Krill Oil Mitigates Cisplatin-Induced Ovarian Toxicity via Attenuation of Oxidative Stress and Inflammatory Pathways

Cisplatin remains a cornerstone chemotherapeutic agent; however, its off-target gonadotoxicity poses a significant risk for premature ovarian failure (POF) and infertility in young women. Strategies to preserve ovarian function during chemotherapy are critically needed. To investigate the protective effects of krill oil supplementation against cisplatin-induced ovarian damage in a rat model, with a focus on oxidative stress, inflammation, follicular dynamics, and stromal fibrosis. Twenty-one adult female Wistar albino rats were randomized into three groups: control, cisplatin-treated, and cisplatin + krill oil-treated. Ovarian toxicity was induced via intraperitoneal injection of cisplatin (2.5 mg/kg, twice weekly for four weeks). Krill oil (4 mL/kg/day) was administered orally during the same period. Ovarian histopathology, follicle counts (primordial, primary, secondary, tertiary), stromal fibrosis, and biochemical markers, including plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and ovarian levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Toll-like receptor 4 (TLR4), TNF-α, NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-1β were evaluated. Cisplatin significantly reduced primordial, primary, secondary, and tertiary follicle counts while increasing stromal fibrosis (p < 0.001). Krill oil co-treatment notably ameliorated follicular depletion—improving follicle counts by 38.16%, 54.74%, 62.5%, 40.43%, respectively—and reduced fibrosis (p = 0.017). Biochemically, cisplatin decreased AMH levels and Nrf2 expression while elevating MDA, TNF-α, TLR4, NLRP3, and IL-1β levels (p < 0.001). Krill oil supplementation restored AMH (p = 0.002) and Nrf2 (p = 0.003) levels, while reducing MDA (p = 0.009), NLRP3 (p < 0.001), ovarian IL-1β (p = 0.005), plasma IL-1β (p < 0.001), TLR4 (p = 0.001), plasma TNF-α (p = 0.001), and ovarian TNF-α (p < 0.001), compared to the cisplatin group. Krill oil exerts significant antioxidant and anti-inflammatory effects, offering a promising strategy to mitigate cisplatin-induced ovarian damage and preserve fertility in young cancer patients.