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Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate.

Oliva SU, Scarano WR, Okada FK, Miraglia SM - Reprod. Biol. Endocrinol. (2012)

Bottom Line: At the end of each treatment period, ventral prostates were removed and histologically processed.The prostate sections were submitted to the histopathological, morphological and stereological analyses using image analysis system.The results suggest a direct effect of the CBZ on rat ventral prostate, evidenced by increase of mast cell and macrophage populations during pre-puberty and puberty causing a ventral prostate accentuated damage in the adult phase.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Morphology and Genetics, Developmental Biology Laboratory, Federal University of São Paulo, Brazil.

ABSTRACT

Background: Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also used for the treatments of psychiatric disorders and neuropathic pain. The CBZ utilization has been associated with male reproductive damage, including hormonal alterations, sexual dysfunction and reduction of sperm quality. The wide and long-term use of the CBZ is a common schedule in children and adolescents and alters the testosterone level in adult rats and humans. The objective of this work was to evaluate the CBZ side effects on the ventral prostate of rats from pre-puberty to sexual maturation, since the prostate is an androgen-dependent organ.

Methods: Twenty three day-old male albino Wistar rats received CBZ diluted in propylene glycol (20 mg/Kg/i.p via). The treatment lasted 20, 40 and 70 days, according to the different stages of the rat sexual maturation. At the end of each treatment period, ventral prostates were removed and histologically processed. The prostate sections were submitted to the histopathological, morphological and stereological analyses using image analysis system.

Results: Reductions of the glandular epithelium, glandular lumen and fibromuscular stroma volume of the ventral prostate were observed in adult rats treated with CBZ since the weaning. Triggering and degranulation of mast cells were observed in the fibromuscular stroma of prepubertal and pubertal CBZ treated rats.

Conclusions: The results suggest a direct effect of the CBZ on rat ventral prostate, evidenced by increase of mast cell and macrophage populations during pre-puberty and puberty causing a ventral prostate accentuated damage in the adult phase.

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Photomicrographs of ventral prostate sections of CBZ-treated rats at different ages. Toluidine blue method. A: Part of ventral prostate sections of the CBZ93 rat showing the fibromuscular stroma with mast cells (arrows) around blood vessel (Bv). Bar: 20 μm. B and C: Ventral prostate sections of the CBZ63 rats. Note mast cells with fine cytoplasmatic granules (4b, head arrows), mast cells in degranulation process (4c, arrows) and cytoplasmatic granules (asterisks) distributed into the fibromuscular stroma. Bar: 18 μm and 11 μm, respectively.
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Figure 4: Photomicrographs of ventral prostate sections of CBZ-treated rats at different ages. Toluidine blue method. A: Part of ventral prostate sections of the CBZ93 rat showing the fibromuscular stroma with mast cells (arrows) around blood vessel (Bv). Bar: 20 μm. B and C: Ventral prostate sections of the CBZ63 rats. Note mast cells with fine cytoplasmatic granules (4b, head arrows), mast cells in degranulation process (4c, arrows) and cytoplasmatic granules (asterisks) distributed into the fibromuscular stroma. Bar: 18 μm and 11 μm, respectively.

Mentions: The sections of the rat ventral prostate of all control and CBZ-treated groups showed acini surrounded by a fibromuscular stroma, which frequently showed secretion within the lumen. In all groups, the mucosa of the ventral prostate was typically folded showing tall columnar secretory epithelial cells (Figures 3A, E). In the fibromuscular stroma, layers of smooth muscle fibers were observed involving the acini; outer and extensive connective tissue surrounded these structures (Figures 3A-F). Mast cells were found in the stroma of the control (Figures 3A, C, E) and CBZ-treated animals (Figures 3B, D, F and 4A-C). However, cytoplasm of mast cells showed accentuated granules in CBZ43 (Figure 3B) and CBZ63 groups (Figures 3D and 4B, C). Frequently, the granules appeared to be releasing into the connective tissue, suggesting an activation of the mast cells (Figure 3D and 4C). Nevertheless, the CBZ93 rats (Figure 3F) showed mast cells with similar morphological characteristics when compared to those of the C93 control group (Figure 3E). Moreover, the numerical density of mast cells was significantly higher in CBZ63 and CBZ93 groups in comparison to corresponding controls groups (Figure 5).


Harmful effects of carbamazepine on the postnatal development of the rat ventral prostate.

Oliva SU, Scarano WR, Okada FK, Miraglia SM - Reprod. Biol. Endocrinol. (2012)

Photomicrographs of ventral prostate sections of CBZ-treated rats at different ages. Toluidine blue method. A: Part of ventral prostate sections of the CBZ93 rat showing the fibromuscular stroma with mast cells (arrows) around blood vessel (Bv). Bar: 20 μm. B and C: Ventral prostate sections of the CBZ63 rats. Note mast cells with fine cytoplasmatic granules (4b, head arrows), mast cells in degranulation process (4c, arrows) and cytoplasmatic granules (asterisks) distributed into the fibromuscular stroma. Bar: 18 μm and 11 μm, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3344685&req=5

Figure 4: Photomicrographs of ventral prostate sections of CBZ-treated rats at different ages. Toluidine blue method. A: Part of ventral prostate sections of the CBZ93 rat showing the fibromuscular stroma with mast cells (arrows) around blood vessel (Bv). Bar: 20 μm. B and C: Ventral prostate sections of the CBZ63 rats. Note mast cells with fine cytoplasmatic granules (4b, head arrows), mast cells in degranulation process (4c, arrows) and cytoplasmatic granules (asterisks) distributed into the fibromuscular stroma. Bar: 18 μm and 11 μm, respectively.
Mentions: The sections of the rat ventral prostate of all control and CBZ-treated groups showed acini surrounded by a fibromuscular stroma, which frequently showed secretion within the lumen. In all groups, the mucosa of the ventral prostate was typically folded showing tall columnar secretory epithelial cells (Figures 3A, E). In the fibromuscular stroma, layers of smooth muscle fibers were observed involving the acini; outer and extensive connective tissue surrounded these structures (Figures 3A-F). Mast cells were found in the stroma of the control (Figures 3A, C, E) and CBZ-treated animals (Figures 3B, D, F and 4A-C). However, cytoplasm of mast cells showed accentuated granules in CBZ43 (Figure 3B) and CBZ63 groups (Figures 3D and 4B, C). Frequently, the granules appeared to be releasing into the connective tissue, suggesting an activation of the mast cells (Figure 3D and 4C). Nevertheless, the CBZ93 rats (Figure 3F) showed mast cells with similar morphological characteristics when compared to those of the C93 control group (Figure 3E). Moreover, the numerical density of mast cells was significantly higher in CBZ63 and CBZ93 groups in comparison to corresponding controls groups (Figure 5).

Bottom Line: At the end of each treatment period, ventral prostates were removed and histologically processed.The prostate sections were submitted to the histopathological, morphological and stereological analyses using image analysis system.The results suggest a direct effect of the CBZ on rat ventral prostate, evidenced by increase of mast cell and macrophage populations during pre-puberty and puberty causing a ventral prostate accentuated damage in the adult phase.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Morphology and Genetics, Developmental Biology Laboratory, Federal University of São Paulo, Brazil.

ABSTRACT

Background: Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also used for the treatments of psychiatric disorders and neuropathic pain. The CBZ utilization has been associated with male reproductive damage, including hormonal alterations, sexual dysfunction and reduction of sperm quality. The wide and long-term use of the CBZ is a common schedule in children and adolescents and alters the testosterone level in adult rats and humans. The objective of this work was to evaluate the CBZ side effects on the ventral prostate of rats from pre-puberty to sexual maturation, since the prostate is an androgen-dependent organ.

Methods: Twenty three day-old male albino Wistar rats received CBZ diluted in propylene glycol (20 mg/Kg/i.p via). The treatment lasted 20, 40 and 70 days, according to the different stages of the rat sexual maturation. At the end of each treatment period, ventral prostates were removed and histologically processed. The prostate sections were submitted to the histopathological, morphological and stereological analyses using image analysis system.

Results: Reductions of the glandular epithelium, glandular lumen and fibromuscular stroma volume of the ventral prostate were observed in adult rats treated with CBZ since the weaning. Triggering and degranulation of mast cells were observed in the fibromuscular stroma of prepubertal and pubertal CBZ treated rats.

Conclusions: The results suggest a direct effect of the CBZ on rat ventral prostate, evidenced by increase of mast cell and macrophage populations during pre-puberty and puberty causing a ventral prostate accentuated damage in the adult phase.

Show MeSH
Related in: MedlinePlus