Antibiotics prevent liver injury in rats following long-term exposure to ethanol

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

“…This connection was further confirmed when administration of LPS caused the progression of fatty liver into necroinflammatory changes in a rat model of alcoholic liver injury (Bhagwandeen et al, 1987;Pennington et al, 1997). In addition, elimination of intestinal bacteria or suppression of intestinal Gram negative bacteria attenuated alcoholic liver injury in rats by reducing plasma endotoxin levels (Adachi et al, 1995;Nanji et al, 1994). Normally, only a trace amount of endotoxin is absorbed from the intestine through the intestinal epithelial lining to the portal vein that carries it to the liver where it is cleared by Kupffer cells.…”

“…Serum endotoxin levels were elevated in rats with alcoholic liver injury developed after ethanol administration for 10 weeks by gavage (Keshavarzian et al, 2001). Similarly, plasma endotoxin levels were significantly elevated in rats with alcoholic liver injury developed in response to intragastric infusion of ethanol for 3-4 weeks (Nanji et al, 1994;Adachi et al, 1995). In mice, plasma endotoxin levels were significantly elevated 1.5 hour after intragastric administration of 6g/kg ethanol by gavage, and this was associated with significant small intestinal injury (Lambert et al, 2003).…”

“…In rats exposed to chronic ethanol in a liquid diet, administration of endotoxin led to the progression of liver injury from fatty liver to necro-inflammatory changes (Bhagwandeen et al, 1987;Pennington et al, 1997;Apte et al, 2005). In an intragstric infusion rat model of alcoholic liver injury, sterilization of intestine by antibiotics significantly attenuated liver injury by reducing plasma levels of endotoxin (Adachi et al, 1995), and in the same model, similar results were obtained by simultaneous feeding of probiotic lactobacillus GG bacteria (competitive inhibitor of Gram negative bacteria) to the rats (Nanji et al, 1994).…”

Cellular and molecular mechanisms in liver fibrogenesis

“…In alcoholic liver disease (ALD), Toll like receptors (TLRs) and mainly TLR4 have been reported to be involved in tissue damage as shown by employing TLR4 deficient mice [119], with a relevant role likely played by PAMPs since significant reduction in the bacterial load of the intestine resulted in a significant improvement of liver injury [120]. At present, just a single study has investigated specifically the role of inflammasome components in a rodent model of ethanolmediated liver injury [121].…”

Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll-like receptor 4

“…1,2 In the Tsukomoto and French model of rat alcoholic hepatitis, 3 the degree of liver injury is diminished by treatment with either antibiotics, lactobacillus, or polymixin, all of which decrease endogenous LPS. 4,5 In this model, Kupffer cells, when activated by LPS, play a prominent role in promoting liver injury. 6 Despite its potentially critical importance, the molecular mechanism by which Kupffer cells are activated by LPS remains largely unknown.…”