Exposure of cultured rat hippocampal neurons to glutamate resulted in accumulation of cellular peroxides (measured using the dye 2,7-dichlorofluorescein). Peroxide accumulation was prevented by an N-methyl-D-aspartate (NMDA) receptor antagonist and by removal of extracellular Ca2+, indicating the involvement of NMDA receptor-induced Ca2+ influx in peroxide accumulation. Glutamate-induced reactive oxygen species contributed to loss of Ca2+ homeostasis and excitotoxic injury because antioxidants (vitamin E, propyl gallate, and N-tert-butyl-alpha-phenylnitrone) suppressed glutamate-induced elevation of intracellular Ca2+ concentration ([Ca2+]i) and cell death. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF), but not ciliary neurotrophic factor, each suppressed accumulation of peroxides induced by glutamate and protected neurons against excitotoxicity. bFGF, NGF, and BDNF each increased (to varying degrees) activity levels of superoxide dismutases and glutathione reductase. NGF increased catalase activity, and BDNF increased glutathione peroxidase activity. The ability of the neurotrophic factors to suppress glutamate toxicity and glutamate-induced peroxide accumulation was attenuated by the tyrosine kinase inhibitor genistein, indicating the requirement for tyrosine phosphorylation in the neuro-protective signal transduction mechanism. The data suggest that glutamate toxicity involves peroxide production, which contributes to loss of Ca2+ homeostasis, and that induction of antioxidant defense systems is a mechanism underlying the [Ca2+]i-stabilizing and excitoprotective actions of neurotrophic factors.

Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons.

Protective strategies against ischemic injury of the liver.

Nucleoside and nucleobase transport systems of mammalian cells

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1053/jhep.2000.9323

Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury

Neutrophils are involved in organ damage induced by an excessive acute inflammatory response after ischemia-reperfusion, trauma, and sepsis. In addition to causing vascular injury, neutrophils can transmigrate and attack parenchymal cells. This review summarizes recent advances in our understanding of neutrophil-induced parenchymal cell injury using the liver as an example. Reviewed are the mechanisms of neutrophil sequestration in the hepatic vasculature, transendothelial migration, adherence to hepatic parenchymal cells, and mechanisms of cytotoxicity. Discussed are the involvement of various adhesion molecules in these processes, the role of cytokines and chemokines in the pathophysiology, as well as the effects of proteases and reactive oxygen species released by neutrophils. The emerging understanding of the basic mechanisms of neutrophil-induced organ damage is critical for the development of therapeutic strategies to attenuate excessive acute inflammatory responses without compromising essential host defense mechanisms.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1002/jlb.61.6.647

Mechanisms of neutrophil-induced parenchymal cell injury

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840130328

Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury.

Propyl gallate as a hepatoprotector in vitro and in vivo

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840150317

Jun Wu

Papers

Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury.

Propyl gallate as a hepatoprotector in vitro and in vivo

Enhancement in antioxidant-based hepatoprotective activity of Trolox by its conjugation to lactosylphenylpyranoside.