Cycloastragenol Attenuates Cisplatin-Induced Ovarian Toxicity in Rats: Associations With TERT Expression, Apoptotic Balance, and FOXO3a-mTOR-Related Signaling.
- 1Department of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara, Türkiye.
- 2Department of Medical Biology, Faculty of Medicine, Gazi University, Ankara, Türkiye.
Abstract
Cisplatin (CIS)-induced ovarian toxicity is characterized by follicular depletion, apoptosis, and disruption of intracellular survival signaling. This study investigated whether cycloastragenol (CAG), a telomerase-associated bioactive compound, attenuates CIS-induced ovarian injury in rats. Forty female Sprague-Dawley rats were assigned to two vehicle-control groups and CAG, CIS, or CIS + CAG groups for 15 days. Vehicle controls were pooled after confirming no significant differences. Ovarian morphology and follicle counts were evaluated histologically. Immunohistochemical analyses included PCNA, caspase-3, total FOXO3a, phospho-FOXO3a (Ser253), total mTOR, BAX, BCL-2, and TERT. Serum anti-Müllerian hormone and telomerase-related measurements were assessed by ELISA, and relative telomere length was determined by quantitative real-time PCR. CIS reduced primordial follicle numbers, increased follicular atresia, enhanced BAX expression, reduced BCL-2 and TERT immunoreactivity, and increased the BAX/BCL-2 ratio. CAG co-treatment significantly attenuated the changes in BAX, BCL-2, the BAX/BCL-2 ratio, and TERT. Nuclear phospho-FOXO3a was significantly lower in the CIS + CAG group than in the CIS group, whereas cytoplasmic phospho-FOXO3a did not differ significantly. Total mTOR and caspase-3 were numerically reduced by CAG co-treatment but did not remain significant after multiple-comparison correction. PCNA, total FOXO3a, and serum AMH showed partial or nonsignificant recovery. Relative telomere length did not differ among groups. CAG partially attenuated CIS-induced ovarian injury and apoptotic imbalance and was associated with restoration of ovarian TERT immunoreactivity and modulation of phospho-FOXO3a localization. However, these findings do not establish a causal telomerase-FOXO3a-mTOR mechanism.
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BibTeX
@article{erol2026cycloastragenol,
title = {{Cycloastragenol Attenuates Cisplatin-Induced Ovarian Toxicity in Rats: Associations With TERT Expression, Apoptotic Balance, and FOXO3a-mTOR-Related Signaling.}},
author = {Gökçe Nur Arık Erol and Atiye Seda Yar and Gülnur Take Kaplanoğlu},
journal = {Journal of biochemical and molecular toxicology},
year = {2026},
month = oct,
doi = {10.1002/jbt.71152},
url = {https://europepmc.org/article/MED/42927619},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cycloastragenol Attenuates Cisplatin-Induced Ovarian Toxicity in Rats: Associations With TERT Expression, Apoptotic Balance, and FOXO3a-mTOR-Related Signaling.
AU - Gökçe Nur Arık Erol
AU - Atiye Seda Yar
AU - Gülnur Take Kaplanoğlu
PY - 2026
DA - 2026/10/30
JO - Journal of biochemical and molecular toxicology
DO - 10.1002/jbt.71152
UR - https://europepmc.org/article/MED/42927619
AB - Cisplatin (CIS)-induced ovarian toxicity is characterized by follicular depletion, apoptosis, and disruption of intracellular survival signaling. This study investigated whether cycloastragenol (CAG), a telomerase-associated bioactive compound, attenuates CIS-induced ovarian injury in rats. Forty female Sprague-Dawley rats were assigned to two vehicle-control groups and CAG, CIS, or CIS + CAG groups for 15 days. Vehicle controls were pooled after confirming no significant differences. Ovarian morphology and follicle counts were evaluated histologically. Immunohistochemical analyses included PCNA, caspase-3, total FOXO3a, phospho-FOXO3a (Ser253), total mTOR, BAX, BCL-2, and TERT. Serum anti-Müllerian hormone and telomerase-related measurements were assessed by ELISA, and relative telomere length was determined by quantitative real-time PCR. CIS reduced primordial follicle numbers, increased follicular atresia, enhanced BAX expression, reduced BCL-2 and TERT immunoreactivity, and increased the BAX/BCL-2 ratio. CAG co-treatment significantly attenuated the changes in BAX, BCL-2, the BAX/BCL-2 ratio, and TERT. Nuclear phospho-FOXO3a was significantly lower in the CIS + CAG group than in the CIS group, whereas cytoplasmic phospho-FOXO3a did not differ significantly. Total mTOR and caspase-3 were numerically reduced by CAG co-treatment but did not remain significant after multiple-comparison correction. PCNA, total FOXO3a, and serum AMH showed partial or nonsignificant recovery. Relative telomere length did not differ among groups. CAG partially attenuated CIS-induced ovarian injury and apoptotic imbalance and was associated with restoration of ovarian TERT immunoreactivity and modulation of phospho-FOXO3a localization. However, these findings do not establish a causal telomerase-FOXO3a-mTOR mechanism.
SN - 1095-6670
SN - 1099-0461
ER -