Endoplasmic reticulum stress response in nonalcoholic fatty liver disease

Ali, Arushana; Zhang, Kezhong

doi:10.4103/ed.ed_11_18

Cited by 1 publication

(1 citation statement)

References 4 publications

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“…Further work conducted by our group and others suggests a role for the endoplasmic reticulum (ER) in mediating both the inflammatory and oxidative mechanisms of cellular injury observed in this study. Specifically, the protein constituents of the ER stress (ERS) signaling pathway have been found to be upregulated in traumatic brain 39 and liver 40 , 41 injury models, while expression of TNF-α and ROS has been found to be decreased when ERS was inhibited 42 . A growing body of evidence suggests that there is extensive cross-talk between the inflammatory response and ERS 43 : several stimuli (lipids, cytokines, or injury) appear to activate ERS, which then further disrupts metabolic functions, causing more inflammation 44 .…”

Section: Discussionmentioning

confidence: 99%

Phenothiazines Enhance the Hypothermic Preservation of Liver Grafts: A Pilot in Vitro Study

Yang

Stone

et al. 2019

Cell Transplant

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In vitro liver conservation is an issue of ongoing critical importance in graft transplantation. In this study, we investigated the possibility of augmenting the standard pre-transplant liver conservation protocol (University of Wisconsin (UW) cold solution) with the phenothiazines chlorpromazine and promethazine. Livers from male Sprague-Dawley rats were preserved either in UW solution alone, or in UW solution plus either 2.4, 3.6, or 4.8 mg chlorpromazine and promethazine (CþP, 1:1). The extent of liver injury following preservation was determined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the ratio of AST/ALT, morphological changes as assessed by hematoxylin-eosin staining, apoptotic cell death as determined by ELISA, and by expression of the apoptotic regulatory proteins BAX and Bcl-2. Levels of glucose (GLU) and lactate dehydrogenase (LDH) in the preservation liquid were determined at 3, 12, and 24 h after incubation to assess glucose metabolism. Oxidative stress was assessed by levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA), and inflammatory cytokine expression was evaluated with Western blotting. CþP augmentation induced significant reductions in ALT and AST activities; the AST/ALT ratio; as well as in cellular swelling, vacuolar degeneration, apoptosis, and BAX expression. These changes were associated with lowered levels of GLU and LDH; decreased expression of SOD, MDA, ROS, TNF-a, and IL-1b; and increased expression of Bcl-2. We conclude that CþP augments hypothermic preservation of liver tissue by protecting hepatocytes from ischemia-induced oxidative stress and metabolic dysfunction. This result provides a basis for improvement of the current preservation strategy, and thus for the development of a more effective graft conservation method.

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