Acetaminophen hepatotoxicity is the leading cause of drug-induced liver failure. Despite substantial efforts in the past, the mechanisms of acetaminophen-induced liver cell injury are still incompletely understood. Recent advances suggest that reactive metabolite formation, glutathione depletion, and alkylation of proteins, especially mitochondrial proteins, are critical initiating events for t...

In vivo studies have reported conflicting effects of insulin on mixed tissue protein synthesis rates. To test the hypothesis that insulin has differential effects on synthesis rates of various protein fractions in different organs, we infused miniature swine (n = 8 per group) with saline, insulin alone (at 0.7 mU/kg(-1). min(-1)), or insulin plus an amino acid mixture for 8 h. Fractional synthe...

Hepatic mitochondrial function, APOC-III, and LPL are potential targets for triglyceride (TG)-lowering drugs. After 3 weeks of dietary treatment with the compound 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA), the hepatic mitochondrial FA oxidation increased more than 5-fold in male Wistar rats. Gene expression analysis in liver showed significant downregulation of APOC-III and upregulati...

Biochemical and histopathological studies provide evidence of acute mitochondrial insult in Reye’s syndrome. These studies suggest that the metabolic abnormalities seen in Reye’s syndrome could be due to mitochondrial dysfunction (1). In the liver of Reye’s syndrome patients, the activities of all mitochondrial enzymes assayed to date have been decreased, whereas most of the cytoplasmic enzyme ...

Acetaminophen hepatotoxicity is the leading cause of druginduced liver failure. Despite substantial efforts in the past, the mechanisms of acetaminophen-induced liver cell injury are still incompletely understood. Recent advances suggest that reactive metabolite formation, glutathione depletion, and alkylation of proteins, especially mitochondrial proteins, are critical initiating events for th...

Remote organ impairments are frequent and increase patient morbidity and mortality after lower limb ischemia-reperfusion (IR). We challenged the hypothesis that lower limb IR might also impair lung, renal, and liver mitochondrial respiration. Two-hour tourniquet-induced ischemia was performed on both hindlimbs, followed by a two-hour reperfusion period in C57BL6 mice. Lungs, liver and kidneys m...

The biosynthesis of mammalian mitochondrial cytochromes was explored in primary hepatocyte cultures. When these were pulsed with [35S]methionine in the presence of cycloheximide, eight discrete mitochondrial polypeptides were detected by fluorography after their resolution under denaturing conditions by polyacrylamide gel electrophoresis. Since the pulse labeling of the polypeptides was sensiti...

BACKGROUND Recent studies showed a link between a high fat diet (HFD)-induced obesity and lipid accumulation in non-adipose tissues, such as skeletal muscle and liver, and insulin resistance (IR). Although the mechanisms responsible for IR in those tissues are different, oxidative stress and mitochondrial dysfunction have been implicated in the disease process. We tested the hypothesis that HFD...

In a series of 218 patients diagnosed as having primary biliary cirrhosis only nine exhibited a negative serum mitochondrial antibody. On examining additional specimens from these patients, seven were found to be positive, giving a final incidence of greater than 99%. The two patients whose sera remained negative for the mitochondrial antibody had liver histology compatible with the diagnosis o...

The exact cause of liver failure occurring after long standing biliary obstruction is not known. Impairment of hepatic mitochondrial respiration was postulated in some studies. Sodium thiosulphate (STS) is known to have a protective effect on liver function during administration of hepatotoxic chemotherapy. In the present experimental study the effect of treatment with STS in the presence of ob...