The effects of bortezomib on the ovariectomy applied rat uterus: A histopathological, stereological, and immunohistochemical study

Abstract

Objectives: In this study, potential protective effects of Bortezomib (Bort), as a proteasome inhibitor, were investigated on the uterus of ovariectomized rats by histological, morphometric and immunohistochemical methods.

Materials and methods: In this study, 18 Sprague dawley strain female rats (12 weeks old, 250-300 g body weight) were used. Animals in the control group (Cont, n=6) were not exposed to any treatment. Ovariectomy was performed on the experimental groups. They (n=12) were divided into ovariectomy (Ovt, n=6) and Bortezomib (Bort, n=6) subgroups. Twelve weeks later, the rats were perfused. Then, uterine tissues were removed and examined by morphometrical, and light and electron microscopy methods. In addition, immunoreactivity of nuclear factor-kappa (NF-κB) was evaluated.

Results: Morphometric and histopathological evaluations showed that Bort was effective in the uterus and protects the layer structures and the cells.

Conclusion: In the light of these findings, we suggest that for proteasome inhibitor particularly Bort is thought to be useful through proteasome inhibition and NF-κB pathway.

Keywords: Bortezomib; Microscopy; Ovariectomy; Rat; Stereology; Uterus.

Figure 1

Images obtained from the uterus of the Cont group. Different sections of the endometrium, myometrium and perimetrium were in normal view. En, endometriyum; My, myometrium; Pr, perimetrium; Ep, epithelium; Lp, lamina propria

Figure 2

A-D indicate the images obtained from the uterus of the Ovt group’s. ♦, thinning of the epithelium; →, epithelial thinning; ► , proliferation in the blood vessels

Figure 3

A-D show the images obtained from the uterus of the Bort group’s. ►, proliferation of myometrium muscle cells. In D part, epithelium and stroma also draws attention to the healthy appearance

Figure 4

A and B are images obtained from the uterus of the Cont group. C and D are images obtained from the uterus of the Ovt group. In the C and D, in the endometrium, immune positivity was observed in connective tissue cells that forming the uterine stroma. → and ► show immune cells as epithelial and stromal positive staining. E and F are images obtained from the uterus of the Bort group. C shows intense cytoplasmic immune positivity in the stromal cells of the endometrium. D, capillary wall is observed positive immunostaining. → and ► respectively uterine epithelial surface and shows positive staining observed on the vessel wall. These representative images stained with anti-NF-kB immune peroxidase & Mayer hematoxylin.

Figure 5

A-D are the electron microscopic images which belonging to the Cont group of uterus. A, endometrial surface epithelium; B, complex of side face connections between epithelial cells; C and D, stromal cells and connective tissue fibers are regarded as healthy

Figure 6

A-D are the electron microscopic images which belonging to the uterus of the Ovt group. In A-D, degeneration observed in surface epithelium of endometrial and the side face of complex connections between epithelial cells it is monitored in detail. →, Shrunken and pyknotic appearance until the nuclei of epithelial cells. *; vessels in the stroma; #, irregular limited spaces in the stroma;►, thickened basement membrane; n, pushed to the edge shrunken and epithelial cell nucleus; →, deteriorated between epithelial cells and electrons shows the intercellular junctional complexes containing dense material. B and C show electron-dense organelle structure and epithelial cells with shrunken nucleus.

Figure 7

A-D notice that the electron microscopic images which belong to uterus of the Bort group. Surface epithelium of uterine and the endometrial stroma, it is mostly noteworthy healthy appearance. n, basal located nucleus of epithelial cell; *, intensive looking electrons, it shows prominent nuclei. B, intercellular connections, it draws attention to a healthy structure