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Oxidative stress is a critical mediator in liver injury of steatohepatitis. The transcription factor Nrf2 serves as a cellular stress sensor and is a key regulator for induction of hepatic detoxification and antioxidative stress systems. The involvement of Nrf2 in defense against the development of steatohepatitis remains unknown. We aimed to investigate(More)
BACKGROUND The transcription factor nuclear factor-E2-related factor-2 (Nrf2) inhibits lipid accumulation and oxidative stress in the liver by interfering with lipogenic pathways and inducing antioxidative stress genes. METHODS The involvement of Nrf2 in defense against the development of steatohepatitis was studied in an experimental model induced by an(More)
BACKGROUND The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is a key regulator for induction of hepatic antioxidative stress systems. We aimed to investigate whether activation of Nrf2 protects against steatohepatitis. METHOD Wild-type mice (WT), Nrf2 gene-null mice (Nrf2-null) and Keap1 gene-knockdown mice (Keap1-kd), which represent(More)
Preconditioning of sublethal ischemia implies a cytoprotective mechanism against subsequent ischemia—induced cell death; however, the precise mechanism by which preconditioning protects against ischemic injury is not known. In the present study, we clarified whether pretreatment with a sublethal concentration of H2O2 could counter subsequent H2O2-induced(More)
The transcription factor Nrf2 is a key regulator for hepatic induction of detoxifying enzymes, antioxidative stress genes and Mrp efflux transporters. We aimed to investigate whether Nrf2 activation counteracts liver injury associated with cholestasis. The role of Nrf2 activation in counteracting cholestatic liver injury was studied using a bile(More)
BACKGROUND AND PURPOSE Glutamate excitotoxicity may be involved in ischaemic injury to the CNS and some neurodegenerative diseases, such as Alzheimer's disease. Donepezil, an acetylcholinesterase (AChE) inhibitor, exerts neuroprotective effects. Here we demonstrated a novel mechanism underlying the neuroprotection induced by donepezil. EXPERIMENTAL(More)
Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described(More)
BACKGROUND AND PURPOSE Several clinical trials and in vivo animal experiments have suggested that blockade of angiotensin receptor type 1 (AT(1)) improves ischaemic outcomes. However, the mechanism(s) underlying these effects has not been elucidated. Here, we have investigated the protective effects of pretreatment with AT(1) receptor antagonists, losartan(More)
Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various kinds of cells such as insulin-producing beta cells. However, the beneficial effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has been unknown. In this study, we examined the effect of STZ on neurite outgrowth in mouse neuronal Neuro2a cells. STZ (0.01(More)
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