3-hydroxy-3′,4′,5′-trimethoxyflavone protects rats against lead-induced neurotoxicity via chelation and modulating oxidative stress, inflammatory and monoaminergic systems
Varinder Singh, Richa Shri, Parul Sood, Manjinder Singh, Thakur Gurjeet Singh, Ravinder Singh, Amarjot Kaur, Amit Kumar, Tanveer Singh, Sheikh F. Ahmad, Sabry M. Attia
Abstract
• HTMF mitigated lead-induced neurotoxicity in rats. • HTMF improved memory and motor functions in rats. • HTMF showed chelating effects. • HTMF modulated brain oxidative stress, inflammation and monoaminergic system. Lead (Pb) is known to cause neurological changes, but antioxidants, chelators, and anti-inflammatory agents mitigates Pb toxicity. Previously, we reported antioxidant and anti-inflammatory effects of 3-hydroxy-3′,4′,5′-trimethoxyflavone (HTMF) derived from Ocimum basilicum L. leaves. This research investigates the neuroprotective properties of HTMF against Pb induced neurotoxicity in rats. Rats were orally administered lead acetate (100 mg/kg) daily for 30 days to induce neurotoxicity, then treated with HTMF (5 and 10 mg/kg) 30 min after Pb exposure. Cognitive and motor functions and brain biochemical parameters were determined to understand HTMF’s mechanism of action. Pb exposure impaired cognition and motor skills, elevated Pb levels, TBARS, TNF-α, IL-6 and MAO A & B, and reduced GSH levels in the brain. HTMF treatment significantly improved memory, motor deficits, and metabolic abnormalities induced by Pb, attributed to its chelating, antioxidative, anti-inflammatory, and monoaminergic modulating properties, suggesting its potential as a therapeutic agent for metal-induced brain injuries.