Multiple systems organ failure—Modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells

Reversal of severe parenteral nutrition-associated liver disease in an infant with short bowel syndrome using parenteral fish oil (Omega-3 fatty acids)

“…The pathogenesis of hepatic dysfunction associated with TPN in children is still unclear. The basic and clinical studies performed till date suggest multifactorial risk factors such as prematurity [10][11][12][13], lack of enteral feeding [14][15][16][17], systemic or portal endotoxemia [18][19][20], reduced levels of gastrointestinal hormones [16], major abdominal surgery or multiple laparotomies [21,22], toxic bile acids such as lithocholic acid [23,24], carbohydrate overloading, aminoacid excess or imbalance [25][26][27], abnormal metabolism of fat [28], and presence of phytosterols in intravenous fat emulsions [29], as possible contributing factors. None of the theories on the etiology of PNAC in infants has so far led to a reliable means of treating or preventing it apart from stopping the TPN after a few weeks that is not always possible.…”

Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction

“…It is further reported that LPSactivated KC are toxic to hepatocytes due to diminution of hepatocyte protein synthesis [24,28]. This modulation of hepatocyte function by KC has been suggested to represent at least in part the mechanism of LPS-induced hepatic insufficiency [24]. Concomitantly, leukocytes play an active role in mediating some of the tissue damage observed in endotoxinemia.…”

“…LPS potentially renders KC cytotoxic, which then might contribute to liver injury following LPS exposure [36,37]. It is further reported that LPSactivated KC are toxic to hepatocytes due to diminution of hepatocyte protein synthesis [24,28]. This modulation of hepatocyte function by KC has been suggested to represent at least in part the mechanism of LPS-induced hepatic insufficiency [24].…”

“…Sugino and coworkers have demonstrated preservation of energy rich phosphates and prevention of oxidative stressinduced lipid peroxidation by vitamin E in endotoxemic mice [10]. Although it is well known that both activated Kupffer cells and leukocytes mediate endotoxin-induced hepatic organ dysfunction and failure [8,[24][25][26][27][28][29], there is no information available as to whether antioxidative intervention with vitamin E has the potential to prevent the manifestation of microvascular and parenchymal injury. Therefore, we studied the effect of vitamin E on endotoxin-induced non-parenchymal cell activation, hepatic nutritive perfusion failure and liver dysfunction using intravital fluorescence microscopy.…”

Effects of Biliary Obstruction on the Endocytic Activity in Hepatocyte and Liver Sinusoidal Endothelial Cells in Rats

“…Several investigators have reported that obstructive jaundice impairs Kupffer cell-phagocytic ac tivity [3][4][5][6][7][8][9]. Elevated bile acids disturb the Kupffer cell function [30][31][32], Endotoxin is mainly taken up by Kupffer cells [33] and a large dose of endotoxin suppresses the phago cytic activity in the cells [34], Therefore, it is conceivable that toxic agents including bile acids and endotoxins, which are highly ele vated in the circulation, may initially impair the function of Kupffer cells, but not endothe lial cells. It has also been reported that the uptake of rhodamine 123, which was used to assess the mitochondrial function, was 14-fold higher in Kupffer cells than in endothelial cells [35], The metabolic response of Kupffer cells to phagocytic challenge is higher than that of endothelial cells [36].…”