Pyrrolidine dithiocarbamate protects against thioacetamide-induced fulminant hepatic failure in rats

Bruck, Rafael; Aeed, Hussein; Schey, Ron; Matas, Zipora; Reifen, Ram; Zaiger, G.; Hochman, Ayala; Avni, Yona

doi:10.1016/s0168-8278(01)00290-2

Cited by 68 publications

(57 citation statements)

References 49 publications

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“…Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit IκB from the latent cytoplasmic form of NF-κB in cells treated with phorbol ester, IL-1, LPS and TNF-α (Schreck et al, 1992). Because NF-κB activation has been implicated in the pathogenesis of cell injury in experimental models of liver damage, Bruck et al (2002) studied whether PDTC would prevent hepatic damage induced in a rat model of thioacetamide (TAA)-induced liver failure. They found that the intraperitoneal administration of PDTC attenuated acute liver damage and improved survival of TAA-treated rats.…”

Section: Pyrrolidine Dithiocarbamate In Acute and Chronic Liver Damagementioning

confidence: 99%

NF‐κB in liver diseases: a target for drug therapy

Muriel

2008

J of Applied Toxicology

148

106

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There are five nuclear factor-kB (NF-kB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis and apoptosis prevention. Several inhibitors of NF-kB, like caffeic acid, captopril, curcumin, pyrrolidine dithiocarbamate, resveratrol, silymarin and thalidomide, have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the liver. A link between inflammation and hepatocellular carcinoma through the NF-kB pathway has been observed, providing ample experimental support for the tumor-promoting function of NF-kB in various models of cancer. NF-kB has been associated with the induction of proinflammatory gene expression and has attracted interest as a target for the treatment of inflammatory disease. However, despite much attention being focused on the deleterious effects of NF-kB, activation of this factor during the resolution of inflammation is associated with the production of antiinflammatory molecules like interleukin (IL)-10 and the onset of apoptosis. This suggests that NF-kB has an antiinflammatory role in vivo involving the regulation of the resolution of inflammation. Also, NF-kB promotes liver regeneration by upregulating IL-6 and other molecules like hepatocyte growth factor. It has been postulated that the beneficial properties of NF-kB are due to p50 homodimers, whose activation prevents cholestatic and chronic liver injury. More basic understanding on the function of the diverse NF-kB factors is urgently needed in different physiological and pathological conditions, because depending on the subunit composition of the dimmer, the disease and the stage of the illness, inhibition of the factor may result in a beneficial or in a deleterious response. Copyright © 2008 John Wiley & Sons, Ltd.There are five nuclear factor-kB (NF-kB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis, and apoptosis prevention. Several inhibitors of NF-kB have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the

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Section: Pyrrolidine Dithiocarbamate In Acute and Chronic Liver Damagementioning

confidence: 99%

NF‐κB in liver diseases: a target for drug therapy

Muriel

2008

J of Applied Toxicology

148

106

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“…It has been reported that hydrogen peroxide is able to directly activate NF-B, and a variety of antioxidants and antioxidant enzymes, such as catalase, down-regulate TNF-␣-mediated NF-B activation (Schreck et al, 1991;Anderson et al, 1994). TA is a thiono-sulfur-containing compound that is commonly used for inducing fulminant hepatic failure (Bruck et al, 2002) and liver cirrhosis (Kamath et al, 1999) in animal models. During the biotransformation of TA, both flavin-containing monooxygenase (Chieli and Malvaldi, 1984) and cytochrome P450 reduce dioxygen to superoxide anion, which is then catalyzed to produce hydrogen peroxide.…”

Section: Luminescence-based Analysis Of Nf-b Activation 449mentioning

confidence: 99%

Analysis of In Vivo Nuclear Factor-κB Activation during Liver Inflammation in Mice: Prevention by Catalase Delivery

Hyoudou¹,

Nishikawa²,

Kobayashi³

et al. 2006

Mol Pharmacol

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Nuclear factor-B (NF-B) is a transcription factor that plays crucial roles in inflammation, immunity, cell proliferation, and apoptosis. Until now, there have been few studies of NF-B activation in whole animals because of experimental difficulties. Here, we show that mice receiving a simple injection of plasmid vectors can be used to examine NF-B activation in the liver. Two plasmid vectors, pNF-B-Luc (firefly luciferase gene) and pRL-SV40 (Renilla reniformis luciferase gene), were injected into the tail vein of mice by the hydrodynamics-based procedure, an established method of gene transfer to mouse liver. Then, the ratio of the firefly and R. reniformis luciferase activities (F/R) was used as an indicator of the NF-B activity in the liver. Injection of thioacetamide or lipopolysaccharide plus D-galactosamine increased the F/R ratio in the liver, and this was significantly (P Ͻ 0.001) inhibited by an intravenous injection of catalase derivatives targeting liver nonparenchymal cells. Imaging the firefly luciferase expression in live mice clearly demonstrated that the catalase derivatives efficiently prevented the NF-B-mediated expression of the firefly luciferase gene. Plasma transaminases and the survival rate of mice supported the findings obtained by the luminescence-based analyses. Thus, this method, which requires no genetic recombination techniques, is highly sensitive to the activation of NF-B and allows us to continuously examine the activation in live animals. In conclusion, this novel, simple, and sensitive method can be used not only for analyzing the NF-B activation in the organ under different inflammatory conditions but also for screening drug candidates for the prevention of liver inflammation.

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“…The complex [PtCl(ESDT)(Py)] showed cytotoxic efficacy, the ability to overcome cisplatin resistance and low nephrotoxicity in respect to cisplatin [16,17], whereas the palladium analoge causes severe damages in the kidney [18]. The dithiocarbamates examined (essentially ESDT, Me 2 DT or Et 2 DT) do not present particular properties by themselves, apart from the general detoxicant ability, whereas pyrrolidine dithiocarbamate has been widely reported in the last three years owing to antioxidant, antiviral and antiinflammatory properties and metal transport in membranes [19][20][21][22][23][24]. We thought then, of interest to extend the study to such a particular dithiocarbamate.…”

Section: Introductionmentioning

confidence: 99%