Amburana cearensis leaf extract protects against cisplatin-induced ovarian damage through regulation of p-PTEN and p-Akt proteins in mice
نویسندگان
1 Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
2 Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
3 Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
4 Center for Drug, Medicament and Food Analysis, Department of Pharmacy, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
5 Center for Studies and Research of Medicinal Plants, Department of Pharmacy, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
6 Center for Studies and Research of Medicinal Plants, Department of Pharmacy, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
7 Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco,Brazil
8 Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
9 Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
10 Center for Drug, Medicament and Food Analysis, Department of Pharmacy, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
11 Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
doi
10.22038/ijbms.2022.58927.13092چکیده
Objective(s): To evaluate the effects of Amburana cearensis leaf extract against cisplatin-induced ovarian toxicity in mice and involvement of p-PTEN and p-Akt proteins. Materials and Methods: A. cearensis ethanolic leaf extract was analyzed by high-performance liquid chromatography (HPLC). Mice were pretreated once daily for 3 days as follows: (1) the control group was pretreated with oral administration (o.p.) of saline solution, followed by intraperitoneal (IP) injection of saline solution. The other groups were pretreated (o.p.) with (2) saline solution (cisplatin group), (3) N-acetylcysteine (positive control), with (4) 50, or (5) 200 mg/kg body weight of A. cearensis extract, followed by injection of 5 mg/kg body weight (IP) of cisplatin. The ovaries were harvested and destined for histological (follicular morphology), immunohistochemistry (apoptosis and cell proliferation), and fluorescence (reactive oxygen species [ROS], glutathione concentrations [GSH], and active mitochondria) analyses. Furthermore, immunoexpression of p-PTEN and p-Akt was evaluated to elucidate a potential mechanism by which A. cearensis extract could prevent cisplatin-induced ovarian damage. Results: After HPLC analysis, protocatechuic acid was detected in the extract. The pretreatment with N-acetylcysteine or A. cearensis extract maintained the percentage of normal follicles and cell proliferation, reduced apoptosis and ROS concentrations, and increased GSH concentrations and mitochondrial activity compared with cisplatin treatment. Furthermore, pretreatment with A. cearensis extract regulated p-PTEN and p-Akt immunoexpression after cisplatin exposure. Conclusion: Pretreatment with A. cearensis extract prevented cisplatin-induced ovarian damage through its anti-oxidant actions and by modulating the expression of phosphorylated PTEN and Akt proteins.