Divergent effects of paracetamol on reactive oxygen intermediate and reactive nitrogen intermediate production by U937 cells.

Jamil, I; Symonds, Alistair L. J.; Lynch, Shaina M.; Alalami, O; Smyth, Michael; Martin, Noreen

doi:10.3892/ijmm.4.3.309

Cited by 4 publications

(8 citation statements)

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“…5B). In contrast, caspase-9 and caspase-3 activities were abrogated in mice preventively treated with MnTBAP 10 .…”

Section: In Vivo Effects Of Mntbap On Cytochrome C Release and Caspasementioning

confidence: 88%

“…5A). The leakage of cytochrome c was inhibited by pretreatment with MnTBAP 10 . Under the same conditions, caspase-9 and caspase-3 also were activated in hepatocytes from mice intoxicated with APAP 1000 , as assessed by the cleavage of the respective peptide substrates of those enzymes (Fig.…”

Section: In Vivo Effects Of Mntbap On Cytochrome C Release and Caspasementioning

confidence: 96%

“…1). Preventive treatment of mice with MnTBAP 10, MnTBAP 20 , and MnTBAP 50po administered 2 hours before APAP 1000 increased the survival rates to 65% (P Ͻ .001 vs. nontreated mice), 90% (P Ͻ .001 vs. nontreated mice), and 66.6% (P Ͻ .001 vs. nontreated mice) at 24 hours, respectively (Fig. 1A).…”

Section: Survivalmentioning

confidence: 97%

“…In the experimental group, the animals preventively treated by MnTBAP 10 , as above, received 50 mg/kg of APAP intraperitoneally. Controls received PBS instead of MnT-BAP 10 . APAP and its metabolites in urine were analyzed using the method of Esteban et al, 16 …”

Section: Cytofluorometric Analysis Of Ros Mitochondrial Transmembranmentioning

confidence: 99%

“…However, its inconstant effectiveness may be explained by its lack of effect on highly toxic reactive oxygen species (ROS) possibly generated in hepatocytes as they are in other cell types exposed to APAP. 10 Those radicals are normally detoxified by specific enzymes. Indeed, Cu/Zn-dependent or Mn-dependent superoxide dismutase (SOD) converts superoxide anion (O 2 oϪ ) into hydrogen peroxide (H 2 O 2 ), which is detoxified by catalase, glutathione peroxidase (Gpx), and thioredoxin.…”

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confidence: 99%

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Detoxification of Reactive Oxygen Species by A Nonpeptidyl Mimic of Superoxide Dismutase Cures Acetaminophen–Induced Acute Liver Failure in the Mouse

Ferret

2001

Hepatology

135

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Drug-induced acute liver failure (ALF) is a devastating and often fatal disease mainly caused by poisoning by acetaminophen (APAP). The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), that leads to gluthatione depletion has been suspected to be the main effector of hepatocyte apoptosis during APAP-induced ALF. We have investigated whether reactive oxygen species (ROS) also play a role in APAP-induced ALF, and whether manganese III tetrakis (5,10,15,20 benzoic acid) (MnTBAP), a mimic of superoxide dismutase (SOD) with catalase-like activity, can treat the disease in mice. The effects of MnTBAP were tested on APAP-intoxicated mice and on isolated hepatocytes incubated with APAP. MnTBAP preventively and curatively administered significantly improved survival times, and dramatically reduced serum transaminase activity levels and parenchymal lesions in APAP-intoxicated mice. Whereas pretreatment with N-acetyl-L-cysteine (NAC) prevented ALF in a dose-dependent manner, the molecule was ineffective when curatively administered. The significant increase in glutathione peroxidase (Gpx) activity following APAP administration, and the beneficial effects of MnTBAP suggested that ROS were produced during APAP-induced ALF. A direct evidence of ROS generation was provided by flow cytometry of isolated hepatocytes incubated with APAP. In vitro, ROS production was associated with mitochondrial damage characterized by the collapse of transmembrane potential and the loss of cardiolipin content. In livers of intoxicated mice, ALF was associated with cytochrome c release that led to the activation of caspases-9 and -3. The capacity of MnTBAP to abrogate all those alterations suggests that ROS play a role in APAP-induced apoptosis of hepatocytes, and explains the beneficial effects of MnTBAP, which could be of interest in APAP-induced ALF in humans.

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“…5B). In contrast, caspase-9 and caspase-3 activities were abrogated in mice preventively treated with MnTBAP 10 .…”

Section: In Vivo Effects Of Mntbap On Cytochrome C Release and Caspasementioning

confidence: 88%

Section: In Vivo Effects Of Mntbap On Cytochrome C Release and Caspasementioning

confidence: 96%

Section: Survivalmentioning

confidence: 97%

Section: Cytofluorometric Analysis Of Ros Mitochondrial Transmembranmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Detoxification of Reactive Oxygen Species by A Nonpeptidyl Mimic of Superoxide Dismutase Cures Acetaminophen–Induced Acute Liver Failure in the Mouse

Ferret

2001

Hepatology

135

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3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism

et al. 2018

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Effects of paracetamol on the polychaete Hediste diversicolor: occurrence of oxidative stress, cyclooxygenase inhibition and behavioural alterations

Nogueira

Nunes

2021

Environ Sci Pollut Res

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Divergent effects of paracetamol on reactive oxygen intermediate and reactive nitrogen intermediate production by U937 cells.

Cited by 4 publications

References 0 publications

Detoxification of Reactive Oxygen Species by A Nonpeptidyl Mimic of Superoxide Dismutase Cures Acetaminophen–Induced Acute Liver Failure in the Mouse

Detoxification of Reactive Oxygen Species by A Nonpeptidyl Mimic of Superoxide Dismutase Cures Acetaminophen–Induced Acute Liver Failure in the Mouse

3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism

Effects of paracetamol on the polychaete Hediste diversicolor: occurrence of oxidative stress, cyclooxygenase inhibition and behavioural alterations

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