1,721,125 research outputs found
Oxidative Stress, Antioxidant Defenses, and the Liver
No full textOxidative stress is an unavoidable consequence of life in an oxygenrich
atmosphere. Reactive oxygen species (ROS) and reactive
nitrogen species (RNS) are generated as by-products of aerobic
metabolism and are critical intermediates in the normal physiology
and pathophysiology of hepatocytes. To cope with ROS and RNS,
cells have developed antioxidant defenses in order to maintain the
balance between production and detoxification processes. ROS are
important in the creation of oxidative stimuli required for normal
physiologic homeostasis of hepatocytes, but when the equilibrium
between ROS generation and the antioxidant defense of the cell is
disrupted, the consequence is the generation of an oxidative stress
condition. In this chapter we will describe the main cellular source
of free radicals, the damages generated by ROS accumulation, and
all the principal enzymatic and non-enzymatic antioxidant defenses
Abnormal hepatic uptake of low doses of sulfobromophthalein in Gilbert's syndrome: the role of reduced affinity of the plasma membrane carrier of organic anions
No full textBilirubin disrupts calcium homeostasis in neonatal hippocampal neurons: a new pathway of neurotoxicity
Full text linkSevere hyperbilirubinemia leads to bilirubin encephalopathy in neonates, causing irreversible neurological sequelae. We investigated the nature of neuronal selective vulnerability to unconjugated bilirubin (UCB) toxicity. The maintenance of intracellular calcium homeostasis is crucial for neuron survival. Calcium release from endoplasmic reticulum (ER) during ER-stress can lead to apoptosis trough the activation of Caspase-12. By live calcium imaging we monitored the generation of calcium signals in dissociated hippocampal neurons and glial cells exposed to increasing UCB concentrations. We showed the ability of UCB to alter intracellular calcium homeostasis, inducing the appearance of repetitive intracellular calcium oscillations. The contribution of intracellular calcium stores and the induction and activation of proteins involved in the apoptotic calcium-dependent signaling were also assessed. Thapsigargin, a specific inhibitor of Sarco/endoplasmic reticulum ATPase (SERCA) pumps, significantly reduced the duration of Ca2+ oscillation associated with UCB exposure indicating that UCB strongly interfered with the reticulum calcium stores. On the contrary, in pure astrocyte cultures, spontaneous Ca2+ transient duration was not altered by UCB. The protein content of GRP78, AT6, CHOP, Calpain and Caspase-12 of neuronal cells treated with UCB for 24 h was at least twofold higher compared to controls. Calcium-dependent Calpain and Caspase-12 induction by UCB were significantly reduced by 50% and 98%, respectively when cells were pretreated with the ER-stress inhibitor 4-PBA. These results show the strong and direct interference of UCB with neuronal intracellular Ca2+dynamics, suggesting ER Ca2+ stores as a primary target of UCB toxicity with the activation of the apoptotic ER-stress-dependent pathway
Alterations in the redox state and liver damage: Hints from the EASL Basic School of Hepatology
No full textSummary
The importance of a correct balance between oxidative and reductive events has been shown to have a paramount effect on cell function for quite a long time. However, in spite of this body of rapidly growing evidence, the implication of the alteration of the redox state in human disease has been so far much less appreciated. Liver diseases make no exception. Although not fully comprehensive, this article reports what discussed during an EASL Basic School held in 2012 in Trieste, Italy, where the effect of the alteration of the redox state was addressed in different experimental and human models. This translational approach resulted in further stressing the concept that this topic should be expanded in the future not only to better understand how oxidative stress may be linked to a liver damage but also, perhaps more important, how this may be the target for better, more focused treatments. In parallel, understanding how alteration of the redox balance may be associated with liver damage may help define sensitive and ideally early biomarkers of the disorder.
Abbreviations: ROS, reactive oxygen species, RNS, reactive nitrogen species, SOD, superoxide dismutase, ALI, acute liver injuries, CLD, chronic liver diseases, HCC, hepatocarcinoma, HBV, hepatitis B virus, HCV, hepatitis C virus, NAFLD, non-alcoholic fatty liver disease, MDA, malondialdehyde, 4-HNE, 4-hydroxynonenal, APE1/Ref-1, apurinic apyrimidinic endonuclease/redox effector factor 1, TNF, tumor necrosis factor, NOS2, nitric oxide synthase 2, ETC, electron transport chain, I/R, ischemia/reperfusion, FA, fatty acids, NASH, non-alcoholic steatohepatitis, ASH, alcoholic steatohepatitis, 8OHdG, 8-hydrossyguanosine, HIF-1 α, hypoxia-inducible factor 1α, PHD, prolyl-hydroxylases, NF-κB, nuclear factor-κB, GSH, reduced glutathione, GSSG, oxidized glutathione, CVD, cardiovascular disease, ER, endoplasmic reticulum, ERS, endoplasmic reticulum stress, HH, hereditary hemochromatosis, MPO, myeloperoxidase, HLPP, Human Liver Proteome Project, 2-DE, two-dimensional electrophoresis, MS, mass spectrometry, LC, liquid chromatography
Keywords: Liver disease, Oxidative stress, Redox proteomics, Inflammatio
Covid-19 lockdown effect on not institutionalized patients with dementia and caregivers
Full text linkSARS-COV-2 is a severe medical condition. Old patients are very vulnerable, but they have been studied only as institutionalized patients. During the lock-down, little attention is dedicated to old, demented patients who lived at home. This study wants to examine their behavioral reactions by video-phone follow-up. We conducted a longitudinal study in subcortical vascular dementia (sVAD) patients. We enrolled 221 sVAD, not institutionalized patients. We divided sVAD patients into low-medium grade sVAD (A) and severe sVAD (B), based on neuroimaging severity degree and executive alterations. At baseline, at the end of lock-down, and two months later, global behavioral symptoms were recorded for each patient. We found significantly higher scores of general behavioral deterioration, anxiety, delusions, hallucinations and apathy after controlling for sVAD severity. The direct consequence was a drastic increment of psychotropic drugs prescribed and employed during the lock-down. Moreover, caregivers’ stress has been evaluated, together with their anxiety and depression levels. During the lock-down, their scores increased and reflected a severe worsening of their behavior. Our data demonstrate that social isolation induces a severe perception of loneliness and abandonment; these fears can exacerbate behavior disturbances in old-aged frail persons. Thus, these can be considered as indirect victims of SARS-COV-2
Natural history of nonalcoholic steatohepatitis–associated hepatocellular carcinoma
No full textNo abstract availabl
FUNCTIONAL AND IMMUNOLOGIC SIMILARITIES BETWEEN HEPATITIS B VIRUS ENVELOPE PROTEIN AND HUMAN IgA
No full textBilirubin: A promising therapy for Parkinson's disease
Full text linkFollowing the increase in life expectancy, the prevalence of Parkinson’s disease (PD) as the most common movement disorder is expected to rise. Despite the incredibly huge efforts in research to find the definitive biomarker, to date, the diagnosis of PD still relies mainly upon clinical symptoms. A wide range of treatments is available for PD, mainly alleviating the clinical symptoms. However, none of these current therapies can stop or even slow down the disease evolution. Hence, disease-modifying treatment is still a paramount unmet medical need. On the other side, bilirubin and its enzymatic machinery and precursors have offered potential benefits by targeting multiple mechanisms in chronic diseases, including PD. Nevertheless, only limited discussions are available in the context of neurological conditions, particularly in PD. Therefore, in this review, we profoundly discuss this topic to understand bilirubin’s therapeutical potential in PD
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