Aluminum, lead and manganese mixture exacerbates oxidative stress, neuroinflammation, and apoptosis via downregulation of Nrf-2/HO-1/BDNF signaling pathway in rats.
Baridoo Donatus Dooka, Chinna N Orish, Anthonet N Ezejiofor, Chidinma P Anyachor, Theresa C Umeji, Kpobari W Nkpaa, Cecilia N Obasi, Ana Cirovic, Aleksandar Cirovic, Orish E Orisakwe
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引用次数: 0
Abstract
Heavy metals have been reported to induce neurotoxicity associated with neurodegenerative disorders. However, there is a dearth of information on Al, Pb, and Mn mixture exposure on cerebral cortex functions. This study is aimed at evaluating the effects of Al, Pb, and Mn mixture on the cerebral cortex functions. Rats were exposed to Pb 20 mg/kg, Al 35mg/kg and Mn 0.564mg/kg body weight singly or in combination for 90 days. Our results showed that Al, Pb and Mn singly or in combination exposure significantly (p ≤ 0.05) decreased antioxidant enzymes activities, glutathione level and increased oxidative stress and neuroinflammation biomarkers in the cerebral cortex of the exposed rats. Moreover, induction of inflammation maker i.e., COX-2 was associated with increases in apoptotic induction. Furthermore, Al, Pb and Mn singling or in combination exposure significantly (p ≤ 0.05) increased Nrf-2 and decreased BDNF and HO-1 induction as well as increased amyloid precursor proteins and decreased occludin level. Taken together, our result indicates that Al, Pb, and Mn mixture exacerbates oxidative stress, neuroinflammation, and apoptosis via downregulation of Nrf2/HO-1/BDNF signaling pathway.
期刊介绍:
The journal Biomarkers brings together all aspects of the rapidly growing field of biomarker research, encompassing their various uses and applications in one essential source.
Biomarkers provides a vital forum for the exchange of ideas and concepts in all areas of biomarker research. High quality papers in four main areas are accepted and manuscripts describing novel biomarkers and their subsequent validation are especially encouraged:
• Biomarkers of disease
• Biomarkers of exposure
• Biomarkers of response
• Biomarkers of susceptibility
Manuscripts can describe biomarkers measured in humans or other animals in vivo or in vitro. Biomarkers will consider publishing negative data from studies of biomarkers of susceptibility in human populations.