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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #298506

Title: Ischemia-induced endothelial cell swelling and mitochondrial dysfunction are attenuated by dietary polyphenols in vitro

Author
item PANICKAR, KIRAN - University Of Maryland
item QIN, BOLIN - Integrity Neutraceuticals
item Anderson, Richard

Submitted to: Nutritional Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2014
Publication Date: N/A
Citation: N/A

Interpretive Summary: Polyphenols possess anti-oxidant and anti-inflammatory properties. Oxidative stress and inflammation have been implicated in the pathogenesis of strokes. Oxidative stress and inflammations lead to damage of the endothelial cells lining the blood vessels in the brain. Endothelial cell swelling may contribute to a leaky blood-brain barrier which may result in swelling of the brain and ultimately death. We investigated the protective effects of polyphenols on cell swelling in brain cell cultures subjected to 5 hr oxygen-glucose deprivation, a model to mimic strokes. A polyphenol-rich extract from green tea, a polyphenol trimer from cinnamon, and resveratrol, found in grapes, prevented the induced-swelling in brain cells. These results indicate that the polyphenols reduce mitochondrial reactive oxygen species and subsequent cell swelling in endothelial cells following ischemic injury and thus may reduce brain swelling and associated neural damage associated with strokes. These data should be of benefit to scientists, medical personnel, and the lay public.

Technical Abstract: Polyphenols possess anti-oxidant and anti-inflammatory properties. Oxidative stress (OS) and inflammation have been implicated in the pathogenesis of cytotoxic brain edema in cerebral ischemia. In addition, OS and pro-inflammatory cytokines also damage the endothelial cells and the neurovascular unit. Endothelial cell swelling may contribute to a leaky blood-brain barrier which may result in vasogenic edema in the continued presence of the existing cytotoxic edema. We investigated the protective effects of polyphenols on cytotoxic cell swelling in bEND3 endothelial cultures subjected to 5 hr oxygen-glucose deprivation (OGD). A polyphenol-rich extract from green tea (GT), a polyphenol trimer from cinnamon, and resveratrol prevented the OGD-induced rise in mitochondrial free radicals, cell swelling, and the dissipation of the inner mitochondrial membrane potential. Monocyte chemoattractant protein (also called CCL2), a chemokine, but not TNF-a or IL-6, augmented the cell swelling. This effect of MCP-1 was attenuated by the polyphenols. Cyclosporin A, a blocker of the mitochondrial permeability transition pore (mPT), did not attenuate cell swelling but BAPTA-AM, an intracellular calcium chelator did, indicating a role of [Ca2+]i but not the mPT in cell swelling. These results indicate that the polyphenols reduce mitochondrial ROS and subsequent cell swelling in endothelial cells following ischemic injury and thus may reduce brain edema and associated neural damage in ischemia. One possible mechanism by which the polyphenols may attenuate endothelial cell swelling is through the reduction in [Ca2+]i.