Protective effects of caffeine on aluminum-induced ovarian toxicity in a mouse model.

This study investigated the protective effects of caffeine (Caf) against aluminum chloride (AlCl₃)-induced ovarian toxicity in female Swiss Albino mice. Twenty-four adult female mice were equally divided into four groups (n = 6): control, Caf (40 mg/kg, oral), AlCl₃ (50 mg/kg, i.p.), and AlCl₃ + Caf, administered for seven consecutive days. AlCl₃ administration was associated with oxidative stress, as indicated by decreased ovarian glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels, along with increased malondialdehyde (MDA) levels. Caf pretreatment appeared to restore antioxidant enzyme activities and attenuate lipid peroxidation. Serum caspase-3 and caspase-9 levels were elevated following AlCl₃ administration, whereas Caf pretreatment was associated with reduced caspase levels. AlCl₃ exposure also led to increased serum interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α) levels. Histopathological examination revealed granulosa cell degeneration, follicular atresia, disruption of the corona radiata, and reduced follicle numbers in the AlCl₃ group, whereas Caf appeared to alleviate these lesions, as confirmed by histopathological scoring and follicle counts. Immunohistochemical analyses demonstrated reduced anti-Müllerian hormone (AMH) and AMH receptor 2 (AMHR2) expression and increased caspase-3 immunoreactivity following AlCl₃ exposure. Caf pretreatment was associated with increased AMH and AMHR2 expression and reduced caspase-3 immunoreactivity. These findings suggest that Caf may exert protective effects against AlCl₃-induced ovarian injury, potentially through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.