Involvement of PTEN and FOXO3a Proteins in the Protective Activity of Protocatechuic Acid Against Cisplatin-Induced Ovarian Toxicity in Mice.

Autor: Gouveia BB; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., Barberino RS; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., Dos Santos Silva RL; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., Lins TLBG; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., da Silva Guimarães V; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., do Monte APO; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., Palheta RC Jr; Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil., de Matos MHT; Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE, 56300-990, Brazil. helena.matos@univasf.edu.br.; Colegiado de Medicina Veterinária - Laboratório de Biologia Celular, Citologia e Histologia, Universidade Federal do Vale do São Francisco (UNIVASF), Rodovia BR 407, Km 12, Lote 543 - Projeto de Irrigação Nilo Coelho - S/N, C1., Petrolina, PE, 56300-990, Brazil. helena.matos@univasf.edu.br.
Jazyk: angličtina
Zdroj: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2021 Mar; Vol. 28 (3), pp. 865-876. Date of Electronic Publication: 2020 Nov 10.
DOI: 10.1007/s43032-020-00305-4
Abstrakt: The present study evaluated the effects of protocatechuic acid (PCA) after cisplatin-induced ovarian toxicity in mice and if PTEN and FOXO3a proteins are involved in PCA action. The mice were divided into five experimental groups (five animals per group) and treated once a day for 3 days as follows: (1) the control group was pretreated with oral administration (o.p.) of saline solution, followed by an intraperitoneal (i.p.) injection of saline solution. The other groups were pretreated (o.p.) with (2) saline solution (cisplatin group), (3) N-acetylcysteine (150 mg/kg of body weight), or with (4) 20 or (5) 50 mg/kg body weight of PCA, followed by 5 mg/kg body weight (i.p.) of cisplatin. Next, the ovaries were destined to histological (morphology and activation), immunohistochemical (PCNA and cleaved caspase-3 expression), and fluorescence (reactive oxygen species [ROS], glutathione [GSH], and active mitochondria levels) analyses. Moreover, the immunoreactivity for p-PTEN and p-FOXO3a was evaluated to investigate a potential mechanism by which PCA could prevent the cisplatin-induced ovarian damage. Pretreatment with N-acetylcysteine or 20 mg/kg PCA before cisplatin preserved the percentage of normal follicles and cell proliferation as observed in the control, reduced apoptosis and ROS levels, and showed higher active mitochondria and GSH levels than the cisplatin treatment (P < 0.05). Moreover, pretreatment with 20 mg/kg PCA decreased cisplatin-induced p-PTEN and increased (P < 0.05) nuclear export of p-FOXO3a. In conclusion, PCA at 20 mg/kg reduced apoptosis, maintained cell proliferation and mitochondrial function, reduced ROS production, and increased GSH expression likely through the involvement of PTEN and FOXO3a proteins.
Databáze: MEDLINE