On the Anti‐inflammatory Activity of Protamine Sulphate and of Hexadimethrine Bromide, Inhibitors of Plasma Kinin Formation

Kellett, D. N.

doi:10.1111/j.1476-5381.1965.tb01626.x

Cited by 19 publications

(17 citation statements)

References 20 publications

(8 reference statements)

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“…Specific antagonists of acetylcholine, histamine and 5-hydroxytryptamine such as atropine (200 mg/kg), mepyramine (50 mg/kg) and 2-bromolysergic acid diethylamide (10 mg/kg) respectively, as well as metabolic inhibitors of the dextran anaphylactoid reaction such as glucose (3 g/kg) or 2-deoxyglucose (500 mg/kg), had no effect on the thermic oedema. These results support the view that histamine and 5-hydroxytryptamine are not the chief mediators involved in the heat reaction at temperatures up to 46.50 C. -Hexadimethrine bromide, an anti-heparin agent, has been reported to be effective against yeast-induced rat paw oedema when used in doses of 20 mg/kg intraperitoneally (Kellett, 1965) but it was ineffective against thermic oedema. Similarly,-Trasylol (Bayer A.G., 5,000 kallikrein inactivator units/ml.)…”

Section: Inhibition Of Thermic Oedemasupporting

confidence: 81%

Bradykinin and Oedema Formation in Heated Paws of Rats

Starr

West

1967

British Journal of Pharmacology and Chemotherapy

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Histamine was considered to be the chief mediator in inflammatory reactions until it was shown that specific antihistamine drugs did not always inhibit-these reactions. The idea of the polypeptide nature of some of the unidentified permeability factors in inflammatory exudates was introduced by Menkin (1936). Armstrong, Jepson, Keele & Stewart (1957) noted the similarity of the actions of these factors with those of bradykinin, a nonapeptide. This compound or others related to it have since been found in many oedema fluids and were detected in the perfusates of rat paws after the application of heat (Rocha e Silva & Antonio, 1960).It was considered important to investigate in more detail the extent to which kinins participate in this so-called thermic oedema by following changes in four-kinin parameters in the perfusates. As rats which are resistant to the anaphylactoid reaction produced by dextran (the so-called non-reactors) also showed greater resistance-to thermic oedema than did the reactors giving the anaphylactoid reaction (Gecse, Karady, Starr & West, 1965), a comparison of the activity of the kinin systems in the perfusates collected from the heated paws of both types of rat was also made. In addition, a study of the effects of drugs on both the development of thermic oedema and the actions of bradykinin has been included. METHODSAdult Wistar albino rats were obtained from Fison's Ltd. (Holmes Chapel) and from the Agricultural Research Council's Field Station at Compton. They were tested for their reactivity to dextran (240 mg/kg, intraperitoneally) on three occasions, oedema developing in the extremities over a 2-hr period only in reactor rats (Harris & West, 1961). Both reactor and non-reactor rats were anaesthetized with pentobarbitone sodium (45 mg/kg, intraperitoneally) and their hind paws were perfused according to the method of Rocha e Silva & Antonio (1960). Before collecting the perfusates, the paw space was washed free of blood. The flow of perfusing fluid (Tyrode solution) was regulated to 5-10 drops/min, and then the paw was immersed in a water-bath maintained at the desired temperature for 30 min. Perfusates were collected for three consecutive periods of 10 min during the heating and for further periods after the heating. Samples were also collected from unheated paws to serve as controls.In other experiments, paws were heated without perfusion after the rats had been anaesthetized and given azovan blue dye intravenously (18 mg/kg, Bonaccorsi & West, 1963). The paws were then examined for the presence of oedema using the plethysmographic method of Buttle, D'Arcy,

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Section: Inhibition Of Thermic Oedemasupporting

confidence: 81%

Bradykinin and Oedema Formation in Heated Paws of Rats

Starr

West

1967

British Journal of Pharmacology and Chemotherapy

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“…The activation of the kinin system, either through the intervention of released histamine as suggested by Edery & Lewis (1963) or directly by the action of kininogens present in plasma and in the subcutaneous tissues would maintain the early vascular response (increased permeability to large molecules) to the point where the amount of extravasated proteins would be sufficient to induce the leakage of water through the vessel walls. In this respect, hexadimethrine bromide besides acting as an anti-inflammatory agent (Kellet, 1965;Garcia Leme et al, 1967) and having a marked inhibitory effect upon the activation of the kinin system (Armstrong & Stewart, 1962;Garcia Leme et al, 1970) proved in the present experiments to be a potent agent in counteracting the development of oedema and dye-leakage. It is to be noted that hexadimethrine bromide inhibits dye leakage even when given one hour after carrageenin.…”

Section: Discussionmentioning

confidence: 69%

Pharmacological analysis of the acute inflammatory process induced in the rat's paw by local injection of carrageenin and by heating

Leme¹,

Hamamura²,

Leite³

et al. 1973

British J Pharmacology

121

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Summary1. Local injection of carrageenin in the rat's paw produced oedema and leakage of dye which had been administered previously by the intravenous route. A net dissociation between both parameters was observed: while oedema developed slowly, maximal intensity being attained after 4-5 h, dye-leakage was maximum after 1 hour. 2. Anti-inflammatory drugs such as acetylsalicylic acid and indomethacin were effective in reducing oedema and dye-leakage when given before the injection of carrageenin, but much less effective when given 30 or 60 min after carrageenin. Hexadimethrine bromide was effective in reducing dye-leakage also when given 1 h after the injection of carrageenin. 3. Combined administration of benadryl and methysergide, before the injection of carrageenin caused only a slight reduction in oedema and dye-leakage.4. When the paws were heated (550 C for 30 s) as a noxious stimulus the dissociation between maximal oedema and maximal dye-leakage was not observed, both phenomena running parallel. Pre-treatment of the animals with indomethacin did not afford any protection. 5. These results suggest that the inflammatory reaction to mild stimuli (carrageenin in our experiments) develops through different phases: initially the increased vascular permeability involves extravasation of plasma proteins and that phase is followed by an increased permeability mainly to water. Stronger stimuli (heating in our experiments) produce an overlapping of both phases, probably by inflicting severe damage to the vascular bed of the affected area.6. The anti-inflammatory drugs employed affected chiefly the initial phase of the response. 1fitroductionDyes injected intravenously localize in areas of developing inflammatory reactions. Using xylene as an irritant applied to the skin of rabbits, Rigdon (1939Rigdon ( , 1940 was able to show that Trypan blue and Indian ink concentrate in the injured areas only when injected into the circulation immediately after or within a period of less than 3-5 h following the application of xylene, though after that time these skin areas exhibited all the macroscopic and microscopic alterations associated with the inflammatory response. Rigdon concluded that increased vascular permeability is of brief duration following injury where xylene is applied.

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“…[12,13] Briefly, the rats were fasted for 12 h before the experiment, but water was given ad libitum. Animals were pre-treated with vehicle and drugs orally 1 h before the experiment.…”

Section: Carrageenan-induced Paw Edema In Ratsmentioning

confidence: 99%

Preliminary phytochemical, toxicity and anti-inflammatory evaluation of Commelina benghalensis

Augustine¹,

Tiwari²,

Lahkar³

et al. 2013

Int J Green Pharm

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Background: Commelina benghalensis is a widely used ethno medicinal plant for various diseases in India, but only few studies have been conducted in this plant. Objective: The present work was performed to screen phytochemical, toxicity and anti-inflammatory activity of hydroethanolic extract of leaves of C. benghalensis (Family: Commelinaceae). Materials and Methods: Hydroethanolic extract of leaves of C. benghalensis (HECB) was prepared and subjected to preliminary phytochemical investigations. Acute and sub-acute toxicity tests were performed in female Wistar rats. The anti-inflammatory activity was studied using carrageenan-induced rat paw edema, cotton pellet granuloma and xylene-induced ear edema models at two different doses (200 mg/kg and 400 mg/kg of body weight). Results: HECB did not show any toxic reactions in female rats, and a dose of 400 mg/kg exhibited significant anti-inflammatory activity in all three models as compared to the control group. Indomethacin 10 mg/kg also showed significant anti-inflammatory activity in all three models. Conclusion: These experimental results have established a pharmacological evidence for the folkloric use of the C. benghalensis as an anti-inflammatory agent. Determination of the median lethal dose (LD 50 ) revealed that the Commelina extracts was safe.

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On the Anti‐inflammatory Activity of Protamine Sulphate and of Hexadimethrine Bromide, Inhibitors of Plasma Kinin Formation

Cited by 19 publications

References 20 publications

Bradykinin and Oedema Formation in Heated Paws of Rats

Bradykinin and Oedema Formation in Heated Paws of Rats

Pharmacological analysis of the acute inflammatory process induced in the rat's paw by local injection of carrageenin and by heating

Preliminary phytochemical, toxicity and anti-inflammatory evaluation of Commelina benghalensis

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