Induction of the nuclear factor HIF-1α in acetaminophen toxicity: Evidence for oxidative stress

James, Laura P.; Donahower, Brian; Burke, Angela S.; McCullough, Sandra; Hinson, Jack

doi:10.1016/j.bbrc.2006.02.143

Cited by 33 publications

(39 citation statements)

References 26 publications

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“…This transcription factor activates the expression of genes that are needed to maintain cellular homeostasis in the hypoxic state (Semenza et al 2002). However, previous work postulated that induction of HIF-1α in vivo is secondary to oxidative stress and inflammatory cytokines (Haddad & Harb 2001;James et al 2006) and its overexpression induces the expression of fibrogenic cytokines and collagen III in renal epithelial cell which play an important role in the pathogenesis of tubulointerstitial fibrosis (Basu et al 2011). Administration of carnosine and/or arginine to hypoxic rats , significantly reduced the serum HIF-1α level compared with the hypoxic untreated group.…”

Section: Discussionmentioning

confidence: 99%

Regulating Effect Of Carnosine And /Or L- Arginine On The Expression Of Inflammatory Molecules Induced Nephropathy In The Hypoxic Rat Model

Al-Rasheed

Fadda

Mohamed

et al. 2016

Braz. arch. biol. technol.

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This study aimed to explore the effective role of carnosine and /or L-arginine pro-inflammatory molecules, including tumor necrosis factor-α (TNF-α) , Creactive protein (CRP), vascular endothelial growth factor (VEGF) and heat shock protein -70 (HSP-70) as well as interleukin-6 (IL-6) in renal tissue compared to NaNO2 hypoxic rats . Also, the two agents successfully down modulated the alteration in the serum hypoxia inducible factor 1α (HIF 1α

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Section: Discussionmentioning

confidence: 99%

Regulating Effect Of Carnosine And /Or L- Arginine On The Expression Of Inflammatory Molecules Induced Nephropathy In The Hypoxic Rat Model

Al-Rasheed

Fadda

Mohamed

et al. 2016

Braz. arch. biol. technol.

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“…32 APAP treatment induces oxidative stress evident both in liver tissue and plasma. 33,34 Thus, APAP exposure might increase PCA without an accompanying increase in TF protein.…”

Section: Discussionmentioning

confidence: 99%

Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice

et al. 2007

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Acetaminophen (N-acetyl-p-aminophenol [APAP]) is one of the leading causes of acute liver failure, and APAP hepatotoxicity is associated with coagulopathy in humans. We tested the hypothesis that activation of the coagulation system and downstream protease-activated receptor (PAR)-1 signaling contribute to APAP-induced liver injury. Fasted C57BL/J6 mice were treated with either saline or APAP (400 mg/kg intraperitoneally) and were euthanized 0.5-24 hours later. Hepatotoxicity and coagulation system activation occurred by 2 hours after administration of APAP. Treatment with APAP also caused a rapid and transient increase in liver procoagulant activity. In addition, significant deposition of fibrin was observed in the liver by 2 hours, and the concentration of plasminogen activator inhibitor-1 in plasma increased between 2 and 6 hours. Pretreatment with heparin attenuated the APAP-induced activation of the coagulation system and hepatocellular injury and diminished hepatic fibrin deposition at 6 hours. Loss of hepatocellular glutathione was similar in APAP-treated mice pretreated with saline or heparin, suggesting that heparin did not diminish bioactivation of APAP. In mice deficient in tissue factor, the principal cellular activator of coagulation, APAP-induced liver injury, activation of coagulation, and hepatic fibrin deposition were reduced at 6 hours. A cetaminophen (N-acetyl-p-aminophenol [APAP]) is the leading cause of drug-induced hepatic failure in humans. Early results in animal models revealed that APAP is bioactivated to a reactive metabolite that is responsible for the hepatotoxicity. 1,2 Many subsequent studies have identified numerous factors that appear to contribute to APAP-induced liver injury, including mitochondrial alterations, reactive oxygen and nitrogen species, and cytokines such as tumor necrosis factor-␣. [3][4][5][6][7][8] Despite extensive study, the factors and mechanisms involved in the initiation and progression of hepatocellular lesions during APAP hepatotoxicity are not fully understood.Disturbances in the hemostatic system are well documented in human patients with APAP hepatotoxicity. During hemostasis, formation and lysis of clots is regulated by the balance among coagulant, anticoagulant and fibrinolytic pathways. 9 The coagulation system is activated by tissue factor (TF), and this culminates in the generation of thrombin and formation of insoluble fibrin clots. Dissolution of fibrin clots is mediated by plasmin and is inhibited by plasminogen activator inhibitor-1 (PAI-1). In people who develop APAP-induced liver injury, prothrombin time increases, and this change correlates with the severity of toxicity. [10][11][12] Moreover, the concentrations of several coagulation factors are decreased in APAP-poisoned patients, 13 an effect that could be interpreted to be a consequence of decreased production of coagulation factors by the injured liver. An alternative interpretation, however, is that the decrease in coagula-

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“…However, contradicting evidence exists, indicating that ROS might trigger HIF in the absence of hypoxia. Th is has been suggested by studying liver tissue in acetaminophen-induced liver injury, before the development of overt liver injury and hypoxia [56], and in aged well-fed animals [57]. Th e role of HIF stimulation during oxidative stress therefore needs further assessment.…”

Section: Oxidative Stressmentioning

confidence: 99%