Effects of steroidal and non-steroidal antiphlogistic drugs on eicosanoid synthesis in irritated skin: studies with the isolated perfused bovine udder

Abstract

Using the isolated perfused bovine udder as an in-vitro model of skin inflammation, the effects of topically administered arachidonic acid on prostaglandin and leukotriene synthesis have been shown previously. In this study, the effects of indometacin (indomethacin) and clobetasol-17-propionate (administered topically) as well as flunixin meglumine and meloxicam (administered via the perfusion fluid) have been studied. Compared with controls, arachidonic acid caused a significant increase in the dermal prostaglandin E2 (PGE2) and peptidoleukotriene (LTC4/D4/E4) concentration. Topical treatment with indometacin (1.6 mg cm(-2)) and clobetasol-17-propionate (90 microg cm(-2)), which were administered 60 min before arachidonic acid administration, inhibited the inflammatory reaction. Flunixin meglumine (1 microg mL(-1) perfusion fluid) was administered 30 min after and meloxicam (3 microg mL(-1) perfusion fluid) was administered 60 min before arachidonic acid application. Three hours after arachidonic acid administration, a significant inhibition of PGE2 synthesis was induced by flunixin. In contrast, meloxicam showed only a slight effect. The effect of flunixin was comparable with in-vivo results. It is known from animal studies that anti-inflammatory effects of meloxicam are obvious within up to 6 h after treatment. Therefore, the incomplete effect of meloxicam may be explained pharmacokinetically. In conclusion, the described in-vitro model seems to be suitable for studies of pharmacological effects on eicosanoid synthesis in the skin.

The release and vascular action of bradykinin in the isolated perfused bovine udder

“…Steps were therefore taken to minimise this (immediate flushing with well‐gassed Tyrode solution in the abattoir; minimal delay in setting up) and vascular endothelial function was also confirmed in the laboratory. The isolated, perfused udder preparation has been used to study mammary metabolism (Wood et al 1965; Hardwick, 1966), the mechanisms of milk production (Hardwick & Linzell, 1960) and the pharmacology (Kietzmann et al 1993) and pathophysiology (Bäumer & Kietzmann, 2001) of the skin. The present study shows that the isolated perfused udder is also a useful model for the study of local mediator release and modulation of mammary blood flow.…”

“…More recently, the isolated bovine udder perfused with Tyrode solution has been used in a series of studies by Kietzmann and his colleagues (e.g. Kietzmann et al 1993; Bäumer & Kietzmann, 2001) as an elegant model to study the cutaneous absorption of topical drugs. The model of Kietzmann and his colleagues was used as a starting point for the model described in the present paper.…”

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

“…The collection of different parameters (glucose consumption, lactate production, lactate dehydrogenase activity, and pH in the perfusate, histological examination) indicated that skin viability was retained during a six hour perfusion interval and determination of udder skin-fold thickness demonstrated that no edema developed (Kietzmann et al, 1993). Subsequently, different anti-inflammatory drugs, administered systemically via the perfusate or topically to the skin, were tested in the model for their effect on eicosanoid synthesis (Bäumer and Kietzmann, 2001). The perfusion model also served as the basis for studies on the transdermal absorption potential of vitamin E acetate from cosmetic formulations (Lampen et al, 2003).…”

SHORT-COMMUNICATION Evaluation of perfused bovine udder for gene expression studies in dairy cows

“…The validation of new methods is of great interest. One of these new methods, the isolated perfused bovine udder approach, has been used in studies of mammary gland metabolism (Massart-Leën et al, 1986;Ehinger et al, 2006) and cutaneous absorption of drugs and cosmetics (Bäumer and Kietzmann, 2001). Despite of its potential, the method has not been widely used to evaluate the response against pathogens.…”