Inhibition of 5-lipoxygenase promotes the regeneration of the liver after partial hepatectomy in normal and icteric rats

Urade, Masaaki; Izumi, Ryohei; Kitagawa, Hirohisa

doi:10.1053/jhep.1996.v23.pm0008617435

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…Urade et al found that once Arachidonate 5-lipoxygenase activity is suppressed, the liver regenerative process may be facilitated. 26 The reduced expression of the gene at 30, 54, 96, and 168 h in the present study reflects the enhancement of liver regenerative activities at these time points. Spolarics et al suggested that prostaglandin can facilitate LR.…”

Section: Discussionmentioning

confidence: 47%

Relevance between lipid metabolism‐associated genes and rat liver regeneration

Lin²,

Qin³

2008

Hepatology Research

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According to the results of the chip detection, it was presumed that fatty acid synthesis at 24-66 h, leukotriene and androgen synthesis at 16-168 h, prostaglandin synthesis at 2-96 h, triglyceride synthesis at 18-24 h, glycosphingolipid synthesis at 0.5-66 h, metabolism of phosphatidyl inositol and sphingomyelin at 2-16 h, and cholesterol catabolism at 30-168 h were enhanced. Throughout almost the whole LR, the genes participating in estrogen, glucocorticoid, and progesterone synthesis, and triglyceride catabolism were upregulated, while phospholipid and glycosphingolipid catabolism were downregulated.

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Section: Discussionmentioning

confidence: 47%

Relevance between lipid metabolism‐associated genes and rat liver regeneration

Lin²,

Qin³

2008

Hepatology Research

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“…In fact, its potent antioxidant properties prevent loss of hepatocytes during liver regeneration [26]. Moreover, inhibition of 5-LO by AA861 appeared to stimulate liver regeneration after partial hepatectomy in rats [57]. In line, the first clinical application of a large single dose of melatonin prior to major liver resection was well tolerated by patients and was associated with a reduced stay at the ICU as well as total hospital stay [58].…”

Section: Discussionmentioning

confidence: 99%

Melatonin suppresses activation of hepatic stellate cells through RORα‐mediated inhibition of 5‐lipoxygenase

Shajari

Laliena

Heegsma

et al. 2015

Journal of Pineal Research

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Liver fibrosis is scar tissue resulting from an uncontrolled wound-healing process in response to chronic liver injury. Liver damage generates an inflammatory reaction that activates hepatic stellate cells (HSC) that transdifferentiate from quiescent cells that control retinol metabolism to proliferative and migratory myofibroblasts that produce excessive amounts of extracellular matrix proteins, in particular collagen 1a1 (COL1A1). Although liver fibrosis is reversible, no effective drug therapy is available to prevent or reverse HSC activation. Melatonin has potent hepatoprotective properties in a variety of acute and chronic liver injury models and suppresses liver fibrosis. However, it remains unclear whether melatonin acts indirectly or directly on HSC to prevent liver fibrosis. Here, we studied the effect of melatonin on culture-activated rat HSC. Melatonin dose-dependently suppressed the expression of HSC activation markers Col1a1 and alpha-smooth muscle actin (αSMA, Acta2), as well as HSC proliferation and loss of lipid droplets. The nuclear melatonin sensor retinoic acid receptor-related orphan receptor-alpha (RORα/Nr1f1) was expressed in quiescent and activated HSC, while the membranous melatonin receptors (Mtrn1a and Mtrn1b) were not. The synthetic RORα agonist SR1078 more potently suppressed Col1a1 and αSma expression, HSC proliferation, and lipid droplet loss, while the RORα antagonist SR1001 blocked the antifibrotic features of melatonin. Melatonin and SR1078 inhibited the expression of Alox5, encoding 5-lipoxygenase (5-LO). The pharmacological 5-LO inhibitor AA861 reduced Acta2 and Col1a1 expression in activated HSC. We conclude that melatonin directly suppresses HSC activation via RORα-mediated inhibition of Alox5 expression, which provides novel drug targets to treat liver fibrosis.

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“…Chemical mediators of fibrogenesis are proteolytic enzymes, lymphokines, monokines and collagen stimulating factors [4]. Macrophages within the granulomas secrete many mediators like prostaglandins (PGs) [5,6] and leukotrienes (LTs) [7,8] which have a pronounced role in mediation and modulation of inflammation [9,10]. In mice, liver fibrosis may regress if S. mansoni infection is cured at the early stage of the disease.…”

Section: Introductionmentioning

confidence: 99%

Effect of Combined Chemotherapy and Anti-inflammatory Drugs on Murine Schistosomiasis

Mahmoud

Zoheiry

Nosseir

2011

Arzneimittelforschung

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Hepatic granulomas resulting from Schistosoma mansoni infection contain high levels of prostaglandins (PG) and leukotrienes. The present experimental study was conducted to show the effect of murine S. mansoni infection on PGE2 level in the liver granuloma homogenate and to explore the possibility of using non-steroidal anti-inflammatory drugs (NSAIDs) namely, ibuprofen (CAS 15687-27-1) and naproxen (CAS 22204-53-1), either alone or in combination with praziquantel (CAS 55268-74-1) to induce regression of hepatic morbidity or to ameliorate the biochemical and histopathological consequences and intensity of infection. Infection with S. mansoni increased the level of alanine amino-transaminase (ALT), gamma glutamyl transferase (GGT), PGE2, hepatic collagen deposition, antibody titre and circulating schistosomal antigen. The last parameter was reduced significantly by progression of infection in the 11th and 16th weeks. Treatment with praziquantel was found to reduce the number of worms (97%), with complete absence of immature ova and increase in the number of dead ova. Also it reduced all the elevated parameters except PGE2. NSAIDs were found to reduce significantly the level of PGE2 at 9 weeks but not at 11 and 16 weeks post-infection. ALT and GGT were not significantly decreased compared to their corresponding controls. Treatment with ibuprofen or naproxen either alone or in combination with praziquantel or praziquantel alone reduced significantly the granuloma diameters. Collagen deposition and percentage of fibrotic area were significantly decreased compared to infected control but the antibody titre or circulating antigen levels were not affected. Combined therapy of praziquantel with ibuprofen or naproxen improved most of the parameters estimated and maintained the reducing effect on PGE2 at 11 and 16 weeks post-infection. So it can be concluded that in S. mansoni infection treatment with ibuprofen or naproxen is not preferable without treatment of schistosomiasis by using praziquantel.

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Inhibition of 5-lipoxygenase promotes the regeneration of the liver after partial hepatectomy in normal and icteric rats

Cited by 5 publications

References 21 publications

Relevance between lipid metabolism‐associated genes and rat liver regeneration

Relevance between lipid metabolism‐associated genes and rat liver regeneration

Melatonin suppresses activation of hepatic stellate cells through RORα‐mediated inhibition of 5‐lipoxygenase

Effect of Combined Chemotherapy and Anti-inflammatory Drugs on Murine Schistosomiasis

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