Royal jelly alleviates gemcitabine-induced ovarian toxicity: an investigation on rat models.

BACKGROUND: Royal Jelly (RJ), an important product of apitherapy, has been traditionally used for its various health benefits, particularly for its anti-inflammatory, antioxidant, and immune-modulatory properties. RJ's ability to reduce oxidative stress, inflammation, and cellular damage has made it a promising candidate for preserving ovarian function and fertility during cancer treatments. Gemcitabine (GEM) is an antimetabolite chemotherapeutic drug known to cause ovarian toxicity. To date, there has been no study evaluating the protective effects of RJ specifically against GEM-induced ovarian damage, making this an original contribution to the field. This study investigated RJ's protective effects against GEM-induced ovarian toxicity in rats. METHOD: Thirty-two female Wistar-Albino rats were divided into four groups: Control, RJ, GEM, and GEM + RJ. GEM (200 mg/kg) was administered intraperitoneally, while RJ (100 mg/kg) was given orally for one week before GEM administration. Histopathological, immunohistochemical, and biochemical analyses were performed to assess ovarian tissue damage, inflammation, and oxidative stress markers. RESULTS: GEM treatment caused ovarian damage, including vascular congestion, vacuolization, and Hemorrhage. RJ partially suppressed GEM-induced increases in TNF-α, IL-1β, and IL-6 levels and enhanced AMH expression only in primary follicles. Additionally, RJ only partially lowered FSH levels while increasing LH levels. RJ also counteracted GEM-induced oxidative stress by reducing MDA levels and partially enhancing SOD and CAT activity. GEM caused ovarian damage, including vascular congestion, vacuolization, hemorrhage, inflammation, and oxidative stress. CONCLUSIONS: RJ partially reduced inflammatory response and oxidative stress, supported follicular development, increased AMH expression, and alleviated histopathological damage. This original study highlights the potential of RJ as a natural adjunct to preserve ovarian reserve during gemcitabine chemotherapy, while emphasizing the need for further research to determine its long-term effects and optimal dosage.