Necrostatin‐1 protects against reactive oxygen species (ROS)‐induced hepatotoxicity in acetaminophen‐induced acute liver failure

Takemoto, Kenji; Hatano, Etsuro; Iwaisako, Keiko; Takeiri, Masatoshi; Noma, Naruto; Ohmae, Saori; Toriguchi, Kan; Tanabe, Katsuaki; Tanaka, Hirokazu; Seo, Satoru; Taura, Kojiro; Machida, Keigo; Takeda, Norihiko; Saji, Shigehira; Üemoto, Shinji; Asagiri, Masataka

doi:10.1016/j.fob.2014.08.007

Cited by 132 publications

(106 citation statements)

References 44 publications

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“…(2) This would also explain the similarity between the findings from Dara et al and previous results using the chemical inhibitor Nec-1 in the acetaminophen model. (5) Taken together, hepatocytic RIPK1 does neither directly mediate nor indirectly modulate acute toxicity of acetaminophen in mice.…”

Section: Lpc-komentioning

confidence: 97%

Receptor interacting protein kinase 1 (RIPK1) in hepatocytes does not mediate murine acetaminophen toxicity

et al. 2015

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We read with great interest the correspondence from Sachar and Ma and appreciate their pointing out the important issues regarding cholestasis. As suggested, cholestasis could be one of the main causes of hepatic disorders in patients with erythropoietic protoporphyria.(1,2) Indeed, the liver biopsy from the older brother also showed protoporphyrin (PP) deposition in the bile system. However, PP was predominantly observed in the hepatocytes with hepatocyte swelling and necrosis accompanied. Therefore, based on the histological findings and immunohistochemistry, we concluded that the liver damage should be mainly attributed to hepatocyte necrosis, primarily caused by PP deposition in the hepatocytes. Although an increase of the alkaline phosphatase level reflects cholestasis, elevated total bilirubin may reflect damage to hepatocytes as well as cholestasis. On the contrary, the liver biopsy from the younger brother, who had not suffered from liver dysfunction, showed more PP in the biliary system than the liver from the older brother but no PP in the hepatocytes. This evidence also supports the idea that PP deposition in hepatocytes is unique to liver damage, at least in the presented cases, and that the expression of ABCG2, a PP efflux transporter, should be involved in the pathogenesis. For PP detection in pathological specimens, we applied a polarized light microscope; a Maltese cross was confirmed during the observation, indicating that PP deposits were present in hepatocytes.The author also argued that down-regulation of ABCG2 might be a consequence of liver injury because severe inflammation could affect the expression of proteins. We also addressed this issue; we analyzed the expression of other membrane transporters, ABCG6 and PEPT1. We did not find any differences in the expression of these transporters between the two brothers. Therefore, the difference in ABCG2 expression is specific among transporters; it is conceivable that the reduction of ABCG2 is not a result of liver injury. We already discussed this issue in a previous reply. (3) Concerning age as a risk factor for liver damage, both brothers reported in our study were young, showing only a 2-year difference in age. In addition, the older brother had developed hepatic disorders when he was 16 years old, suggesting that the difference in age should not primarily affect the pathogenesis of the cases.

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Section: Lpc-komentioning

confidence: 97%

Receptor interacting protein kinase 1 (RIPK1) in hepatocytes does not mediate murine acetaminophen toxicity

et al. 2015

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“…Although ROS are formed as a natural byproduct of the normal metabolism of oxygen, and have important roles in cell signaling and homeostasis in biological conditions, excessive ROS are detrimental. Various studies have demonstrated that excessive ROS promotes necroptosis in various cell types, whereas inhibiting ROS production reduces necroptosis (13)(14)(15)(16). In addition, previous studies revealed that ROS production is augmented in AKI, and that ROS lead to renal tubular epithelium injury via inflammasome activation, mitochondrion damage and tubular epithelium apoptosis (22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

“…Reactive oxygen species (ROS) promote necroptosis in cardiomyocytes, liver cells, Jurkat cells and lung adenoma cells (13)(14)(15)(16). However, the effect of ROS on the necroptosis of renal tubular epithelium remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have identified necroptosis in ATN induced by various stimuli, including ischemia/reperfusion, contrast medium and cisplatin (10-12). RIP-1 inhibition by necrostatin-1 (Nec-1), or knockout of RIP-3 or MLKL all prevent ATN (10-12).Reactive oxygen species (ROS) promote necroptosis in cardiomyocytes, liver cells, Jurkat cells and lung adenoma cells (13)(14)(15)(16). However, the effect of ROS on the necroptosis of renal tubular epithelium remains unknown.…”

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confidence: 99%

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NADPH oxidase inhibitor, diphenyleneiodonium prevents necroptosis in HK-2 cells

Dong

Chen

et al. 2017

Biomedical Reports

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Abstract. The aim of the present study was to investigate the protective effect of the NADPH oxidase inhibitor, diphenyleneiodonium (DPI) against necroptosis in renal tubular epithelial cells. A necroptosis model of HK-2 cells was established using tumor necrosis factor-α, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone and antimycin A (collectively termed TZA), as in our previous research. The necroptosis inhibitor, necrostatin-1 (Nec-1) or the NADPH oxidase inhibitor, DPI were administered to the necroptosis model. Production of reactive oxygen species (ROS) was detected by dichlorodihydrofluorescein diacetate in the different groups, and the manner of cell death was identified by flow cytometry. Western blot analysis was used to determine the levels of phosphorylation of receptor-interacting protein kinase 3 (RIP-3) and mixed lineage kinase domain-like (MLKL), which are essential to necroptosis. The results revealed that TZA increased the percentages of propidium iodide-positive HK-2 cells from 1.22±0.69 to 8.98±0.73% (P<0.001), and augmented the phosphorylation of RIP-3 and MLKL. ROS levels were increased in the TZA group compared with the control group (27.74±1. IntroductionAcute kidney injury (AKI) is a common clinical syndrome that is characterized by the rapid loss of kidney function and abrupt kidney damage. It is associated with high morbidity and mortality worldwide (1). Acute tubular necrosis (ATN) is the most common and severe pathological manifestation of AKI. Although necrosis has long been considered to be unregulated, previous studies have revealed various types of regulated necrosis that are independent of caspase activities (2). Necroptosis is an important type of regulated necrosis and is involved in various pathological conditions (3-7). Receptor-interacting protein kinase (RIP)-1 receives signals from various death stimuli, and subsequently recruits RIP-3 via RIP homotypic interaction motif domain-mediated interactions and promotes RIP-3 phosphorylation (8,9). Phosphorylated RIP-3 mediates the phosphorylation of mixed-lineage kinase domain-like (MLKL), ultimately leading to rupture of the plasma membrane (7). Previous studies have identified necroptosis in ATN induced by various stimuli, including ischemia/reperfusion, contrast medium and cisplatin (10-12). RIP-1 inhibition by necrostatin-1 (Nec-1), or knockout of RIP-3 or MLKL all prevent ATN (10-12).Reactive oxygen species (ROS) promote necroptosis in cardiomyocytes, liver cells, Jurkat cells and lung adenoma cells (13)(14)(15)(16). However, the effect of ROS on the necroptosis of renal tubular epithelium remains unknown. The present study hypothesized that excessive ROS production may promote necroptosis in HK-2 human kidney cells. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, has been demonstrated to reduce ROS production and exert a protective role in numerous cell types (17)(18)(19)

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“…This could be linked to the direct interface of the antipsychotic drug with hepatic kupffer cells, thereby slowing down its normal functionality. The continuous deactivation of these cells may trigger irreparable liver failure 4 . The observation was supported by the investigation which reported that hepatomegaly as well as hepatitis inflammation of the liver was obvious in patients chronically exposed to antipsychotic drugs 35 .…”

Section: Discussionmentioning

confidence: 99%

Functional Oil from Black Seed Differentially Inhibits Aldose-reductase and Ectonucleotidase Activities by Up-regulating Cellular Energy in Haloperidol-induced Hepatic Toxicity in Rat Liver

Kehinde

2017

J. Oleo Sci.

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Necrostatin‐1 protects against reactive oxygen species (ROS)‐induced hepatotoxicity in acetaminophen‐induced acute liver failure

Abstract: Graphical abstract

Cited by 132 publications

References 44 publications

Receptor interacting protein kinase 1 (RIPK1) in hepatocytes does not mediate murine acetaminophen toxicity

Receptor interacting protein kinase 1 (RIPK1) in hepatocytes does not mediate murine acetaminophen toxicity

NADPH oxidase inhibitor, diphenyleneiodonium prevents necroptosis in HK-2 cells

Functional Oil from Black Seed Differentially Inhibits Aldose-reductase and Ectonucleotidase Activities by Up-regulating Cellular Energy in Haloperidol-induced Hepatic Toxicity in Rat Liver

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