Superoxide production by stimulated equine polymorphonuclear leukocytes‐inhibition by anti‐inflammatory drugs

Abstract

Polymorphonuclear leukocytes (PMNLs) were isolated from an inflammatory exudate induced in the intercarpal joints of horses by an administration of carrageenin. Their superoxide production at rest and following stimulation with either serum-treated zymosan (STZ) or phorbol myristate acetate (PMA) was measured by cytochrome-c reduction. Stimulation of the cells increased the cytochrome-c reduction 10-15 times that of resting cells. The maxima were 20 nmol of reduced cytochrome-c per 10(6) cells per ml at 120 min (STZ) and 35 nmol of reduced cytochrome-c per 10(6) cells per ml at 60 min (PMA). The maximum inhibition of the cytochrome-c reduction by superoxide dismutase (Palosein) was 83.6% (STZ stimulation) and 72.1% (PMA stimulation). The non-steroidal anti-inflammatory drugs, phenylbutazone, salicylic acid, aspirin, sodium salicylate in addition to D-penicillamine and dimethylsulfoxide caused dose-dependent inhibition of the cytochrome-c reduction when the cells were stimulated by PMA. The maximum inhibitions were 64% and 36% for aspirin (10(-2) M), 32% and 17% for phenylbutazone (10(-3) M), 15% and 31% for dimethylsulfoxide (6.4 x 10(-1) M), 32% and 19% for salicylic acid (10(-2) M), 0% and 17% for sodium salicylate (10(-2) M) and 2.2% and 2.5% for D-penicillamine (10(-4) M) when the cells were stimulated by STZ and PMA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vitro Evaluation of the Effect of Dimethyl Sulfoxide on Equine Articular Cartilage Matrix Metabolism

“…Free radicals have been reported in the synovial fluid of horses with synovial inflammation and are considered to play an important role in the pathogenesis of equine inflammatory joint disease 17,19 . DMSO causes a dose‐dependent inhibition of superoxide radicals produced by stimulated neutrophils, and, in theory, the clinical benefit of DMSO would include this free radical scavenging ability 12–14 . There are, however, no controlled clinical studies documenting the efficacy of DMSO in a septic arthritis model.…”

“…Despite the potential adverse effects of DMSO, it often has been used intraarticularly in horses because of antiinflammatory and free radical scavenging properties believed to be beneficial in the management of inflammatory joint disease 10–14 . For example, DMSO inhibited hydroxyl radical mediated depolymerization of hyaluronan and suppressed prostaglandin production by oxygen derived free radicals (ODFR) 1,3,12,13 . Topical application of a gel formulation of DMSO decreased mean synovial white blood cell concentration in an equine synovitis model 11 .…”

“…In a healthy joint environment, resident chondrocytes regulate the composition of the matrix, maintaining uniform physical properties. However, disturbances in joint equilibrium and the generation of inflammatory mediators such as ODFR can result in a loss of matrix components, ultimately progressing to irreversible cartilage damage 13,18,19 . Traumatic and inflammatory insults or intraarticular medications that upset articular cartilage homeostasis can initiate osteoarthritis.…”

Reacciones adversas de los fármacos en los equinos

“…La inhibición máxima (para la síntesis de adhesinas y la actividad fagocítica de los macrófagos, respectivamente) fue de 64% y 36% para el ácido acetilsalicílico; 32% y 17% para la fenilbutazona; 15% y 31% para el sulfóxido de dimetilo; 32% y 19% para el ácido salicílico y 0% y 17% para el salicilato de sodio. 157 Hay una gran variedad de RA debido a la distribución de enzimas capaces de formar eicosanoides y a sus muchas funciones fisiológicas, 158 los efectos colaterales más comunes de los AINE se asocian con el tubo gastrointestinal (TGI), el sistema hematopoyético y el renal. En raras ocasiones se observa meningitis aséptica, depresión del SNC o hepatotoxicidad.…”

“…159 El aumento en el tiempo de protrombina puede potencializar la epistaxis en algunos caballos en entrenamiento, durante o después del ejercicio. 158,159 Ácido meclofenámico…”