Role of leukotrienes on hepatic ischemia/reperfusion injury in rats

Takamatsu, Yuji; Shimada, Kunio; Chijiiwa, Kazuo; Kuroki, Shin-Ichiro; Yamaguchi, Koji; Tanaka, Masao

doi:10.1016/j.jss.2003.07.004

Cited by 48 publications

(24 citation statements)

References 29 publications

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“…Furthermore, cysteinyl LTs are generated in the liver during the reperfusion period and may contribute to the development of hepatic edema and exert cytotoxicity (Takamatsu et al, 2004). Although inhibition of FLAP abrogated experimental liver injury (Titos et al, 2005) and decreased hepatic inflammation and fibrosis in mice (Horrillo et al, 2007), montelukast was also found to be effective in prevention of liver and intestine injury by reducing apoptosis and oxidative stress in a hepatic ischemia-reperfusion injury model (Daglar et al, 2009) and to improve hepatic fibrosis in cholestatic rats (ElSwefy and Hassanen, 2009).…”

Section: Cyslt In Other Diseasesmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

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Section: Cyslt In Other Diseasesmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Bäck¹,

Dahlén²,

Drazen³

et al. 2011

Pharmacol Rev

130

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“…Previous studies have shown that cysteinyl LTs are associated with hepatic I/R injury [17][18][19][20][21] . It is known that LTC4 synthesis enzymes including LTC4 synthase (LTC4S), microsomal glutathione S-transferase (MGST) 2 and MGST3 can conjugate LTA4 and reduced glutathione to form LTC4, which is the first committed synthesis step of the cysteinyl LTs, LTC4, LTD4, and LTE4 [22,23] .…”

mentioning

confidence: 99%

Sodium Nitroprusside Regulates mRNA Expressions of LTC4 Synthesis Enzymes in Hepatic Ischemia/Reperfusion Injury Rats via NF-κB Signaling Pathway

Yang¹,

Chen²,

Kong³

et al. 2007

Pharmacology

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Leukotriene (LT) C4 (LTC4) synthesis enzymes including LTC4 synthase (LTC4S), microsomal glutathione S-transferase (MGST) 2 and MGST3 can all conjugate LTA4 and reduced glutathione (GSH) to form LTC4, which is related to hepatic ischemia/reperfusion (I/R) injury. The relationship between nitric oxide (NO) and cysteinyl LTs has been shown in previous studies. However, the mechanisms of NO action on gene expression of LTC4 synthesis enzymes are still largely unclear during hepatic I/R. Adult male Sprague-Dawley rats were divided into 5 groups: a sham group (control), an I/R group, and sodium nitroprusside (SNP, 2.5, 5 and 10 µg/kg/min) + I/R groups. Livers were subjected to 60 min of partial hepatic ischemia followed by 5 h of reperfusion, saline or SNP (2.5, 5 and 10 µg/kg/min) administered intravenously. The mRNA levels of LTC4 synthesis enzymes, inducible NO synthase (iNOS) and endothelial No synthase (eNOS) in rat liver tissue were examined by RT-PCR; the protein expressions of NF-ĸB p65, p50 and IĸBα in liver cell lysates and nuclear extracts were detected by Western blot analysis, and serum NO₂· levels were also evaluated. Serum NO₂· levels, the protein expressions of NF-ĸB p65 and p50 in the nucleus extract, and hepatic mRNA expressions of LTC4S and iNOS were decreased while hepatic mRNA of eNOS was increased in the SNP (5 and 10 µg/kg/min) + I/R groups when compared with those in the I/R group. SNP (2.5 µg/kg/min) promoted the mRNA expressions of both MGST2 and MGST3, whereas SNP (10 µg/kg/min) increased MGST2 mRNA but decreased MGST3 mRNA compared to those in I/R group. Compared with control, the mRNA expression of MGST2 and MGST3 were elevated in SNP (2.5 µg/kg/min) + I/R group, MGST3 mRNA was significantly declined in the SNP (5 and 10 µg/kg/min) + I/R groups. Immunohistochemistry staining revealed that I/R liver exhibited strong cytoplasmic and nuclear staining for NF-ĸB p65, but the livers of the SNP (2.5 µg/kg/min) + I/R group presented slight cytoplasmic and nuclear staining. But IĸBα protein in all groups remains unchanged. It was concluded that SNP downregulated LTC4S mRNA expression by inhibiting NF-ĸB activation independent of IĸBα, but appeared to have a dual influence on the mRNA expressions of MGST2 and MGST3 by other signaling pathways during hepatic I/R injury.

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“…20,25,26,29 Data in the literature reveal that other types of eicosanoids, including leukotrienes (LTs) and F 2 -isoprostanes (F 2 -IsoPs), may mediate tissue damage in several models of liver injury. 20,40,41 It has been shown that cysteinyl LTs (LTC 4 , LTD 4 and LTE 4 ) may contribute to the development of ischemia-reperfusion liver injury in rats by causing vasoconstriction, tissue edema and cell toxicity 42 and that LTB 4 /LTB 4 receptor pathway mediates hepatic microcirculatory dysfunction in a murine model of endotoxemia. 20,43 Accordingly, inhibition of the enzyme 5-lipoxygenase, which is responsible for the generation of LTs from arachidonic acid, promoted liver regeneration and decreased hepatocyte injury in LPS and CCl 4 -treated laboratory animals.…”

Section: Discussionmentioning

confidence: 99%

Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

et al. 2011

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Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX) A 2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP) is a major cause of acute liver failure in the Western world. We investigated whether TXA 2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT) in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX) B 2 antibodies (anti-TXB 2 ) and a selective inhibitor of thromboxane (TX) synthase, benzylimidazole (BZI), were significantly hepatoprotective, while a selective thromboxane receptor (TPR) antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA 2 , TXB 2 , and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA 2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB 2 . According to our results, this protection is mediated, at least in part, through decreased production of TXB 2 by liver fragments ex vivo.

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Role of leukotrienes on hepatic ischemia/reperfusion injury in rats

Cited by 48 publications

References 29 publications

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

Sodium Nitroprusside Regulates mRNA Expressions of LTC4 Synthesis Enzymes in Hepatic Ischemia/Reperfusion Injury Rats via NF-κB Signaling Pathway

Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

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