A compound with promising anticancer properties, 3-bromopyruvate (3-BP) is a synthetic derivative of a pyruvate molecule; however, its toxicity in non-malignant cells has not yet been fully elucidated. Therefore, we elected to study the effects of 3-BP on primary hepatocytes in monolayer cultures, permeabilized hepatocytes and isolated mitochondria. After a 1-h treatment with 100 μM 3-BP cell viability of rat hepatocytes was decreased by 30 % as measured by the WST-1 test (p < 0.001); after 3-h exposure to ≥200 μM 3-BP lactate dehydrogenase leakage was increased (p < 0.001). Reactive oxygen species production was increased in the cell cultures after a 1-h treatment at concentrations ≥100 μmol/l (p < 0.01), and caspase 3 activity was increased after a 20-h incubation with 150 μM and 200 μM 3-BP (p < 0.001). This toxic effect of 3-BP was also proved using primary mouse hepatocytes. In isolated mitochondria, 3-BP induced a dose- and time-dependent decrease of mitochondrial membrane potential during a 10-min incubation both with Complex I substrates glutamate + malate or Complex II substrate succinate, although this decrease was more pronounced with the latter. We also measured the effect of 3-BP on respiration of isolated mitochondria. ADP-activated respiration was inhibited by 20 μM 3-BP within 10 min. Similar effects were also found in permeabilized hepatocytes of both species.
IntroductionAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a progressive and rapid course. Fatigue and depression are common among ALS patients. The aim of this study was to determine the relationship between depression and fatigue in Iranian ALS patients.MethodsIn this 2012 cross-sectional study, 40 ALS patients, including 22 females and 18 males, were selected through consecutive relapsing-remitting, and 40 age- and gender-matched health controls (HCs) were recruited from Loghman Hakim Hospital in Tehran, Iran. The Persian version of the Fatigue Severity Scale (FSS-Per) questionnaire and depression substance of Hospital Anxiety and Depression Scale (HADS) were used to assess fatigue and depression. Data were analyzed using the Kolmogorov-Sminov Test, Levene’s test, Independent Samples t-test, and Pearson product-moment correlation coefficient.ResultsWe identified a significant and positive relationship between fatigue and depression in patients with ALS (p=0.000). Furthermore, the scores of fatigue and depression in ALS patients were higher than in non-ALS patients.ConclusionThe results indicated that there was a relationship between fatigue and depression in ALS patients and that early intervention services can improve these symptoms. Further studies are suggested to investigate the direction of such relationship.
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