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

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.

Rutin attenuates neurobehavioral deficits, oxidative stress, neuro-inflammation and apoptosis in fluoride treated rats.

Studies have shown that high exposure to fluoride (NaF) induces neurotoxicity. Rutin (RUT), a citrus flavonoid, has been reported to have antioxidant, anti-inflammatory and anti-apoptotic properties. The aim of this study was to investigate the neuroprotective mechanism(s) of RUT on NaF - induced neurotoxicity. Rats were exposed to NaF alone in drinking water at 15 mg/L alone ad libitum or orally co-treated by gavage with RUT at 50 and 100 mg/kg body weight for 31 consecutive days. A video-tracking software was used to monitor the motor and locomotive behavior during a 5 - min trial time in a novel environment. Thereafter, acetylcholinesterase (AChE) activity, oxidative stress markers, pro-inflammatory cytokines and caspase - 3 activity were determined in the cerebrum and striatum. The result indicates that NaF - induced neurobehavioral deficits. RUT mediated the reversal of the neurobehavioral deficits and enhanced the exploratory profile of NaF - treated rats as supported by the track plot analyses. Moreover, RUT attenuated the NaF - induced inhibition of antioxidant enzymes and AChE activity and inhibits lipid peroxidation, neuro-inflammation and apoptosis in the cerebrum and striatum of the rats. Collectively, the present study demonstrated that RUT attenuates NaF - Induced toxicity in the cerebrum and striatum of rats via mechanisms involving enhancement of AChE activity, antioxidant status with concomitant inhibition of lipid peroxidation, neuro-inflammation and apoptosis in rats. RUT may be used as a neuroprotective agent against NaF - induced neurotoxicity.