Resveratrol prevents protein nitration and release of endonucleases from mitochondria during acetaminophen hepatotoxicity

Du, Kuo; McGill, Mitchell R.; Xie, Yuchao; Bajt, Mary Lynn; Jaeschke, Hartmut

doi:10.1016/j.fct.2015.04.014

Cited by 53 publications

(39 citation statements)

References 72 publications

(108 reference statements)

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“…Metabolism of APAP to its reactive metabolite by Cyp2e1, subsequent APAP-protein binding, and initiation of necrosis signaling are critical to induction of AILI [41]. Interference with these early events affect the severity of hepatotoxicity, especially when a compound or its vehicle is administered simultaneously with, or before APAP [41].…”

Section: Discussionmentioning

confidence: 99%

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice

Jadeja

Urrunaga

Dash

et al. 2015

Biochemical Pharmacology

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Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study to assess the therapeutic potential of WA in a mouse model that mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac (5–6 wk. old) male mice received 200 mg/kg APAP intraperitoneally (i.p.). After 1 h mice were treated with 40 mg/kg WA or vehicle i.p., and euthanized 4 and 16 h later; their livers were harvested and serum collected for analysis. At 4 h, compared to vehicle-treated mice, WA-treated mice had reduced serum ALT levels, hepatocyte necrosis and intrahepatic hemorrhage. All APAP-treated mice had reduced hepatic glutathione (GSH) levels however, reduction in GSH was lower in WA-treated when compared to vehicle-treated mice. Compared to vehicle-treated mice, livers from WA-treated mice had reduced APAP-induced JNK activation, mitochondrial Bax translocation, and nitrotyrosine generation. Compared to vehicle-treated mice, WA-treated mice had increased hepatic up-regulation of Nrf2, Gclc and Nqo1, and down-regulation of Il-6 and Il-1β. The hepatoprotective effect of WA persisted at 16 h. Compared to vehicle-treated mice, WA-treated mice had reduced hepatocyte necrosis and hepatic expression of Il-6, Tnf-α and Il-1β, increased hepatic Gclc and Nqo1 expression and GSH levels, and reduced lipid peroxidation. Finally, in AML12 hepatocytes, WA reduced H2O2-induced oxidative stress and necrosis by preventing GSH depletion. Collectively, these data show mechanisms whereby WA reduces necrotic hepatocyte injury, and demonstrate that WA has therapeutic potential in AILI.

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Section: Discussionmentioning

confidence: 99%

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice

Jadeja

Urrunaga

Dash

et al. 2015

Biochemical Pharmacology

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“…Berries, nuts, grapes RSV decreased protein nitration after APAP treatment, possibly through direct scavenging of peroxynitrite. RSV also inhibited release of apoptosis-inducing factor and endonuclease G from mitochondria independent of Bax pore formation and prevented the downstream nuclear DNA fragmentation Du et al (2015) Aloe vera Aloe vera The mean level of ALT, hepatic MDA, the number of IL-12 and IL-18 positive-stained cells, and hepatic GSH in Aloe vera-treated group were improved as compared with APAP group. Moreover, in the APAP group, the liver showed extensive hemorrhagic hepatic necrosis at all zones while in Aloe vera-treated group, the liver architecture was improved histopathology Werawatganon et al (2014) Apigenin Parsley, onions, oranges, tea, and chamomile…”

Section: Funding Informationmentioning

confidence: 95%

“…The mechanisms that may explain this protection include antioxidant effects, up-regulation of phase II enzymes, modulation of inflammatory responses and induction of mitochondrial biogenesis (Baur et al 2006;Sener et al 2006;Lagouge et al 2006;Masubuchi et al 2009;Bishayee et al 2010). Du et al (2015) administered male mice with APAP (300 mg/kg) and 1.5 h later with RSV (50 mg/kg). RSV reduced liver injury after APAP overdose in mice.…”

Section: Resveratrolmentioning

confidence: 99%

Role of food-derived antioxidant agents against acetaminophen-induced hepatotoxicity

Eugenio‐Pérez

Oca-Solano

Pedraza‐Chaverrí

2016

Pharmaceutical Biology

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Context Acetaminophen (APAP), also known as paracetamol and N-acetyl p-aminophenol, is one of the most frequently used drugs for analgesic and antipyretic purposes on a worldwide basis. It is safe and effective at recommended doses but has the potential for causing hepatotoxicity and acute liver failure (ALF) with overdose. To solve this problem, different strategies have been developed, including the use of compounds isolated from food, which have been studied to characterize their efficacy as natural dietary antioxidants. Objective The objective of this study is to show the beneficial effects of a variety of natural compounds and their use against acetaminophen-induced hepatotoxicity. Methods PubMed database was reviewed to compile data about natural compounds with hepatoprotective effects against APAP toxicity. Results and conclusion As a result, the health-promoting properties of 13 different food-derived compounds with protective effect against APAP-induced hepatotoxicity were described as well as the mechanisms involved in hepatoprotection.ARTICLE HISTORY

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“…Though not yet confirmed in a stroke model, resveratrol scavenges ONOO - and inhibits protein nitration in several other models [139,140,141]. Moreover, liquid chromatography with tandem electrospray mass spectrometry showed that resveratrol is a substrate of ONOO - .…”

Section: Active Compounds From Chinese Herbal Medicine For Targeting mentioning

confidence: 99%

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

Chen¹,

Guan²,

Shen³

2016

Integr Med Int

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Stroke is the leading cause of death and disability worldwide, and ischemic stroke accounts for more than 85% of the stroke incidence. Tissue plasminogen activator (t-PA) is the only FDA-approved drug for ischemic stroke treatment with a narrow treatment time window of 4.5 h. Hemorrhagic transformation (HT) is a severe complication of delayed t-PA treatment in ischemic stroke. Thus, it is critically important to develop combination therapies to reduce HT and extend the therapeutic time window of t-PA. Current progress suggests that peroxynitrite (ONOO^-)/high-mobility group box 1 protein (HMGB1)/matrix metalloproteinase-9 (MMP-9) signaling cascades could be important for attenuating HT during thrombolytic treatment for acute ischemic stroke. Recently, important progress has been made in seeking for natural compounds from Chinese medicine for reducing ischemic stroke injury, with some of them targeting ONOO^-/HMGB1/MMP-9 signaling cascades. Herein, we analyze the roles and interactions of these three targets in mediating HT; subsequently, we summarize the potential compounds from Chinese herbal medicine for attenuating HT and analyze the related targets. Finally, we raise the potential issues to be addressed in further development of these compounds as combination therapy.

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Resveratrol prevents protein nitration and release of endonucleases from mitochondria during acetaminophen hepatotoxicity

Cited by 53 publications

References 72 publications

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice

Role of food-derived antioxidant agents against acetaminophen-induced hepatotoxicity

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

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