leaf extract protects against cisplatin-induced ovarian damage through regulation of p-PTEN and p-Akt proteins in mice.

Objectives: To evaluate the effects of leaf extract against cisplatin-induced ovarian toxicity in mice and involvement of p-PTEN and p-Akt proteins.

Materials And Methods: 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) acetylcysteine (positive control), with (4) 50, or (5) 200 mg/kg body weight of 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 extract could prevent cisplatin-induced ovarian damage.

Results: After HPLC analysis, protocatechuic acid was detected in the extract. The pretreatment with -acetylcysteine or 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 extract regulated p-PTEN and p-Akt immunoexpression after cisplatin exposure.

Conclusion: Pretreatment with extract prevented cisplatin-induced ovarian damage through its anti-oxidant actions and by modulating the expression of phosphorylated PTEN and Akt proteins.