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Sepsis is a life-threatening clinical syndrome defined as a deregulated host response to infection associated with organ dysfunction. Mechanisms underlying the pathophysiology of septic liver dysfunction are incompletely understood. Among others, the iron containing tetrapyrrole heme inflicts hepatic damage when released into the circulation during systemic inflammation and sepsis. Accordingly, hemolysis and decreased concentrations of heme-scavenging proteins coincide with an unfavorable outcome of critically ill patients. As the liver is a key organ in heme metabolism and host response to infection, we investigated the impact of labile heme on sinusoidal microcirculation and hepatocellular integrity. We here provide experimental evidence that heme increases portal pressure via a mechanism that involves hepatic stellate cell-mediated sinusoidal constriction, a hallmark of microcirculatory failure under stress conditions. Moreover, heme exerts direct cytotoxicity in vitro and aggravates tissue damage in a model of polymicrobial sepsis. Heme binding by albumin, a low-affinity but high-capacity heme scavenger, attenuates heme-mediated vasoconstriction in vivo and prevents heme-mediated cytotoxicity in vitro. We demonstrate that fractions of serum albumin-bound labile heme are increased in septic patients. We propose that heme scavenging might be used therapeutically to maintain hepatic microcirculation and organ function in sepsis.
This article was published in the following journal.
Name: Archives of biochemistry and biophysics
Hepatic ischemia/reperfusion (I/R) injury is a serious complication that occurs upon hypovolemic shock, liver resection, and transplantation. A significant age-dependent difference in the injury respo...
Glucagon promotes hepatic glucose production maintaining glucose homeostasis in the fasting state. Glucagon maintains at high level in both diabetic animals and human, contributing to hyperglycemia. M...
Hepatic ischemia/reperfusion (IR) injury is a common medical phenomenon that occurs during a number of clinical conditions, such as liver transplantation, severe injuries, and shock. In our study, we ...
Chronic liver injury often results in activation of hepatic myofibroblasts and development of liver fibrosis. Hepatic myofibroblasts may originate from three major sources; Hepatic Stellate Cells (HSC...
The final common pathway of single ventricle patients is the Fontan procedure. Among the immediate postoperative complications is acute hepatic injury presented by marked elevation of liver enzymes (a...
Background: In patients undergoing hemodialysis or hemofiltration will suffer from the injury of reactive oxidative species. Oxidative stress will affect cell membrane, protein, and DNA. I...
The main objective is to study the effect of polyphenol supplementation on hepatic steatosis as measured by hepatic ultrasound, hepatic elastography and magnetic resonance hepatic spectros...
This is a Phase 1, single-centre, open-label, parallel-group study in subjects with moderate hepatic impairment and subjects with normal hepatic function. Child-Pugh (CP) scoring will be u...
Collection of Safety, Efficacy and Resource Utilization Information in Patients Who Have Received Melphalan PHP with the Delcath Hepatic Delivery System for the Treatment of Unresectable H...
The purpose of this study is to assess the pharmacokinetics, pharmacodynamics and safety after single oral administration of FYU-981 to subjects with hepatic insufficiency and with normal ...
A group of metabolic diseases due to deficiency of one of a number of LIVER enzymes in the biosynthetic pathway of HEME. They are characterized by the accumulation and increased excretion of PORPHYRINS or its precursors. Clinical features include neurological symptoms (PORPHYRIA, ACUTE INTERMITTENT), cutaneous lesions due to photosensitivity (PORPHYRIA CUTANEA TARDA), or both (HEREDITARY COPROPORPHYRIA). Hepatic porphyrias can be hereditary or acquired as a result of toxicity to the hepatic tissues.
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
Cholangiocarcinoma arising near or at the confluence of the right and left hepatic ducts (COMMON HEPATIC DUCT). These tumors are generally small, sharply localized, and seldom metastasizing.
A class of nongenotoxic CARCINOGENS that induce the production of hepatic PEROXISOMES and induce hepatic neoplasms after long-term administration.
Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.
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...
Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections. Sepsis is not just limited to the blood and can affect the whole body, including the organ...
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...