Protective effects of pyrrolidine dithiocarbamate on myocardium apoptosis induced by adriamycin in rats

Liu, Hongli; Gu, Haotian; Sun, Baogui

doi:10.1016/j.ijcard.2006.01.010

Cited by 20 publications

(11 citation statements)

References 27 publications

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“…Furthermore, PDTC has to be administred before the challenge, because it was ineffective in inhibiting NF-B when given concurrently with LPS. These findings have been strongly supported by other studies in which PDTC has been shown to downregulate the expression of NF-B controlled genes in vivo [237][238][239][240][241][242][243][244][245][246][247][248][249]. Moreover, PDTC can attenuate an acute injury even if it fails to inhibit NF-B [250][251].…”

Section: Inhibitors Of Nf-b Pathwaysupporting

confidence: 73%

Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals

Cvek

Dvořák²

2007

CPD

132

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Dithiocarbamates and their complexes with transition metals have been used as common pesticides, vulcanizing or analytical agents for decades. These compounds are one of the most reported inhibitors of nuclear factor-kappaB (NF-kappaB) signaling cascade. Recently, it has been found that dithiocarbamates are very potent inhibitors of proteasome. NF-kappaB plays a central role in the immune system and is described as a major actor in many of human cancers mainly because of its protective effects against apoptosis. Molecular mechanisms involved in regulation and function of NF-kappaB pathway have been elucidated recently. In particular, pivotal zinc containing proteins that alter NF-kappaB signal transduction were recognized. Additionally, proteasome system was found to be a key player in NF-kappaB pathway and is an attractive target for anticancer drug development. Collectively, the capability of dithiocarbamates to inhibit NF-kappaB and proteasome makes these compounds promising anticancer agents. This review focuses on the biological activity of dithiocarbamate coordination compounds with regard to their possible molecular targets in NF-kappaB signaling and proteasome (JAMM domain proteins). Future research should aim to find the most suitable dithiocarbamate coordination compounds for treatment of cancer and other diseases.

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Section: Inhibitors Of Nf-b Pathwaysupporting

confidence: 73%

Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals

Cvek

Dvořák²

2007

CPD

132

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“…In addition, PDTC can inhibit the NF-κB-mediated production of TNF-α, hypoxia-induced dephosphorylation of Akt, and inflammatory responses [102][103][104] . It has been shown that treatment with PDTC significantly attenuates reperfusion-induced lung injury [105] , glycerol-induced renal injury [106] , cholestatic liver injury [107] , and adriamycin-induced myocardial apoptosis [108] . Crack et al [109] observed that knockout glutathione peroxidase-1 (Gpx1) in mice increased the ischemia-induced activation of NF-κB.…”

Section: Nf-κb Inhibitors and Neuroprotective Therapymentioning

confidence: 99%

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

Qin

Tao

Chen

2007

Acta Pharmacologica Sinica

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NF-κB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-κB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-κB on cell survival could be protective or destructive, depending on types, developmental stages of cells, and pathological conditions. The complexity of NF-κB in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-κB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly associated with the inhibition of NF-κB, leading to speculation that blocking the pathological activation of NF-κB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-κB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-κB that are involved in cell death and survival to elucidate why NF-κB promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-κB inhibitors on neuroprotection in certain pathological conditions to speculate if NF-κB is a potential target for neuroprotective therapy.

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“…PDTC is a low-molecular-weight thiol compound that scavenges free reactive oxygen species by its metal-chelating properties [16]. In our previously studies, it was suggested that PDTC protects against myocardial apoptosis induced by acute ADR [17]. However, the role of PDTC on antioxidant enzyme in chronic ADR-induced cardiomyopathy remains to be understood.…”

Section: Introductionmentioning

confidence: 99%

Effects of Pyrrolidine Dithiocarbamate on Antioxidant Enzymes in Cardiomyopathy Induced by Adriamycin in Rats

Liu²,

Li³

et al. 2008

Cardiology

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Objective: The clinical usefulness of adriamycin (ADR) is restricted by the frequent induction of dose-dependent chronic cardiomyopathy. Previous studies on ADR cardiotoxicity have reported that the formation of free reactive oxygen radicals might be involved in ADR cardiotoxicity. Pyrrolidine dithiocarbamate (PDTC) is a potent antioxidant in vivo and in vitro. The present study was undertaken to examine the effects of PDTC on antioxidant enzymes in cardiomyopathy induced by ADR in rats. Methods: Thirty-two male Wistar rats were randomly divided into 4 groups: control, ADR, PDTC, and ADR+PDTC. After 30 days, myocardial histopathological and electron microscopic examinations were performed: the myocardial content of superoxide anion and lipid peroxides were examined; the myocardial total antioxygenation capability (T-AOC) and activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were examined; myocardial GSH-Px, Mn-SOD and Cu,Zn-SOD gene expressions were examined by RT-PCR analysis, and the myocardial expression of GSH-Px, Mn-SOD and Cu,Zn-SOD proteins was assessed by Western blot analysis. Results: At 30 days, ADR-induced cardiomyopathy was confirmed by structural examination. The changes were prevented by PDTC. Myocardial superoxide anion and lipid peroxides were increased by ADR, and these changes were also inhibited by PDTC. ADR decreased myocardial T-AOC and the activity of GSH-Px and SOD, and these changes were likewise inhibited by PDTC. mRNA and protein expression of GSH-Px and Mn-SOD were depressed by ADR treatment and prevented by PDTC. Cu,Zn-SOD mRNA and protein levels were not significantly changed by ADR or PDTC. Conclusion: PDTC prevented ADR cardiomyopathy in rats by upregulating GSH-Px and SOD activation, which is associated with changes in the expression of GSH-Px and Mn-SOD transcript and protein levels.

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Protective effects of pyrrolidine dithiocarbamate on myocardium apoptosis induced by adriamycin in rats

Cited by 20 publications

References 27 publications

Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals

Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

Effects of Pyrrolidine Dithiocarbamate on Antioxidant Enzymes in Cardiomyopathy Induced by Adriamycin in Rats

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Protective effects of pyrrolidine dithiocarbamate on myocardium apoptosis induced by adriamycin in rats

Cited by 20 publications

References 27 publications

Targeting of Nuclear Factor-&#954;B and Proteasome by Dithiocarbamate Complexes with Metals

Targeting of Nuclear Factor-&#954;B and Proteasome by Dithiocarbamate Complexes with Metals

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

Effects of Pyrrolidine Dithiocarbamate on Antioxidant Enzymes in Cardiomyopathy Induced by Adriamycin in Rats

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Product

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Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals

Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals