Track topics on Twitter Track topics that are important to you
Liver disease is responsible for more than 42,000 deaths yearly. Elevated hepatic iron levels have been shown to play a role in chronic liver diseases including hereditary hemochromatosis, thalassemia and chronic hepatitis C, while acetaminophen (APAP) is the leading cause of acute liver failure. The goal of this study was to determine whether increased hepatic iron affects APAP induced cytotoxicity, reactive oxygen species (ROS) production and/or mitochondrial dysfunction in primary mouse hepatocytes (PMH) that are differentiated and have gap junction intracellular integrity, properties associated with hepatocytes in vivo and important for conducting toxicant studies. Treatment of PMH with the iron donor 3,5,5-trimethyl-hexanoyl ferrocene (TMHF) caused an elevation in ferritin, reduction in transferrin receptor 1, and accumulation of hemosiderin, but TMHF treatment alone did not induce ROS or cause mitochondrial dysfunction. The threshold APAP dose that induced PMH cell death after TMHF treatment of PMH was lower than in the absence of TMHF. In addition, treatment with the iron chelator desferoxamine (DFO) protected from APAP and resulted in a higher threshold dose being needed to induce cell death. We also showed that after TMHF treatment, APAP induced ROS and mitochondrial dysfunction at earlier time points than treatment with APAP alone; treatment with DFO increased the length of time required for APAP to induce ROS and mitochondrial dysfunction; and treatment with DFO, subsequent to TMHF, partially protected against TMHF potentiated APAP injury. We conclude that iron potentiates the effects of APAP on cytotoxicity, ROS production, and mitochondrial dysfunction in PMH.
Department of Microbiology and Immunology.
This article was published in the following journal.
Name: Toxicological sciences : an official journal of the Society of Toxicology
NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hep...
Coenzyme Q10, (CoQ10) an electron transporter and an antioxidant, protects a variety of cell types against oxidative stress and apoptosis. However, protective effect of CoQ10 on oxidative stress-induc...
Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerat...
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized clinically by cognitive decline and memory loss. The pathological features are amyloid-β peptide (Aβ) plaques and in...
The aim of the present study was to investigate the efficacy of acetyl-l-carnitine (ALCAR) on pathologic changes of mitochondrial respiratory chain activity, ATP production, oxidative stress, and cell...
In Amyotrophic Lateral Sclerosis (ALS), malnutrition is frequent (16 to 50 % of the patients) and is an independent prognostic factor. One of the implicated factors is the increase of rest...
Certain percentage of MDS patients develop iron overload. Iron is known to participate in intracellular reactions that generate free radicals, inducing oxidative stress and apoptosis, whic...
In hemodialysis patient (HD) a reduction of the skeletal muscle mass and strength has previously been reported. This muscle impairment constitutes an independent prognosis factor in HD pat...
High inspiratory oxygen fractions are known to induce oxidative stress and lipid peroxidation. The degrading products of oxidative stress induced lipid peroxidation are in part volatile an...
The purpose of the study is to examine whether Klacid® (Clarithromycin) will induce oxidative stress (stress from oxygen) in healthy subjects. This is done by measuring the content of a p...
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
A ubiquitous stress-responsive enzyme that catalyzes the oxidative cleavage of HEME to yield IRON; CARBON MONOXIDE; and BILIVERDIN.
A naturally occurring phenolic acid which is a carcinogenic inhibitor. It has also been shown to prevent paraquat-induced oxidative stress in rats. (From J Chromatogr A 1996;741(2):223-31; Biosci Biotechnol Biochem 1996;60(5):765-68).
Toxic substances isolated from various strains of Streptomyces. They are 20-membered macrolides that inhibit oxidative phosphorylation and mitochondrial ATPases. Venturicidins A and B are glycosides. Used mainly as tools in the study of mitochondrial function.
Iron or iron compounds used in foods or as food. Dietary iron is important in oxygen transport and the synthesis of the iron-porphyrin proteins hemoglobin, myoglobin, cytochromes, and cytochrome oxidase. Insufficient amounts of dietary iron can lead to iron-deficiency anemia.
Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...
Benign Prostatic Hyperplasia (BPH) Erectile Dysfunction Urology Urology is the branch of medicine concerned with the urinary tract and diseases that affect it. Examples include urethritis, urethrostenosis and incontinence. Urology is a su...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...