Effects of Solanum glaucophyllum toxicity on cell proliferation and apoptosis in the small and large intestine of rabbits

Abstract

Vitamin D regulates mineral homeostases and enterocyte proliferation and differentiation. Hypervitaminosis D generates changes in cell proliferation, differentiation and apoptosis in several organs. We analysed morphometric parameters and proliferative and apoptotic indices in the intestinal epithelium of rabbits with hypervitaminosis D induced by the chronic treatment with the calcinogenic plant Solanum glaucophyllum. Rabbits were treated for 15 or 30 days. A group was treated for 15 days and led to possible recovery for 30 days. Another group was nutritionally restricted for 30 days. Morphological, morphometric, proliferative and apoptotic changes were found in the treated animals. Mild atrophy and reduced proliferation was found in the jejunum and ileum. Apoptosis increased in the crypts of the ileum and in the superficial epithelium and crypts of the rectum. Most of the alterations were partially recovered. The possible involvement in these changes of the hypervitaminosis D-like state induced by S. glaucophyllum is discussed.

Fig. 1

Body weight variations in S. glaucophyllum-treated animals. Note the progressive reduction of body weight index with time in treated animals. All the groups showed a significant reduction in their body weight index in comparison to control group (p < 0.05).

Fig. 2

Morphological changes of the intestine. A–C: jejunum; D–F: ileum; G–I: rectum. A, D and G: control group. B, E: group B. H: group A. C, F and I: group C. Samples of jejunum and ileum of treated animals show atrophy of the villi. A mild recovery is observed in the same intestinal tracts in group C. Multifocal slight atrophy was observed in the rectum. All sections were stained with H–E. Bar = 1 mm.

Fig. 3

Pathological features of the intestine. All images belong to group B. Lymphangiectasia is observed in both jejunum (A) and ileum (B) (arrows). (C) oedema in the lamina propria (^∗) of the rectum. All sections were stained with H–E. Bar = 50 μm.

Fig. 4

Morphometric study of crypts and villi. Significant differences (^∗) in villi length of jejunum were observed (group A vs. control and group D) or villi width (#) (group C vs. control). Significant differences in crypt width (#) were observed (group C vs. all groups except group D). Significant differences (^∗) in villi length of ileum were observed (group A vs. control and group D) or villi width (#) (group C vs. group A). Significant differences in crypt length of rectum (^∗) were observed (group A vs. controls). The figure shows the means of the experimental groups and the 99% confidence interval on the treatment means. ^∗, # = p < 0.01.

Fig. 5

Ki-67 proliferation index in the intestine. The proliferation index was reduced in some S. glaucophylum-treated animals. In the jejunum, significant differences (^∗) were observed between group B vs. control and D groups. In the ileum, significant differences (#) were observed between group A and the rest of the groups. In the rectum significant differences (&) were observed between group D vs. group B. The figure shows the means of the experimental groups and the 99% confidence interval on the treatment means. ^∗, #, & = p < 0.01.

Fig. 6

Apoptosis of epithelial cells. In ileum crypts (^∗) significant differences vs. the remaining groups were observed. In the superficial epithelial cells and crypts of the rectum (^∗) significant differences vs. groups C and D were found. The figure shows the means of the experimental groups and the 99% confidence interval on the treatment means. ^∗ = p < 0.01.