Protection of mouse jejunum against lethal irradiation by Podophyllum hexandrum

Radiation induced gastrointestinal damage occurs due to the destruction of the clonogenic crypt cells and eventual depopulation and denudation of the villi. P. hexandrum, a plant, known for its antitumour activity, has been shown to protect the mice against whole body lethal (10 Gy) irradiation. Present study was undertaken to investigate the radioprotective effect of P. hexandrum on jejunal villi cells, crypt cells, their proliferative capacity and mitigation of apoptosis.

In an in vivo micro colony survival assay, pre-irradiation administration of P. hexandrum (–2 h) increased the number of surviving crypts in the jejunum by a factor of 3.0 (P < 0.05) and villi cellularity by 2.7 (P < 0.05) fold in comparison to irradiated control. Pre-irradiation administration of P. hexandrum reduced the incidence of apoptotic bodies in the crypts (P < 0.05) in a time dependent manner and depicted a mitotic arrest till the 24 h. However, after 84 h the percentage of mitosis was observed to be nearly similar to that of unirradiated control.

This study suggests that arrest of cell division may help in protecting the clonogenic cells against radiation. It would be interesting to investigate further the role of P. hexandrum in influencing various cell cycle regulators like bcl-2, TGF-β, Cyclin-E etc.     

The distribution of endocrine cells along the mouse intestine: A quantitative immunocytochemical study

The topographical distribution of endocrine cells in the crypt and villus epithelium along the length of the mouse intestine was studied. Argyrophil reactivity using the Grimelius stain was used to estimate the total endocrine population of the intestine. Comparisons were then made with the fraction of endocrine cells containing glucagon like material, stained immunocytochemically using rabbit anti-glucagon antisera. A highly significant reduction in the incidence of endocrine cells (argyrophil reactive) from the proximal to distal end of the intestine was noted. However, only 10-30% of these cells contained glucagon like material in the crypts of the duodenum, jejunum and ileum, compared to 30–60% in the crypts of the colon and rectum. The distribution of endocrine cells (argyrophil reactive) was maximal in the lower regions of the proliferative zone of the crypts but showed no significant variation along the length of the villi. Cells containing glucagon like material were also most frequent in the lower regions of the proliferative zone of the crypts, but were not generally found above the botom third of the villi. Each crypt in the small intestine contains between 3 and 5 endocrine cells one of which contained glucagon like immunoreactive material. In the colon and rectum each crypt contains about 6-8 endocrine cells, of which 3–4 contained glucagon like immunoreactive material. These results indicate that a sub-set of cells containing glucagon like material, differentiate early in the lineage of endocrine cells within the proliferative zone of the intestinal crypts.     

Daily Variations in Colchicine‐Induced Apoptosis in Duodenal Crypts

Apoptotic cell death can be induced by several agents, among them colchicine, a microtubule disrupting‐drug that affects continuously renewing cell populations, such as the intestinal crypt enterocytes. The objectives of this investigation were (1) to confirm in vivo colchicines‐inductive effect and (2) to determine the existence of 24 h variations in the crypt enterocytes apoptotic indices. The study was done on C3H/S male adult mice housed under standardized conditions. Starting at midnight until the end of a circadian period, subgroups of mice were sacrificed after having been injected with colchicine or saline i.p. 4 h beforehand. Duodenal samples were processed for hematoxylin‐eosin staining and TUNEL technique. In order to score the number of apoptosis, the longitudinal sections of the crypts were divided into three regions comprised, respectively, of tiers 1–4, 5–12, and 13–20, proceeding from the bottom to the top of the crypt. Values of each lot were expressed as mean±SEM. A highly significant statistical difference in apoptotic indices was found for colchicine‐treated animals. The 24 h curve for colchicine‐induced apoptosis displayed qualitative and quantitative differences compared to other inducer agents. Highest apoptotic indices were found in the deepest crypt regions. Daily variations were observed in all the crypt sectors of the colchicine‐treated animals and in tiers 5–12 of the saline controls. The present work demonstrates that the colchicine cytotoxicity due to its apoptotic‐inducing effect depends on the dosing time during the 24 h in this mouse strain.     

Kinins induce rapid structural changes in colon concomitant with chloride secretion

Summary Voltage-clamped colonic epithelia were fixed for morphological observation minutes after bradykinin was added to produce its well-characterized increase in short circuit current representing net chloride secretion. With respect to paired controls, the average distance from the luminal epithelial surface to the underlying muscularis mucosa decreased significantly with time, and was accompanied by marked structural alterations in the crypts of Lieberkühn and surrounding lamina propria. This rapid reconfiguration of epithelial architecture suggests that kinin-receptor interaction leads to epithelial contractile events which occur simultaneously with net chloride secretion.