Disease relevance of trichlorogadolinium

• Scanning and transmission electron-microscopic examination of the rat liver sinusoid was performed in this study after in vivo treatment of rats with gram-negative bacterial lipopolysaccharide (LPS, 1 mg/Kg(-1) body weight), with or without pretreatment with gadolinium chloride (GdCl3 10 mg(Kg(-1) body weight) [1].
• Pretreatment with gadolinium chloride (GdCl3), which reduces KC function, attenuated the liver leukostasis and NPS elicited by gut I/R [2].
• Using a porcine endotoxemia model, animals were randomized to receive either GdCl3 (10 mg/kg or 30 mg/kg; n = 8 in each group) or vehicle saline (n = 8) 24 h before exposure to endotoxin [3].
• Gadolinium chloride (GC), which inhibits Kupffer cell activity, was administered to mice 48 and 24 h prior to ischemia [4].
• However, if rats were pretreated with gadolinium chloride (GdCl3), an inhibitor of Kupffer cell function, the CCl4-induced edema was greatly decreased [5].

High impact information on trichlorogadolinium

• (4) GdCl3 pretreatment protects against hepatotoxicity, decreases TNF-alpha, but increases IL-10 serum concentrations [6].
• Increased IL-10 and decreased TNF-alpha secretion are potentially involved in the hepatoprotection observed after GdCl3 pretreatment [6].
• METHODS: The effects of recombinant IL-10 (rIL-10), anti-IL-10 monoclonal antibodies, or gadolinium chloride (GdCl3) pretreatment were studied in mice challenged with Gal/LPS [6].
• Pretreatment with GdCl3/heparin further decreased CINC production by Kupffer cells compared with that of cells from animals that were pretreated with heparin or GdCl3 alone [7].
• We investigated the role of hepatic macrophages in the inflammatory response following reperfusion injury by blocking Kupffer cell phagocytosis with gadolinium chloride (GdCl3) [7].

Biological context of trichlorogadolinium

• Transient macrophage inhibition, particularly in hepatic Kupffer cells, is associated with significant prolongation of graft survival after intraportal islet allotransplantation (ITx) in rats: 7.2 days in the control group versus 11.9 days in the GdCl3 group (P < 0.01) and 15.6 days in the Cl2MDP group (P < 0.0006), respectively [8].
• When LEW donors were treated with GdCl3, which is known to block Kupffer cell phagocytosis and antigen processing, the spontaneous acceptance of the LEW liver grafts by DA recipients was unaffected [9].
• Pretreatment with GdCl3 resulted in a dose dependent reduction in early hepatic oxygen consumption as well as oxygen extraction ratio in response to continuous infusion of endotoxin [3].
• RESULTS: GdCl3 could selectively cause apoptosis of KC and obvious reduction of KC's activity, but no hepatotoxicity was observed [10].
• Kupffer cell number was reduced by prior (48 hours) treatment of mice with gadolinium chloride (GdCl2, 10 mg/kg of body weight, intravenously) or saline vehicle [11].

Anatomical context of trichlorogadolinium

• Kupffer cells were inactivated by twice weekly treatment with gadolinium chloride (GdCl3), a selective Kupffer cell toxicant [12].
• Coupled with previous experimental data, showing similar effects of GdCl3 on one of the hepatic sinusoidal endothelial cell (SEC) functions, i.e., hyaluronan scavenging, the data presented in this study strongly support the view that Kupffer cells modulate both the hepatic SEC's functional as well as ultrastructural properties [1].
• HPc, but not GdCl3 treatment, also reduced the number of liver CD4+ T lymphocytes and their interferon-gamma production [13].
• GdCl3 reduced these cytokines in the early but not the later phase and did not reduce neutrophil accumulation or improve the recipient survival [13].
• Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group [14].

Associations of trichlorogadolinium with other chemical compounds

• In addition, pretreatment with GdCl3/heparin further inhibited the rise in the serum levels of CINC following reperfusion compared with those in untreated animals (P < .01) [7].
• However, the administration of higher doses of GdCl3 (40 mg/kg) caused both hepatotoxicity and Kupffer cell necrosis, as well as an increased release of TNF, NO, and PGE2 in the liver [15].
• When donor rats were treated with gadolinium chloride (GdCl3, 10 mg/kg i.v. 24 h before storage of the liver) to inactivate the Kupffer cells, AST levels only rose to around 700 U/l, and the total bilirubin level was in the normal range (< 4 micromol/l) [16].

Gene context of trichlorogadolinium

• The increases in ET-1 and ETB mRNA were not prevented by the GdCl3 pretreatment [17].
• The mRNA levels for iNOS and eNOS significantly increased within the I/R group with no significant difference between the I/R group and the GdCl3-treated I/R group [17].
• The results indicated that GdCl2 treated mice exhibited a marked reduction in circulating IL-6 levels at both 2 and 24 hours after CLP [11].
• HO-1 mRNA expression significantly increased in the I/R group and this increase was attenuated by GdCl3 [17].
• Moreover, we found that Kupffer cell function and the NO, PGE2 and cAMP contents, as well as PKC and NF-kappaB p65 levels in the liver were only partially, but not fully recovered in up to six days following 20 mg/kg GdCl3 injection [15].

Analytical, diagnostic and therapeutic context of trichlorogadolinium

• The LEW liver donor was treated by TBI (10 gray) 7 days before transplantation, or LEW donor Kupffer cell phagocytosis was blocked with GdCl3 (7 mg/kg) on days -2 and -1 pretransplant [9].
• Macrophage infiltration was decreased in concordant and discordant GdCl-treated xenografts at day 4 compared with controls [18].
• Rats were given saline or gadolinium chloride (GdCl3), a KC toxicant, 24 h before cecal ligation and puncture (CLP) [19].
• We evaluated the effect of donor treatment with total body irradiation (TBI) or gadolinium chloride (GdCl3), and recipient treatment with exogenous IL-2 after transplantation on the survival of the spontaneously accepted liver grafts [9].
• In eight pig liver transplantations, the donors received 20 mg/kg of GdCl3 24 h before explantation, while controls (n = 8) received normal saline [20].

References