Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity

Patients that survive hemorrhage and resuscitation (H/R) may develop a systemic inflammatory response syndrome (SIRS) that leads to dysfunction of vital organs (multiple organ dysfunction syndrome, MODS). SIRS and MODS may involve mitochondrial dysfunction. Under pentobarbital anesthesia, C57BL6 mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer’s solution containing minocycline, tetracycline (both 10 mg/kg body weight) or vehicle. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R with vehicle or tetracycline, ALT increased to 4538 U/L and 3999 U/L, respectively, which minocycline decreased to 1763 U/L (P<0.01). Necrosis and TUNEL also decreased from 24.5% and 17.7 cells/field, respectively, after vehicle to 8.3% and 8.7 cells/field after minocycline. Tetracycline failed to decrease necrosis (23.3%) but decreased apoptosis to 9 cells/field (P<0.05). Minocycline and tetracycline also decreased caspase-3 activity in liver homogenates. Minocycline but not tetracycline decreased lipid peroxidation after resuscitation by 70% (P<0.05). Intravital microscopy showed that minocycline preserved mitochondrial polarization after H/R (P<0.05). In conclusion, minocycline decreases liver injury and oxidative stress after H/R by preventing mitochondrial dysfunction.

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Liver injury in acute fatty liver of pregnancy: Possible link to placental mitochondrial dysfunction and oxidative stress

Hepatology ◽

10.1002/hep.23245 ◽

2009 ◽

Vol 51 (1) ◽

pp. 191-200 ◽

Cited By ~ 45

Author(s):

Sathish Kumar Natarajan ◽

Kavitha R. Thangaraj ◽

C. E. Eapen ◽

Anup Ramachandran ◽

Ashis Mukhopadhya ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Fatty Liver ◽

Mitochondrial Dysfunction ◽

Acute Fatty Liver ◽

And Oxidative Stress

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Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes

PLoS ONE ◽

10.1371/journal.pone.0239625 ◽

2020 ◽

Vol 15 (9) ◽

pp. e0239625

Author(s):

Prasanna M. Chandramouleeswaran ◽

Manti Guha ◽

Masataka Shimonosono ◽

Kelly A. Whelan ◽

Hisatsugu Maekawa ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

And Oxidative Stress

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One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22115851 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5851

Author(s):

Takehito Sugasawa ◽

Seiko Ono ◽

Masato Yonamine ◽

Shin-ichiro Fujita ◽

Yuki Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Early Stage ◽

Droplet Deposition ◽

Nonalcoholic Fatty Liver ◽

Stress Markers ◽

Mitochondrial Dna Copy Number ◽

Short Period ◽

And Oxidative Stress

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.

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Aclonifen causes developmental abnormalities in zebrafish embryos through mitochondrial dysfunction and oxidative stress

The Science of The Total Environment ◽

10.1016/j.scitotenv.2021.145445 ◽

2021 ◽

Vol 771 ◽

pp. 145445

Author(s):

Jin-Young Lee ◽

Hahyun Park ◽

Whasun Lim ◽

Gwonhwa Song

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Zebrafish Embryos ◽

Developmental Abnormalities ◽

And Oxidative Stress

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Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽

10.3390/antiox10020229 ◽

2021 ◽

Vol 10 (2) ◽

pp. 229

Author(s):

JunHyuk Woo ◽

Hyesun Cho ◽

YunHee Seol ◽

Soon Ho Kim ◽

Chanhyeok Park ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Computational Models ◽

Neuronal Damage ◽

Living Organism ◽

The Body ◽

Mitochondrial Functions ◽

A Cell ◽

The Brain ◽

And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

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Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2017.00182 ◽

2017 ◽

Vol 10 ◽

Cited By ~ 27

Author(s):

Geetha A. Shetty ◽

Bharathi Hattiangady ◽

Dinesh Upadhya ◽

Adrian Bates ◽

Sahithi Attaluri ◽

...

Keyword(s):

Oxidative Stress ◽

Animal Model ◽

Mitochondrial Dysfunction ◽

Systemic Inflammation ◽

Gulf War ◽

Gulf War Illness ◽

Chronic Oxidative Stress ◽

Nrf2 Activation ◽

And Oxidative Stress

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trans,trans-2,4-decadienal induces mitochondrial dysfunction and oxidative stress

Journal of Bioenergetics and Biomembranes ◽

10.1007/s10863-008-9137-y ◽

2008 ◽

Vol 40 (2) ◽

pp. 103-109 ◽

Cited By ~ 4

Author(s):

Carlos A. O. Sigolo ◽

Paolo Di Mascio ◽

Alicia J. Kowaltowski ◽

Camila C. M. Garcia ◽

Marisa H. G. Medeiros

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

And Oxidative Stress

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Abstract P074: Mitochondrial Isolevuglandins Contribute To Vascular Oxidative Stress And Mitochondria-targeted Scavenger Of Isolevuglandins Reduces Mitochondrial Dysfunction And Hypertension

Hypertension ◽

10.1161/hyp.76.suppl_1.p074 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Anna Dikalova ◽

Vladimir Mayorov ◽

Liang Xiao ◽

Alexander Panov ◽

Venkataraman Amarnath ◽

...

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Mitochondrial Dysfunction ◽

Vascular Function ◽

Therapeutic Potential ◽

Protein Adducts ◽

Specific Marker ◽

Mitochondrial Oxidative Stress ◽

Major Health Problem ◽

Multiple Drugs

Hypertension remains a major health problem in Western Societies, and blood pressure is poorly controlled in a third of patients despite use of multiple drugs. Mitochondrial dysfunction contributes to hypertension and mitochondria-targeted agents can potentially improve treatment of hypertension. We have proposed that mitochondrial oxidative stress produces reactive dicarbonyl lipid peroxidation products isolevuglandins (isoLGs) and that scavenging of mitochondrial isoLG improves vascular function and reduces hypertension. To test this hypothesis, we have studied the accumulation of mitochondrial isoLG-protein adducts in human patients with essential hypertension and angiotensin II mouse model of hypertension using mass spectrometry and Western blot analysis. The therapeutic potential of targeting mitochondrial isoLG was tested by the novel mitochondria-targeted isoLG scavenger, mito2HOBA. Mitochondrial isoLG in arterioles isolated from hypertensive patients were 250% greater than in arterioles from normotensive subjects, and ex vivo mito2HOBA treatment of arterioles from hypertensive subjects improved deacetylation of a key mitochondrial antioxidant, superoxide dismutase 2 (SOD2). In human aortic endothelial cells, mito2HOBA diminished mitochondrial superoxide and inhibited cardiolipin oxidation, a specific marker of mitochondrial oxidative stress. In angiotensin II-infused mice, mito2HOBA prevented accumulation of mitochondrial isoLG-protein adducts, improved Sirt3 mitochondrial deacetylase activity, reduced vascular superoxide, increased endothelial nitric oxide, improved endothelium-dependent relaxation, and attenuated hypertension. Mito2HOBA preserved mitochondrial respiration, protected ATP production, and reduced mitochondrial permeability pore opening in angiotensin II-infused mice. These data support the role of mitochondrial isoLGs in endothelial dysfunction and hypertension. We conclude that scavenging of mitochondrial isoLGs may have therapeutic potential in treatment of vascular dysfunction and hypertension.

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