Effect of disodium cromoglycate on cutaneous basophil anaphylaxis

Cutaneous basophil anaphylaxis (CBA) was elicited by intradermal rechallenge of cutaneous basophil hypersensitivity (CBH) sites in guinea pigs sensitized 7 days previously with keyhole limpet hemocyanin (KLH). The antiallergy agent disodium cromoglycate (DSCG), administered i.v. immediately before rechallenge, inhibited the increased vasopermeability (measured by tissue dye uptake) and basophil degranulation (measured by light microscopic counts of intact basophils) characteristic of the CBA reaction. The antihistamine mepyramine, administered orally, inhibited vasopermeability but not basophil degranulation. The component contributed by DSCG inhibition of mast cell degranulation to the overall inhibition of the reaction was found to be minimal, since intact mast cells were found to be depleted at CBH sites and totally absent at CBA sites from animals treated with DSCG. Electron microscopic examination of basophils at CBA sites from DSCG-treated animals revealed the presence of ruffled perigranular membranes and enlarged perigranular spaces, but both the formation of degranulation sacs and the subsequent fusion of granule sac membranes with the plasma membrane were inhibited. DSCG also inhibited the vasopermeability and basophil degranulation of the CBA reaction elicited by KLH at day 14 and by C5a at day 7. When a basophil-enriched leucocyte preparation from KLH-sensitized guinea pigs was studied in vitro, DSCG inhibited both antigen-induced and C5a-induced basophil degranulation at 10(-5) and 10(-4) M. DSCG failed to inhibit the vasopermeability and the mast cell degranulation produced by either intradermal C5a or intradermal compound 48/80. These results indicate that anaphylactic degranulation of basophils, but not mast cells, is inhibited by DSCG in the guinea pig. This inhibition appears to take place independent of stimulus at an early stage of granule membrane fusion.     

Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions

We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction.     

Reaction of disodium cromoglycate with hydrated electrons

A possible mechanism by which disodium cromoglycate (DSCG) prevents a decrease in regional cerebral blood flow but not hypotension in primates following whole body gamma-irradiation was studied. Several studies have implicated superoxide radicals (O2-.) in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively. O2-. is formed during radiolysis in the reaction between hydrated electrons (e-aq) and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge e-q and possibly prevent the formation of O2-. was studied. Hydrated electrons were produced by photolysis of potassium ferrocyanide solutions. The rate constant, k = 2.92 x 10(10) M-1s-1 for the reaction between e-aq and DSCG was determined in competition experiments using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). This spin trap reacts rapidly with e-aq followed by protonation to yield the ESR observable DMPO-H spin adduct. The results show that DSCG is an efficient e-aq scavenger and may effectively compete with oxygen for e-aq preventing the radiolytic formation of O2-..