Morphological changes induced by cyclophosphamide in crypt epithelium of the small intestine in mice: Light and electron microscopic studies

Abstract

When a single sublethal dose (300 mglkg body weight) of cyclophosphamide was injected intraperitoneally into experimental mice, several morphological alterations were detected in the crypt epithelium within a few hours. These were (a) mitotic activity of epithelial cells decreased, reaching the lowest level a t 16 hours; (b) an abnormally high number of lymphocytes and cells with eosinophilic granules appeared in the epithelium; later these cells degenerated and the maximum number of dead cells was observed a t six hours after the drug injection. At four days post-injection the morphology of crypt epithelium had returned to normal.Electron microscopic examination revealed that although the mitotic activity of crypt epithelial cells was depressed, there was little change in their morphology following the drug administration. However, many intermediate stages of degeneration of lymphocytes and eosinophilic cells were observed in the intercellular spaces as well as apparently inside the cytoplasm of crypt epithelial cells. The eosinophilic cells are characterized by the presence of large crystal-containing granules in the cytoplasm, and are believed to be equivalent to "globular leucocytes" described by many investigators. Evidence from this study suggests that lymphocytes and globular leucocytes are more sensitive to cyclophosphamide than crypt epithelial cells, and that they degenerate in crypt epithelium.

Ultrastructure of Macrophages and Karyolytic Bodies in Small Intestinal Villi of Macaque Monkeys and Baboons

“…Senescent enterocytes are known to be extruded from the tips of villi before undergoing pyknosis or karyolysis [6,8,291. Karyolytic bodies are a characteristic finding in intestines subjected to irradiation [lo, 14,191 or treatment with antimitotic drugs [20,24,28,301, but are located in the crypts, not at the tips of villi. Their origin is controversial.…”

“…Their origin is controversial. Some believe they originate from lymphocytes or other leukocytes [24,301, others from enterocytes [20,281, and still others from both [lo, 141.…”

Effects of the Aqueous Extract of Epimedii Herba on the Induction of Oral Tolerance in Mice.

“…Nevertheless, the use of CP as a modulator of the oral tolerance in vivo has a disadvantage since CP is a potent pharmacological agent with a wide range of actions, including a potential for damaging the intestine. 17) Therefore, it would be important to modulate an animal model of oral tolerance using agents with a more physiological action, with little or no adverse side-effects to promote immune responses via enhanced Th cell functions in inhibitory modulation.…”