Alpha-pinene neutralizes cisplatin-induced reproductive toxicity in male rats through activation of Nrf2 pathway

Abstract

Purpose Testicular toxicity is one of the most important side efects of cisplatin (CP) therapy. Alpha-pinene (AP) is a naturally occurring monoterpene with antioxidant character in plants. Here, we aimed to evaluate the therapeutic activity of AP against CP-induced testicular toxicity by including the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway in rats. Methods Thirty male rats were divided into 5 groups: control, CP, CP+ AP (5 and 10 mg/kg) and only AP (10 mg/kg). CP was administered intraperitoneally at a dose of 5 mg/kg on the frst day, followed by three consecutive injections of AP. Serum reproductive hormone levels were evaluated using ELISA kits. Oxidative stress (OS), infammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were also determined colorimetrically. In addition, how CP afects Nrf2 pathway and the efect of AP on this situation were also addressed. Results Treatment with CP signifcantly increased OS, infammation, ERS and apoptosis in testicular tissue. Administrations of AP resulted in an amelioration of these altered parameters. The mechanism of therapeutic efect of AP appeared to involve induction of Nrf2. Furthermore, these results were also confrmed by histological data. Conclusion Results suggest that AP can exhibit therapeutic efects against CP-induced testicular toxicity. It can be concluded that AP may be a potential molecule to abolish reproductive toxicity after chemotherapy