Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery

Abstract

1 We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately 7, 7,3', 5,7,3', upon the permeability of single perfused capillaries and venules in the mesenteries of pithed frogs.2 In each experiment, the hydraulic permeability (Lp) of a single perfused microvessel and the effective osmotic pressure (aAic) exerted by macromolecules across its walls were estimated by a microcclusion technique, first during control perfusion and then in the presence of a known concentration of test substance.3 HR, M and 7,4'-di-HR reduced Lp in a similar concentration-dependent manner over the range of 1 tLg ml-' to 1 mg ml-' (maximum reduction was to 40% of control Lp at 1 mg ml-'). At perfusate concentrations greater than 1 mg ml-', these substances reduced Lp to a lesser extent. While the four other test substances reduced Lp significantly when their perfusate concentrations equalled or exceeded 100 ig ml-1, they were all less potent than 7,4'-di-HR. 4 The reduction in Lp induced by the mixture of flavonoids was only slightly reversed by subsequent perfusion with flavonoid-free solutions. 5 When permeability was increased by perfusing with protein-free solutions, both HR and 7,4'-di-HR reduced and then reversed the increase in Lp in a concentration-dependent manner over the range of 1 jg ml' to 100 yg ml-'. None of the other component flavonoids was effective in restoring Lp under these conditions.

Protective action of hydroxyethyl rutosides on singlet oxygen challenged cardiomyocytes

“…The recommended oral dose of 500 mg daily has proven to be effective in reducing oedema in post-thrombotic syndrome (Diebschlag et al, 1994). In experimental studies HR reduced microvascular permeability at concentrations equal or greater than 10 Mg ml-' (Kendall et al, 1993). In view of these data it appears reasonable to assume that the concentrations used in the present investigation may be relevant to the clinical situation.…”

“…However, incubation with HR covering the whole concentration range in the absence of rose bengal had no negative effect on the cardiomyocytes, leaving this possibility unlikely. A bell-shaped dose-response curve for HR has also been described recently in experimental studies on the permeability of microvessels in the frog mesentery (Kendall et al, 1993), as well as in clinical trials in patients with chronic venous insufficiency (Diebschlag et al, 1994). Flavonols have been shown to bind to biomembranes (Sorata et al, 1984) especially to membrane proteins (Gryglewski et al, 1987) which may result in the prevention of destabilization of cellular membranes.…”

“…Flavonols have been shown to bind to biomembranes (Sorata et al, 1984) especially to membrane proteins (Gryglewski et al, 1987) which may result in the prevention of destabilization of cellular membranes. To explain the bell-shaped dose-response relationship Kendall et al (1993) offered the hypothesis that HR bind at two different sites which give rise to opposite effects. According to Young et al (1992) a bell-shaped dose-response curve indicates the involvement of separate binding sites exerting non-competitive antagonism.…”

Intravenous Hydroxyethylrutosides Combined with Long-Term Oral Anticoagulation in Atherosclerotic Nonreconstructable Critical Leg Ischemia: A Retrospective Study

“…HR has been shown to inhibit red cell aggregation 8,9 to be a powerful antioxidant with free radical scavenging properties, 10,11 and to have endothelial cell protective, eg, antiedematous, effects 12 by inhibiting the permeability of the endothelial cell barrier. 13,14 It has also been shown to have affinity to, and become accumulated in, the endothelial cells of the vascular wall. 15 These properties have been summarized in a review Preliminary observations on very favorable effects of IV HR without anticoagulation in four of seven patients with &dquo;end-point&dquo; lower limb ischemia were reported in 1974 by Milliken.17 We report our study on the use of short-term intravenous HR and long-term anticoagulation (AC) with warfarin.…”

Effects of hydroxyethylrutosides on hypoxia‐induced activation of human endothelial cells in vitro

“…Hydroxyethylrutosides (HR) is a standardized mixture of semisynthetic flavonoids which has been shown to improve lower limb venous insufficiency in double-blind studies performed with objective and subjective criteria (Balmer & Limoni, 1980;Pulvertaft, 1983;Neumann & van den Broek, 1990). HR are known to reduce the capillary filtration rate in patients with venous insufficiency (Roztocil et al, 1977;Cesarone et al, 1992), to decrease microvascular permeability in several experimental models (Gerdin & Svensjo, 1983;Kendall et al, 1993) and to reduce oedema formation (Rehn et al, 1991). All these effects may explain the beneficial effect of HR in patients with venous insufficiency.…”