Involvement of PTEN and FOXO3a Proteins in the Protective Activity of Protocatechuic Acid Against Cisplatin-Induced Ovar
- PDF / 2,995,119 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 61 Downloads / 168 Views
ORIGINAL ARTICLE
Involvement of PTEN and FOXO3a Proteins in the Protective Activity of Protocatechuic Acid Against Cisplatin-Induced Ovarian Toxicity in Mice Bruna Bortoloni Gouveia 1 & Ricássio de Sousa Barberino 1 & Regina Lucia dos Santos Silva 1 & Thae Lanne Barbosa Gama Lins 1 & Valéria da Silva Guimarães 1 & Alane Pains Oliveira do Monte 1 & Raimundo Campos Palheta Jr 2 & Maria Helena Tavares de Matos 1,3 Received: 12 January 2020 / Accepted: 25 August 2020 # Society for Reproductive Investigation 2020
Abstract 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. Keywords Oxidative stress . Ovary . Fertility preservation . Premature ovarian failure . Protein kinase
Introduction * Maria Helena Tavares de Matos [email protected] 1
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina, PE 56300-990, Brazil
2
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, PE 56300-990, Brazil
3
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
Cisplatin (cis-diaminodichloroplatin II) is on
Data Loading...
