Rutin abrogates manganese—Induced striatal and hippocampal toxicity via inhibition of iron depletion, oxidative stress, inflammation and suppressing the NF-κB signaling pathway

Abstract

Excess exposure to Manganese (Mn) promotes oxidative stress and neuro-inflammation. Rutin (RUT) has been found to exhibit both anti-oxidative stress and anti-inflammatory properties. This study aimed to investigate the effects of RUT on Mn accumulation, endogenous iron (Fe) depletion, oxidative stress, inflammation and nuclear factor kappa B (NF-κB) signaling pathways in the hippocampus and striatum of Mn – induced rats. Rats were treated with 30 mg/kg Mn body weight alone or orally co-treated by gavage with RUT at 50 and at 100 mg/kg body weight for 35 consecutive days. Thereafter, we investigated Mn and endogenous Fe levels, acetylcholinesterase activity, oxidative stress markers, pro-inflammatory cytokines and nuclear factor kappa B (NF-κB) in the hippocampus and striatum of rats. The results indicate that Mn induced Mn – accumulation, Fe depletion, oxidative stress, inflammation and the activation of acetylcholinesterase activity and NF-κB signaling pathways in the hippocampus and striatum of the rats. However, RUT attenuated Fe depletion, oxidative stress and inflammation and suppressed acetylcholinesterase activity and NF-κB pathway via downstream regulations of tumor necrosis factor alpha, interleukin I beta and interleukin 6. Taken together, our present study demonstrates that RUT abrogates Mn – induced striatal and hippocampal toxicity via inhibition of Fe depletion, oxidative stress, inflammation and suppressing the NF-κB signaling pathways. Our results indicate that RUT may be of use as a neuroprotective agent against Mn – induced neuronal toxicity.