Neuroprotective effects of luteolin against aluminum-induced brain injury via chelation and antioxidant pathways.

Aluminum (Al) is a widespread environmental neurotoxin linked to several neurodegenerative conditions through oxidative stress, inflammation, and apoptosis. Because it is present in food, water, pharmaceuticals, and consumer products, chronic exposure is nearly unavoidable and poses a public health concern. Luteolin (LUT), a natural flavone with antioxidant, anti-inflammatory, and metal-chelating properties, has emerged as a potential neuroprotective agent. This study investigated the protective effects of LUT against aluminum chloride (AlCl3)-induced neurotoxicity in rats. Sprague-Dawley rats received AlCl3 (4.2 mg/kg, i.p.) alone or together with LUT (25 or 50 mg/kg, p.o.) for 30 days. Behavioral performance was evaluated using novel object recognition and open-field tests. ICP-MS was employed to quantify brain Al levels, and complementary analyses were conducted to assess oxidative stress, neuroinflammation, apoptosis-related gene expression, neuroplasticity markers (BDNF, c-Fos), and cholinergic function (AChE). AlCl3 exposure significantly increased brain Al accumulation and induced oxidative stress, inflammation, apoptosis, and behavioral deficits. Although LUT co-treatment led to an apparent increase in total brain Al, this rise is likely attributable to the formation of Al-LUT complexes. This interpretation is supported by the marked reduction in Al-induced oxidative stress, apoptosis, and inflammation, accompanied by improved behavioral outcomes. This evaluation reveals that LUT provides protection in an environmental Al neurotoxicity model, offering insights beyond classical Alzheimer's disease contexts. Although its antioxidant and anti-inflammatory effects are well documented, evidence for its efficacy against environmentally induced Al neurotoxicity is still lacking.