The Influence of Ascorbic Acid on Histamine Metabolism in Guinea‐pigs

Abstract

The influence of ascorbic acid on anaphylaxis has always been a subject of controversy. For example, Cohen (1939) and van Niekerk (1937) found that ascorbic acid did not protect guinea-pigs from anaphylactic shock, whereas Hochwald (1935) obtained protection with large doses. Further, Giroud, Giroud, Ratsimamanga & Rabinowicz (1936) found that, by using daily doses of ascorbic acid during the period of antibody formation, the degree of sensitization was increased, whilst Zolog (1924) claimed that it was reduced. The present study was designed to re-examine the action of ascorbic acid in anaphylaxis in guinea-pigs and to determine its effect on histamine metabolism and sensitivity. It was also thought of interest to study its effect in anaphylaxis and on the anaphylactoid reaction in rats. METHODSHistamine excretion in guinea-pigs. Groups of twelve male guinea-pigs (body weight 400 to 600 g) were given an oral water load (5% of body weight) every 2 hr for 6 hr, and urine was collected in 2-hr samples over 8 hr. To study histamine formation, histidine in doses of 250, 500 or 1,000 mg/kg was either dissolved in the second water load or given intraperitoneally at the same time as the second water load. The urine was assayed directly for its histamine content using the isolated atropinized guinea-pig ileum preparation. The first 2-hr sample represented the basal urinary level of free histamine for each guinea-pig, and subsequent samples gave a measure of the rate of decarboxylation of histidine. The method is similar to that described by Waton (1963).Sensitivity to histamine aerosol. Groups of twelve male guinea-pigs (body weight 150 to 200 g) were used. Each animal was placed in a desiccator and was made to inhale an aerosol of histamine (1% w/v) which was sprayed into the chamber at a pressure of 10 lb/sq in. As soon as it showed the characteristic convulsive cough, it was removed from the chamber and allowed to breathe air. The time taken to produce the first convulsive cough was called the " collapse time " or " preconvulsion time " and this value was used as a measure of the sensitivity of the animal to the histamine aerosol.Histamine content. The histamine content of various tissues of guinea-pigs was determined by the method of Parratt & West (1957). Briefly, the tissues were extracted with 10% (w/v) trichloracetic acid (5 ml./g), the excess acid was removed by ether, and the solution was assayed on the atropinized guinea-pig ileum for its histamine content.Formation ofhistamine in vitro. The method of Waton (1956) was used to study the rate of decarboxylation of histidine in tissues of guinea-pigs.Bronchoconstriction in vivo. Guinea-pigs were anaesthetized with chloralose (110 mg/kg, intraperitoneally) and then artificially ventilated with a constant volume pump through a tracheal cannula. Pressure in the trachea was recordea using a transducer system and drugs were injected into the jugular vein.

Actions of Sodium Ascorbate on Smooth Muscle

“…Rosa & Parenti (1950) used the vitamin in bronchial asthma and urticaria with some success, but Naranjo (1952) and Herxheimer (1955) obtained no protection against anaphylaxis in experimental animals. Hochwald (1935), van Niekerk (1937), Aron (1948) and Dawson & West (1965a) all showed a shortterm protective action of ascorbic acid against anaphylaxis in guinea-pigs. These protective effects have usually been obtained in guinea-pig and man in allergic conditions where contraction of the bronchial smooth muscle is of prime importance and it is suggested that the protection is due to a direct action of the vitamin on the smooth muscle.…”

“…Ascorbic acid may have a synergistic effect when administered with antihistamines against allergic phenomena (Dawson & West, 1965a) …”

EFFECT OF VARIATION IN ENDOGENOUS LEVELS OF ASCORBIC ACID ON THE in vitro IMMUNOLOGICAL RELEASE OF HISTAMINE AND SLOW REACTING SUBSTANCE OF ANAPHYLAXIS FROM ACTIVELY SENSITIZED GUINEA‐PIG LUNG FRAGMENTS

“…High doses of ascorbic acid protect sensitized guinea-pigs maintained on a normal diet against the effects of antigen aerosols ' (Dawson & West, 1965a;Guirgis, 1965). Actively sensitized scorbutic guinea-pigs are less sensitive to antigen aerosols than guinea-pigs maintained on normal diets (Dawson & West, 1965a).…”

Antioxidant-Vitamin C: Lung Function; Lung Cancer

“…The role of ascorbic acid (vitamin C) in asthma has long been argued, early as 1803 Reisseissen suggested that vitamin C prevents the wheezing observed in patients with diseases scurvy [4]. More recently, animal studies have shown that ascorbic acid may prevent anaphylaxis and other allergic phenomena [5,6]. In guinea pigs, ascorbic acid has been shown to reduce the airway obstruction prompted by 5-hydroxytryptamine, bradykinin, and histamine [7].…”