Bacterial translocation in acute liver injury induced by d- galactosamine

Abstract

Acute liver injury and hepatic failure are serious Acute liver injury is associated with a high rate of infectious and septic complications. Most of these infec-clinical conditions that are sometimes observed in extions are produced by gram negative enteric bacteria. tensive hepatic surgery and in patients with multiple We evaluated bacterial translocation, intestinal perme-system organ failure. 1,2 Bacterial infection and sepsis ability, blood flow, portal pressure, and intestinal mi-are recognized as dangerous complications of this remcroflora after induction of liver injury and 70% liver re-edy with significant share in its morbidity and mortalsection in the rat. The rate of translocation to both portal ity. [3][4][5] Gram-negative enteric bacteria are frequent and arterial blood was 100% at 24 hours and 50% at 48 causative organisms in most of the published studies. 6-8 hours after liver resection compared with 83% to portal It has been shown that the gut, as a reservoir of enteric vein and 50% to aortic blood at both time points after bacteria in the body, plays an important role in many acute liver injury. Translocation to intraabdominal orcritical clinical situations, such as major burns, hemorgans (liver, spleen, and mesenteric lymph nodes) was rhagic shock, and so on. 9 Under normal conditions a 100% in both groups at both 24 and 48 hours. The rate series of protective measures, such as mucosal barrier of translocation increased after liver injury at 48 hours with progression of the liver injury but was decreased function, immunoglobulin secretion, and local and sysin the 70% liver resection group with improvement of temic macrophage system prevent translocation of liver function. ''Total aerobic'' and ''total anaerobic'' bac-these potential pathogens to the extraintestinal sites. 10 terial counts in small intestine and cecum were not af-Severe clinical disorders may disrupt these normal profected. Pulmonary, distal small intestine, and cecal tective mechanisms and make it possible for the intestiblood flow were decreased in both groups, whereas nal bacteria to translocate. Translocation of endotoxin blood flow in the proximal small intestine was unaf-and intestinal bacteria in acute liver injury may intenfected. Portal pressure and flow were increased after sify the extent of injury and may also be responsible 70% liver resection, but they were decreased in acute for the high rate of associated infection and sepsis obliver injury. After acute liver injury, permeability of both served in these patients. So far, little attention has MATERIALS AND METHODSgery, Lund University, 221 85 Lund, Sweden. Experimental Groups.One hundred eight Sprague-

Protective Effect of Pinitol againstD-Galactosamine-Induced Hepatotoxicity in Rats Fed on a High-Fat Diet

“…The production of TNF-from Kupffer cells, which are activated by endotoxin derived from the gut after GalN administration, is regarded as a significant event in the toxicity of GalN in vivo. [3][4][5][6] The increase in the serum TNF-level induced by GalN was significantly reduced by pinitol supplementation, which might have been due to its antiinflammatory effect, 12,13) and thus inhibited the production of TNF-from Kupffer cells.…”

“…TNFthen leads to cell death in various ways, including the promotion of oxidative stress and the inflammatory process. [3][4][5] This mechanism is thought to be central to the toxicity of GalN in vivo. 6) GalN inhibits macromolecule synthesis in hepatocytes, 7) increasing the sensitivity to TNF--mediated events.…”

HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure

“…Experimental hepatotoxicity is associated with high incidence of gut derived gram-negative bacterial infection [9, 40]. Acetaminophen overdose can induce evident gut BT and severe intestinal mucosal injury in mice [40], and gut bacteria can adhere to the injured mucosa, which is necessary but not sufficient to induce gut BT [40], because blockade of HMGB1 reduces 85% of gut BT, but it does not decrease gut mucosal permeability in experimental acetaminophen overdose [40].…”

“…Between 39% and 57% of ALF patients experience bacterial infection [8]. ALF has a high rate of infection with gram-negative enteric bacteria in animal model [9]. Gram-negative and gram-positive bacteria can elicit sepsis [7].…”

Effect of Lactobacilli on Paracellular Permeability in the Gut

“…D-galactosamine is a hepatocyte-specific inhibitor of RNA synthesis and has been shown to increase the sensitivity to LPS and to the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) [28]. Increased gut permeability after insult has been seen in the distal ileum and cecum by measuring the passage of Cr-EDTA, together with an increased amount of translocating bacteria in mesenteric lymphnodes and liver as compared to control animals without any injury [29]. As endotoxin is implicated in the progression of D-galactosamine-induced liver injury [30], simultaneous administration of LPS from Escherichia coli is often used in order to increase the severity of the model.…”