Protective effects of hesperidin against nano-alumina in the rat brain: Bioaccumulation, oxidative stress, and inflammatory biomarkers

The protective efficiency of hesperidin (Hesp) against the bioaccumulation and neurotoxicity induced by nano-alumina (Al 2 O 3 NPs) in three brain regions (BR), hippocampus (Hippo), cortex (Cor), and brainstem (BS), has been investigated in rats. The study comprised a 30-day pre-treatment period followed by 7- and 14-days experimental periods (EP) of treatments (T). Rats were divided into four groups: Group I received de-ionized water (DW) daily via both intranasal and oral routes throughout the pre-treatment and T. Group II was administered intranasal DW daily during the pre-treatment period, followed by intranasal Al 2 O 3 NPs every other day during the T. Group III was administered oral Hesp daily during both the pre-treatment and T. Group IV received a daily oral Hesp during the pre-treatment. During the T, rats were given an intranasal Al 2 O 3 NPs every other day alongside a daily oral dose of Hesp. Animal sacrifice and tissue collection occurred on day 7 and day 14 of the T. The results showed a significant increase in aluminum (Al 3+ ) ion accumulation in all BR of Group II as compared with the three other groups. In Group II, the levels of iron (Fe 2+ ), zinc (Zn 2+ ), glutathione (GSH), as well as the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly decreased. Tumor necrosis factor-alfa (TNF-α) and interleukin-6 (IL-6) were markedly elevated in this group. Significant inverse correlations were observed between Al 3+ ion accumulation and the levels of Fe 2+ , Zn 2+ , GSH, as well as the activities of SOD and CAT. In contrast, a significant positive correlation was found between Al 3+ accumulation and TNF-α and IL-6 levels. In conclusion, co-administration of Hesp with Al 2 O 3 NPs reduced the neurotoxic effects of Al 2 O 3 NPs. The present findings suggest that Hesp protected against Al 2 O 3 NPs-induced neurotoxicity by limiting Al 3+ ion bioaccumulation, thereby alleviating oxidative stress and inflammation.