Effects of treatment with clinically relevant valproate, carbamazepine, oxcarbazepine, topiramate, lamotrigine and levetiracetam on ovarian folliculogenesis in young rats

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dc.contributor.authorCansu A.
dc.contributor.authorGurgen S.G.
dc.contributor.authorDemirhan Y.N.
dc.contributor.authorOzkan Kart P.
dc.contributor.authorYildirim M.
dc.contributor.authorAlver A.
dc.contributor.authorYeni̇lmez E.
dc.contributor.authorSönmez F.M.
dc.date.accessioned2024-07-22T08:04:19Z
dc.date.available2024-07-22T08:04:19Z
dc.date.issued2022
dc.description.abstractAim: To determine the effects of valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV) on ovarian folliculogenesis in young rats. Methods: Forty-nine female Wistar rats, aged 21–24 days, were divided equally into 7 experimental groups. These were given tap water over 21–24 days (control group), 300 mg/kg of VPA, 150 mg/kg of CBZ, 150 mg/kg of OXC, 100 mg/kg of TPM, 10 mg/kg of LTG, or 50 mg/kg of LEV daily in 2 doses via oral gavage until the end of puberty. At the end of the study, the estrous cycle of each rat was monitored daily, and those rats in pro-estrus or di-estrus were sacrificed and the ovaries removed. Serial sections obtained from the ovaries were stained with hematoxylin and eosin, and the corpora lutea and follicles were enumerated. Apoptotic cells were detected using the TUNEL technique. Various serial sections were immunohistochemically stained with proliferating cell nuclear antigen (PCNA), growth differentiation factor (GDF)-9, caspase-3, caspase-9, transforming growth factor beta 1 (TGF-1), and epidermal growth factor (EGF), and evaluated and photographed under a light microscope. Key Findings: The number of corpora lutea was significantly increased in the VPA, CBZ, OXC, and LTG groups compared to the control group (p < 0.001). The number of TUNEL-positive ovarian follicles was 3.3 ± 1.1 (median, 3), 6.1 ± 0.9 (median, 6), and 5.7 ± 0.8 (median,6) in the control, OXC and LEV groups, respectively (p < 0.001). The number of TUNEL-positive granulosa cells was higher in all the groups treated with antiepileptics, with the exception of the TPM group, compared to the control group (p < 0.001). HSCOREs for immunohistochemical staining using PCNA, GDF-9, TGF-1 and EGF were significantly higher in the control group than in the others (p < 0.001). HSCORE for staining using caspase-3 was significantly higher in the VPA, CBZ, OXC and LEV groups, while the HSCORE was significantly lower in the TPM group than in the control group. HSCORE for staining using caspase-9 was significantly higher in the VPA, CBZ and OXC groups, while it was significantly lower in the TPM group than in the control group (p < 0.001). Significance: Exposure to VPA, CBZ, OXC, TPM, LTG and LEV caused different levels of impaired folliculogenesis in young rats. © 2022 Elsevier B.V.
dc.identifier.DOI-ID10.1016/j.eplepsyres.2022.106966
dc.identifier.issn09201211
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/12654
dc.language.isoEnglish
dc.publisherElsevier B.V.
dc.subjectAnimals
dc.subjectAnticonvulsants
dc.subjectBenzodiazepines
dc.subjectCarbamazepine
dc.subjectCaspase 3
dc.subjectCaspase 9
dc.subjectEpidermal Growth Factor
dc.subjectFemale
dc.subjectLamotrigine
dc.subjectLevetiracetam
dc.subjectOvary
dc.subjectOxcarbazepine
dc.subjectProliferating Cell Nuclear Antigen
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectTopiramate
dc.subjectValproic Acid
dc.subjectcarbamazepine
dc.subjectcaspase 3
dc.subjectcaspase 9
dc.subjectcycline
dc.subjecteosin
dc.subjectepidermal growth factor
dc.subjectgrowth differentiation factor 9
dc.subjecthematoxylin
dc.subjectlamotrigine
dc.subjectlevetiracetam
dc.subjectoxcarbazepine
dc.subjecttap water
dc.subjecttopiramate
dc.subjecttransforming growth factor beta1
dc.subjectvalproic acid
dc.subjectanticonvulsive agent
dc.subjectbenzodiazepine derivative
dc.subjectcarbamazepine
dc.subjectcaspase 3
dc.subjectcaspase 9
dc.subjectcycline
dc.subjectepidermal growth factor
dc.subjectlamotrigine
dc.subjectlevetiracetam
dc.subjectoxcarbazepine
dc.subjecttopiramate
dc.subjectvalproic acid
dc.subjectadult
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcell count
dc.subjectcontrolled study
dc.subjectcorpus luteum
dc.subjectestrus cycle
dc.subjectfemale
dc.subjectgranulosa cell
dc.subjectimmunohistochemistry
dc.subjectimmunoreactivity
dc.subjectmicroscopy
dc.subjectnonhuman
dc.subjectovary follicle
dc.subjectovary follicle development
dc.subjectprepuberty
dc.subjectrat
dc.subjectstaining
dc.subjectTUNEL assay
dc.subjectWistar rat
dc.subjectyoung adult
dc.subjectanimal
dc.subjectovary
dc.titleEffects of treatment with clinically relevant valproate, carbamazepine, oxcarbazepine, topiramate, lamotrigine and levetiracetam on ovarian folliculogenesis in young rats
dc.typeArticle

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