The Potential of Glucose Treatment to Reduce Reactive Oxygen Species Production and Apoptosis of Inflamed Neural Cells In Vitro

Juin-Hong Cherng, Shu-Jen Chang, Hsin-Da Tsai, Chung-Fang Chun, Gang-Yi Fan, Kenneth Dean Reeves, King Hei Stanley Lam and Yung-Tsan Wu

Biomedicines 2023, 11(7), 1837

Abstract

Neuroinflammation is a key feature in the pathogenesis of entrapment neuropathies. Clinical trial evidence suggests that perineural injection of glucose in water at entrapment sites has therapeutic benefits beyond a mere mechanical effect. We previously demonstrated that 12.5–25 mM glucose restored normal metabolism in human SH-SYFY neuronal cells rendered metabolically inactive from TNF-α exposure, a common initiator of neuroinflammation, and reduced secondary elevation of inflammatory cytokines. In the present study, we measured the effects of glucose treatment on cell survival, ROS activity, gene-related inflammation, and cell cycle regulation in the presence of neurogenic inflammation. We exposed SH-SY5Y cells to 10 ng/mL of TNF-α for 24 h to generate an inflammatory environment, followed by 24 h of exposure to 3.125, 6.25, 12.5, and 25 mM glucose. Glucose exposure, particularly at 12.5 mM, preserved apoptotic SH-SY5Y cell survival following a neuroinflammatory insult. ROS production was substantially reduced, suggesting a ROS scavenging effect. Glucose treatment significantly increased levels of CREB, JNK, and p70S6K (p < 0.01), pointing to antioxidative and anti-inflammatory actions through components of the MAPK family and Akt pathways but appeared underpowered (n = 6) to reach significance for NF-κB, p38, ERK1/2, Akt, and STAT5 (p < 0.05). Cell regulation analysis indicated that glucose treatment recovered/restored function in cells arrested in the S or G2/M-phases. In summary, glucose exposure in vitro restores function in apoptotic nerves after TNF-α exposure via several mechanisms, including ROS scavenging and enhancement of MAPK family and Akt pathways. These findings suggest that glucose injection about entrapped peripheral nerves may have several favorable biochemical actions that enhance neuronal cell function.

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