Nutritional supplementation with copper in the rat. I. Effects on adjuvant arthritis development and on some in vivo- and ex vivo-markers of blood neutrophils.
OBJECTIVE
The aims of the work were: 1) to confirm the preliminarily observed anti-arthritic potential of a 200 ppm copper-supplemented diet in the rat: 2) to study the impact of the nutritional treatment and of the experimental pathology on neutrophil activity. ANIMALS AND CELLS: Two hundred female Sprague-Dawley rats were used. Polymorphonuclear leukocytes were isolated from these animals for the ex vivo studies.


METHODS
Control-rats were maintained on a standard diet containing 5 ppm of copper. Supplemented-rats were kept on a diet containing 200 ppm of the metal.


METHODS
Mycobacterium butyricum-induced arthritis was studied. Flame atomic absorption spectroscopy was used to assess copper and zinc levels. The "microplate-assay" technique was used to determine serum lysozyme concentration (lysis of Micrococcus lysodeikticus cell walls), as well as neutrophil O2- generation (superoxide dismutase-inhibitable reduction of ferricytochrome-c), and adhesion (activity of the membrane enzyme acid phosphatase). The results were statistically evaluated by the Student's t test.


RESULTS
The nutritional copper-supplementation: 1) significantly inhibited the adjuvant-arthritis development (33% +/- 5, P<0.01); 2) did not modify lysozyme secretion or superoxide production; 3) significantly decreased the percentage of cell adhesion by an average of 41% +/- 19 (P<0.01).


CONCLUSIONS
The copper-supplemented diet has an anti-arthritic effect which may be also primed by the effect of copper on the expression of the neutrophil cell-adhesion molecules.
Milanino
R
R
Istituto di Farmacologia, Facoltà di Medicina e Chirurgia, Università di Verona, Policlinico di Borgo Roma, Verona, Italy. milanino@farma.univr.it
Marrella
M
M
Crivellente
F
F
Benoni
G
G
Cuzzolin
L
L
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers; D001772:Blood Cell Count; D002448:Cell Adhesion / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D019587:Dietary Supplements; D004798:Enzymes / Q000097:blood; D005260:Female; D007958:Leukocyte Count; D009504:Neutrophils / Q000187:drug effects*; D009752:Nutritional Status; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000378:metabolism
D015415:Biomarkers; D004798:Enzymes; D003300:Copper; D015032:Zinc