Neuroprotective Synergy Of Quercetin And Rutin In Mitigating Aluminum Chloride-Induced Mitochondrial Oxidative Damage: An In Vitro Approach

Abstract

Aluminum (Al), the third most abundant element in the Earth's crust, induces neurotoxicity primarily through oxidative stress mechanisms and mitochondrial dysfunction. This study investigated the neuroprotective potential of two flavonoids, quercetin and rutin, against aluminum chloride (AlCl₃)-induced oxidative damage in isolated rat brain mitochondria. Brain mitochondria were isolated from five male Wistar rats and allocated to four experimental groups: control, AlCl₃-exposed (2 mg/L), AlCl₃ + quercetin (0.1 mg/L), and AlCl₃ + rutin (0.2 mg/L). All groups were incubated for 2, 6, and 20 hours to evaluate time-dependent effects.

After 20 hours of incubation, AlCl₃ exposure significantly increased lipid peroxidation (MDA levels, +104.28%) and decreased antioxidant enzyme activities (CAT: -21.98%, SOD: -34.43%, GST: -30.56%), indicating substantial oxidative stress induction. Mitochondrial respiratory chain analysis revealed marked impairment of complexes I/III (-76.60%) and IV (-37.00%). Co-administration of quercetin attenuated MDA elevation (+87.37% vs. +104.28% with AlCl₃ alone) while showing differential effects on antioxidant enzymes. Notably, quercetin significantly enhanced complex IV activity (+86.52%) despite further reduction in complexes I/III activity (-84.81%). Similarly, rutin treatment more effectively reduced lipid peroxidation (+50.31%) and provided partial protection of antioxidant enzyme activities, with moderate restoration of complex IV activity (+15.35%).

At earlier timepoints (2h, 6h), both flavonoids demonstrated distinct modulatory patterns on antioxidant enzymes, with transient upregulation of SOD and GST activities, suggesting dynamic temporal responses. These findings demonstrate that quercetin and rutin exert neuroprotective effects against aluminum-induced mitochondrial dysfunction through differential mechanisms, with quercetin showing stronger protection of complex IV activity while rutin more effectively mitigates lipid peroxidation.