Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes

Fernández-Martínez, Amalia; Callejas, Nuria A.; Casado, Marta; Martı́n-Sanz, Paloma

doi:10.1016/j.jhep.2004.02.019

Cited by 30 publications

(11 citation statements)

References 44 publications

(57 reference statements)

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“…We adapted the rat model of acute liver failure induced by TAA to mice (Zimmermann et al ., 1989). The TAA model in mice has been extensively validated previously (Honda et al ., 2002; Fernández‐Martínez et al ., 2004; Schnur et al ., 2004). TAA was obtained from Sigma‐Aldrich (Rehovot, Israel) in powder form and dissolved in sterile normal saline (NS) solution; it was injected i.p.…”

Section: Methodsmentioning

confidence: 99%

Cannabidiol improves brain and liver function in a fulminant hepatic failure‐induced model of hepatic encephalopathy in mice

Avraham

Grigoriadis

Poutahidis

et al. 2011

British J Pharmacology

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BACKGROUND AND PURPOSEHepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACHFemale Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTSNeurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONSCannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain.

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Section: Methodsmentioning

confidence: 99%

Cannabidiol improves brain and liver function in a fulminant hepatic failure‐induced model of hepatic encephalopathy in mice

Avraham

Grigoriadis

Poutahidis

et al. 2011

British J Pharmacology

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“…As previously mentioned, COX-2 expression in liver appears to be restricted to very special conditions. In fact, COX-2 is transiently expressed in regenerating liver after PH or after challenge with potent hepatotoxic molecules, such as thioacetamide among other[44,45]. In addition to this, COX-2 expression has been observed in animal models of cirrhosis, in human and several (but not all) mouse hepatoma cell lines, after HBV or HCV infection and in human HCC[46-50].…”

Section: Cox-2 and Hccmentioning

confidence: 99%

Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

Martı́n-Sanz

Casado

2017

WJG

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The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases. Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically. Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.

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“…Moreover, several authors have reported that increased tissue COX-2 expression and PG production may contribute to the development of other cancers, including HCC (hepatocellular carcinoma) [7]. Expression of COX-2 has been demonstrated in many contexts related to liver cell pathologies: regeneration after partial hepatectomy [8,9], animal models of cirrhosis [10], human hepatoma cell lines [11,12], chronic hepatitis C infection [7,13] and HCC [14,15].…”

Section: Introductionmentioning

confidence: 99%

Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells

Fernández-Martínez

Mollá

Mayoral

et al. 2006

Biochemical Journal

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We have investigated the mechanism of COX-2 (cyclo-oxygenase 2)-dependent inhibition of apoptosis in liver, a key pathway underlying proliferative actions of COX-2 in liver cancers, cirrhosis, chronic hepatitis C infection and regeneration after partial hepatectomy. Stable expression of COX-2 in CHL (Chang liver) cells induced proliferation, with an increase in the proportion of cells in S-phase, but no other significant changes in cell-cycle distribution. This was associated with a marked inhibition of the apoptotic response to serum deprivation, an effect mimicked by treating empty-vector-transfected control cells (CHL-V cells) with prostaglandin E2 and prevented in COX-2-expressing cells (CHL-C cells) treated with selective inhibitors of COX-2. Serum-deprived CHL-V cells displayed several indicators of activation of intrinsic apoptosis: caspases 9 and 3 activated within 6 h and caspase 8 within 18 h, Bax expression was induced, cytochrome c was released to the cytosol, and PARP-1 [poly(ADP-ribose) polymerase 1] cleavage was evident in nuclei. COX-2 expression blocked these events, concomitant with reduced expression of p53 and promotion of Akt phosphorylation, the latter indicating activation of survival pathways. CHL cells were resistant to stimulation of the extrinsic pathway with anti-Fas antibody. Moreover, in vivo expression of GFP (green fluorescent protein)-labelled COX-2 in mice by hydrodynamics-based transient transfection conferred resistance to caspase 3 activation and apoptosis induced by stimulation of Fas.

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Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes

Cited by 30 publications

References 44 publications

Cannabidiol improves brain and liver function in a fulminant hepatic failure‐induced model of hepatic encephalopathy in mice

Cannabidiol improves brain and liver function in a fulminant hepatic failure‐induced model of hepatic encephalopathy in mice

Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells

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