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Caffeine Modulates Cadmium-Induced Oxidative Stress, Neuroinflammation, and Cognitive Impairments by Regulating Nrf-2/HO-1 In Vivo and In Vitro

Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea
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J. Clin. Med. 2019, 8(5), 680; https://doi.org/10.3390/jcm8050680
Received: 19 April 2019 / Revised: 10 May 2019 / Accepted: 12 May 2019 / Published: 14 May 2019
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Abstract

Cadmium (Cd), a nonbiodegradable heavy metal and one of the most neurotoxic environmental and industrial pollutants, promotes disturbances in major organs and tissues following both acute and chronic exposure. In this study, we assessed the neuroprotective potential of caffeine (30 mg/kg) against Cd (5 mg/kg)-induced oxidative stress-mediated neuroinflammation, neuronal apoptosis, and cognitive deficits in male C57BL/6N mice in vivo and in HT-22 and BV-2 cell lines in vitro. Interestingly, our findings indicate that caffeine markedly reduced reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and hemeoxygenase-1 (HO-1), which act as endogenous antioxidant regulators. Also, 8-dihydro-8-oxoguanine (8-OXO-G) expression was considerably reduced in the caffeine-treated group as compared to the Cd-treated group. Similarly, caffeine ameliorated Cd-mediated glial activation by reducing the expression of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), and other inflammatory mediators in the cortical and hippocampal regions of the mouse brain. Moreover, caffeine markedly attenuated Cd-induced neuronal loss, synaptic dysfunction, and learning and cognitive deficits. Of note, nuclear factor-2 erythroid-2 (Nrf-2) gene silencing and nuclear factor-κB (NF-κB) inhibition studies revealed that caffeine exerted neuroprotection via regulation of Nrf-2- and NF-κB-dependent mechanisms in the HT-22 and BV-2 cell lines, respectively. On the whole, these findings reveal that caffeine rescues Cd-induced oxidative stress-mediated neuroinflammation, neurodegeneration, and memory impairment. The present study suggests that caffeine might be a potential antioxidant and neuroprotective agent against Cd-induced neurodegeneration. View Full-Text
Keywords: cadmium; caffeine; reactive oxygen species (ROS); Nrf-2/HO-1; memory impairments; p-NF-κB; neurodegeneration cadmium; caffeine; reactive oxygen species (ROS); Nrf-2/HO-1; memory impairments; p-NF-κB; neurodegeneration
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Khan, A.; Ikram, M.; Muhammad, T.; Park, J.; Kim, M.O. Caffeine Modulates Cadmium-Induced Oxidative Stress, Neuroinflammation, and Cognitive Impairments by Regulating Nrf-2/HO-1 In Vivo and In Vitro. J. Clin. Med. 2019, 8, 680.

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