. This effect even increased after 4 days of culture in the

respective medium (32% in CFX and 58% in Mg(2+)-free group). We

concluded that Mg(2+) deficiency is exerted via integrins, resulting

in decreased ability to attach to extracellular matrix proteins and

cytoskeletal changes. These effects are not species-specific. The

attachment assay proves to be an easy to use experimental set-up to

test ciprofloxacin and other quinolones for their chondrotoxic

effects.

Arch Toxicol. 2000 Jan;73(10-11):557-63. Links

Ciprofloxacin causes cytoskeletal changes and detachment of human and

rat chondrocytes in vitro.

Egerbacher M,

Seiberl G,

Wolfesberger B,

Walter I.

IV Medizinische Abteilung mit Infektions- und Tropenkrankheiten,

Kaiser Franz f Spital, Kundratstrasse, 1100 Wien, Austria.

monika.egerbacher@...

Quinolones cause damage of articular cartilage in different species

by forming chelate complexes with divalent cations and inducing

magnesium deficiency. Cations are important for regular function of

integrins, a group of transmembrane proteins which connect

extracellular matrix proteins with the intracellular cytoskeleton. We

have shown that cultivation of rat chondrocytes in ciprofloxacin

(CFX)-supplemented and Mg(2+)-free medium led to pronounced changes

in the cytoskeleton and decreased adhesion of cells to the culture

dish. In order to test whether or not these effects are species-

specific, we extended our studies on human chondrocytes. Human

chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and

160 microg/ml) or Mg(2+)-free medium showed decreased ability to

adhere to growth support, cell shape changes, and alterations in

actin and vimentin cytoskeleton in a concentration dependent manner.

Attachment of human chondrocytes to collagen type II coated cover

slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on

day 1.

This effect even increased after 4 days of culture in the respective

medium (32% in CFX and 58% in Mg(2+)-free group). We concluded that Mg

(2+) deficiency is exerted via integrins, resulting in decreased

ability to attach to extracellular matrix proteins and cytoskeletal

changes. These effects are not species-specific. The attachment assay

proves to be an easy to use experimental set-up to test ciprofloxacin

and other quinolones for their chondrotoxic effects.

1: Vet Pathol. 2001 Mar;38(2):143-8. Links

In vitro evidence for effects of magnesium supplementation on

quinolone-treated horse and dog chondrocytes.

Egerbacher M,

Wolfesberger B,

Gabler C.

Institute of Histology and Embryology, University of Veterinary

Medicine, Vienna, Austria.

Quinolones and magnesium deficiency cause similar lesions in joint

cartilage of young animals. Chondrocytes cultivated in the presence

of quinolones and in Mg-free medium show severe alterations in

cytoskeleton and decreased ability to adhere to the culture dish. We

investigated whether Mg2+ supplementation can prevent quinolone-

mediated effects on chondrocytes in vitro. Chondrocytes cultivated in

Dulbecco's modified Eagle's medium/HAM's F-12 medium were treated

with ciprofloxacin (80 and 160 microg/ml) and enrofloxacin (100 and

150 microg/ml). Mg2+ was added at a concentration of 0.0612 mg/ml

(MgCl) and 0.0488 mg/ml (MgSO4) or a triple dose. In addition, cells

were cultivated in Mg-free medium and accordingly treated with Mg2+

supplementation. After 5 days in culture, the number of adherent

cells per milliliter was determined.

The number of chondrocytes in quinolone-treated groups decreased to

12-36% that of the control group within the culture period. With Mg2+

supplementation, the number of attached cells increased to 40-70%

that of control cells. The threefold dose of Mg2+ led to better

results than did the single dose. Cell proliferation tested by

immunohistochemical staining with Ki67 (clone MIB5) decreased from

70% in control groups to 55%, 48%, and 30% in enrofloxacin-treated

groups in a concentration dependent manner (50, 100, and 150

microg/ml). Addition of Mg2+ did not increase the rate of cell

proliferation.

These results suggest that a great part of quinolone-induced damage

is due to magnesium complex formation, as Mg2+ supplementation is

able to reduce the effects in vitro. However, quinolone effects on

cell proliferation seem to be an independent process that is not

influenced by magnesium supplementation.

PMID: 11280370 [PubMed - indexed for MEDLINE]