Morphological Evaluation of Oxatomide – a New Anti-Allergic Drug in Guinea Pig Anaphylaxis

Abstract

The effects of oxatomide, a new anti-allergic drug, in protecting guinea pigs from acute anaphylactic shock have been evaluated by studying the morphologic changes in the lung with special focus on the topographical relationship between bronchiolar smooth muscle and peribronchiolar mast cells, during the anaphylactic reaction. After ovalbumin challenge of passively sensitized guinea pigs, the mast cells in the peribronchiolar area present the following characterstic alterations: general shape changes with the formation of multiple cytoplasmic pseudopods, a variable decrease in the number of granules, mitochondrial swelling and, most peculiarly, a consistent appearance of intranuclear microtubules. Cations, being localized with an oxalate-pyroantimonate precipitation technique, are displaced from the nuclei and the cytoplasm of mast cells that are presumed to be causally involved in the anaphylactic phenomenon. Guinea pigs, which have been orally treated with 2.5 mg/kg oxatomide before ovalbumin challenge show, together with a suppression of the anaphylactic symptoms, an almost total lack of the characterstic nuclear and mitochondrial changes in the peribronchiolar mast cells. These observations strongly suggest that at least part of the drug’s protecting effect can be attributed to its inhibiting action on mediator release from mast cells. The possible connection that might exist between mediator release, intracellular cation distribution and the appearance of intranuclear microtubules is discussed.