Neuroprotective effects of eugenol against aluminium-induced toxicity in the rat brain

Abstract

Aluminium (Al) is a neurotoxic metal that contributes to the progression of several neurodegenerative diseases. The aim of the present study was to evaluate the protective effect of dietary eugenol supplementation against aluminium (Al)-induced cerebral damage in rats. Male Wistar rats were divided into four groups: normal controls, rats fed a diet containing 6,000 μg g^-1 eugenol, rats intoxicated daily with aluminium chloride (84 mg kg^-1 body weight) p. o. and fed either a basal diet or a eugenol-containing diet. Daily oral administration of Al for four consecutive weeks to rats significantly reduced brain total antioxidant status (TAS) (11.42±0.31 μmol g^-1 tissue, p<0.001) with a subsequent significant enhancement of lipid peroxidation (MDA) (32.55±1.68 nmol g^-1 tissue, p<0.002). In addition, Al enhanced brain acetylcholinesterase activity (AChE) (46.22±4.90 U mg^-1 protein, p<0.001), tumour necrosis factor alpha (TNF-α) (118.72±11.32 pg mg^-1 protein, p<0.001), and caspase 3 (Casp-3) (8.77±1.26 ng mg^-1 protein, p<0.001) levels, and in contrast significantly suppressed brain-derived neurotrophic factor (BDNF) (82.74±14.53 pg mg^-1 protein, p<0.002) and serotonin (5-HT) (1.54±0.12 ng mg^-1 tissue, p<0.01) levels. Furthermore, decreased glial fibrillary acidic protein (GFAP) immunostaining was noticed in the striatum of Al-intoxicated rats, compared with untreated controls. On the other hand, co-administration of dietary eugenol with Al intoxication restored brain BDNF (108.76±2.64 pg mg^-1 protein) and 5-HT (2.13±0.27 ng mg^-1 tissue) to normal levels, enhanced brain TAS (13.43±0.24 μmol g^-1 tissue, p<0.05), with a concomitant significant reduction in TNF-α (69.98±4.74 pg mg^-1 protein) and Casp-3 (3.80±0.37 ng mg^-1 protein) levels (p<0.001), as well as AChE activity (24.50±3.25 U mg^-1 protein, p<0.001), and increased striatal GFAP immunoreactivity, compared with Al-treated rats. Histological findings of brain tissues verified biochemical data. In conclusion, eugenol holds potential as a neuroprotective agent through its hydrophobic, antioxidant, and anti-apoptotic properties, as well as its neurotrophic ability against Al-induced brain toxicity in rats.