Comparison of the Antiinflammatory Activities of Copper Complexes in Different Models of Inflammation

Lewis, Alan J.; Smith, W. Ewen; Brown, D. H.

doi:10.1007/978-1-4612-5829-2_29

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…The relevance of these observations is that they indicate the existence, in the serum, of a source of pharmacologically-inactive copper from which the endogenous metal could be removed to be eventually converted into pharmacologically-active complexes. (4) With the exception of D-penicillamine whose capacity of lowering blood and tissue levels of copper has been proved in normal rats [56,57] and whose administration caused a decrease of serum copper in arthritic patients [24,71 ], the ability of all the other major antiinflammatory/anti-arthritic drugs to interfere with copper metabolism in inflammatory conditions is still largely questionable [6,24,26,71,72]. Moreover, with the possible exception of D-peniciUamine whose mechanism of action as an anti-arthritic agent may be a copperdependent one [73], the hypothesis of SORENSON, in which the copper coordination compounds that are thought to be formed in vivo are proposed to be responsible for the anti-inflammatory activity of the clinically used anti-inflammatory drugs [44], does not have sufficient experimental support.…”

Section: (B) Administration Of Ligands Selective For Coppermentioning

confidence: 99%

“…Percutaneous applications, which have a kind of precursor in the copper bracelet, could be effective especially if, beside copper, the ligand used possesses antiinflammatory properties [64,65]. The oral route of administration might be the first to be considered but, at least in the rat, very few copper complexes are effective after such oral dosing [6,8]. This is most likely due to their breakdown at the acidic pH present in the stomach [63], so consequently the copper ions released from the complex will undergo the highly efficient homeostatic control of organism that tends to prevent much of the metal from being assimilated [31,60].…”

Section: Possible Relevance To Therapy Of the Copper Approachmentioning

confidence: 99%

“…Comprehensive reviews have been published recently summarizing the biochemistry and the pharmacological activities of copper in the treatment of rheumatoid arthritis and other degenerative connective tissue diseases [5], and reporting the ability of copper complexes to reduce the symptoms of chronic inflammation, especially adjuvant arthritis, in laboratory animals [5][6][7][8]. On the other hand, pulverized metallic copper and simple copper salts, like basic copper acetate and copper(II) sulphate, were used 3500 years ago for treating chronic inflammation of the eye [9]; moreover, the copper bracelet, an old anti-arthritic remedy belonging to the popular tradition, has been recently evaluated on a scientific ground revealing to possess a potential therapeutic value which cannot be entirely neglected [10,11].…”

Section: Copper In Chronic Inflammation (A) Therapeutic Value Of Coppmentioning

confidence: 99%

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Review: Copper and inflammation — a possible rationale for the pharmalogical manipulation of inflammatory discorders

et al. 1985

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Acute and chronic inflammations are characterized, among other features, by changes in the metabolism of copper and by a widespread responsiveness to the therapy with copper-containing molecules. The exact map of inflammation-induced copper movements as well as the role played by the metal in the pathogenesis of inflammatory disorders are, however, far from being clear, and this is especially true in the case of chronic processes. Nevertheless the present knowledge suggests that the "copper approach' may provide a new way for coping with the problem of anti-inflammatory/anti-arthritic therapies. The administration of exogenous copper, and the in vivo manipulation of the endogenous metal levels are proposed as two possible therapeutic strategies, not necessarily mutually exclusive. For a better understanding of the value of such an approach, further research work is needed, especially to attain a more detailed know-how on the involved chemical forms, distribution and functions of copper in both normal as well as inflamed organisms.

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Section: (B) Administration Of Ligands Selective For Coppermentioning

confidence: 99%

Section: Possible Relevance To Therapy Of the Copper Approachmentioning

confidence: 99%

Section: Copper In Chronic Inflammation (A) Therapeutic Value Of Coppmentioning

confidence: 99%

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Review: Copper and inflammation — a possible rationale for the pharmalogical manipulation of inflammatory discorders

et al. 1985

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“…The value of copper administration in the treatment of rheumatic diseases has been suggested for more than 1000 years [1] and more recently confirmed by clinical studies showing that copper complexes possess antiinflammatory effects both in animals [2] and in man [3]. Dietary copper restriction in the rat significantly increases the acute inflammatory reaction [4] but apparently inhibits the development of complete adjuvant arthritis [5].…”

Section: Introductionmentioning

confidence: 99%

Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats

et al. 1988

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Trace elements such as zinc, copper and selenium are involved in the pathogenesis of inflammatory diseases. In order to obtain more information about the overall movements of these minerals during the evolution of an experimental chronic inflammatory process, trace element levels were determined in five body compartments of the rat at several time intervals after induction of adjuvant arthritis. Rapid and significant changes in plasma zinc and copper levels and in liver zinc levels were observed. These modifications occurred as early as those in biochemical parameters of inflammation such as serum fibrinogen and ceruloplasmin, and preceded the appearance of any clinical symptom of the disease. Inverse correlations were found between plasma zinc levels and these two biochemical indices. Other modifications in trace element levels were observed two weeks after disease induction, the most important being a considerable increase in liver copper levels. Although food intake of affected animals decreased with the progression of the disease, there was no evidence of depletion in zinc and copper levels over the study period. A redistribution of body zinc between different biological compartments (mainly plasma and liver) occurred simultaneously with an accumulation of copper in several organs. The decreasing selenium status of animals was not clearly related to the inflammatory process.

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“…Although the drugs were applied at relatively high dose rates (31-37 mgCu/kg, ligand 350-385 mg/kg), there was no apparent local or systemic toxicity. However, copper complexes are generally applied to the skin because other routes of administration are often unsuitable as irritancy (subcutaneous), inactivity (oral) and toxicity (parenteral) are encountered (Lewis et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Copper salicylate and copper phenylbutazone as topically applied anti‐inflammatory agents in the rat and horse

Auer

Seawright

1990

Vet Pharm & Therapeutics

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Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as anti-inflammatory agents in rats and horses. Dimethylsulfoxide and glycerol (80:20) or dimethylsulfoxide, ethanol and glycerol (60:20:20) were used as the drug solvents. Subcutaneously administered carrageenin was used to induce inflammatory oedema, either in the paws of rats or the alar fold of the horse. The severity of the oedema and the anti-inflammatory effect of the drugs were assessed by measuring changes in the paw or alar-fold diameters. Copper salicylate and copper phenylbutazone were effective inhibitors of the inflammatory oedema in both species, but dimethylsulfoxide:glycerol (80:20) was not. In the rat, copper salicylate and copper phenylbutazone were superior anti-inflammatory agents compared to either salicylate or phenylbutazone, respectively. Following the topical application of four times the recommended daily dose of copper phenylbutazone to the horse for 5 days, minor skin irritation occurred and trace concentrations of phenylbutazone (maximum 0.6 microgram/ml) and negligible concentrations of oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in the plasma.

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Comparison of the Antiinflammatory Activities of Copper Complexes in Different Models of Inflammation

Cited by 7 publications

References 18 publications

Review: Copper and inflammation — a possible rationale for the pharmalogical manipulation of inflammatory discorders

Review: Copper and inflammation — a possible rationale for the pharmalogical manipulation of inflammatory discorders

Changes in zinc, copper and selenium status during adjuvant-induced arthritis in rats

Copper salicylate and copper phenylbutazone as topically applied anti‐inflammatory agents in the rat and horse

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