Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells

Abstract

SUMMARYPurpose: To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells. Methods: Fifty-six female prepubertal Wistar rats (21-24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques. Results: In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 ± 1.32 in controls, and significantly increased to 29.60 ± 1.58, 34.20 ± 2.53, and 54.80 ± 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group. Conclusion: VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.

Effects of chronic treatment with valproate and oxcarbazepine on testicular development in rats

“…To the best of our knowledge, the literature contains no studies on the histopathological change in the testis tissue caused by OXC. This study demonstrates that in contrast to the negative effects in female rat ovarian tissues caused by OXC, 25,26 it does not lead to prominent changes in spermatogenetic cells and stages in male rats.…”

“…Three more recent studies have reported that OXC causes edema and apoptosis in retinal ganglion cells, and ovarian and endometrial tissues. 25,26,31 OXC gives rise to swelling and edema in some cells, leading to impairment and subsequent apoptosis and cell death in cell organelles. This particularly occurs in more aged cells.…”

Possible Anticancer Activity of Rosuvastatine, Doxazosin, Repaglinide and Oxcarbazepin

“…It was reported that it had an apoptotic and degenerative effects on rat uterine and ovarian cells (Cansu et al, 2010).…”

Reduction in Valproic Acid–Induced Neural Tube Defects by Maternal Immune Stimulation: Role of Apoptosis

“…Di Renzo et al () showed a relationship between axial skeletal malformations and increased apoptosis in somites caused by VA exposure in CD‐1 mice. VA has also been shown to cause apoptosis of uterine and ovarian cells in rats (Cansu et al., ). In embryo culture, VA caused oxidative stress and led to increased cell death (Tung and Winn, ).…”