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

Area of Science:

• Reproductive Toxicology
• Natural Product Chemistry
• Molecular Biology

Background:

• Cisplatin (CP) chemotherapy is associated with significant testicular toxicity, a major concern for male reproductive health.
• Alpha-pinene (AP), a plant-derived monoterpene, possesses known antioxidant properties.
• The nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway plays a crucial role in cellular defense against oxidative stress.

Purpose of the Study:

• To investigate the therapeutic efficacy of alpha-pinene (AP) in ameliorating cisplatin (CP)-induced testicular toxicity in a rat model.
• To elucidate the role of the Nrf2 pathway in the protective mechanism of AP against CP-induced testicular damage.

Main Methods:

• Male rats were divided into control, CP-treated, CP + AP-treated (two doses), and AP-only groups.
• CP was administered to induce testicular toxicity, followed by AP treatment.
• Serum reproductive hormones, testicular oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis markers, and Nrf2 pathway activation were assessed.

Main Results:

• Cisplatin administration significantly elevated markers of oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis in testicular tissue.
• Alpha-pinene treatment dose-dependently ameliorated these CP-induced detrimental effects.
• Histological analysis confirmed the protective effects of AP, and mechanistic studies indicated Nrf2 pathway induction by AP.

Conclusions:

• Alpha-pinene demonstrates significant therapeutic potential in counteracting cisplatin-induced testicular toxicity.
• AP may serve as a valuable therapeutic agent to mitigate chemotherapy-induced reproductive toxicity, potentially through Nrf2 pathway activation.