Polyamine deprivation provokes an antalgic effect

Kergozien, S; Jy, Bansard; Delcros, Jean‐Guy; Havouis, R; Jp, Moulinoux

doi:10.1016/0024-3205(96)00215-9

Cited by 22 publications

(7 citation statements)

References 19 publications

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“…The synthetic diet was prepared with products from Sigma Chemical Co. (Sigma, France) according to the formulation of Kergozien et al [17]. Two different synthetic diets were used in this study: (1) a normal diet providing an equivalent amount of polyamines to normal rat chow (54 mg/kg putrescine, 37 mg/kg cadaverine, 27 mg/kg spermidine and 7 mg/kg spermine) and fulfilling all rodent nutritional needs [17]; (2) a polyamine-deficient diet (PDD) equivalent to normal rodent chow but containing less than 10 µg/kg of polyamines.…”

Section: Methodsmentioning

confidence: 99%

A Polyamine-Deficient Diet Prevents Oxaliplatin-Induced Acute Cold and Mechanical Hypersensitivity in Rats

et al. 2013

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BackgroundOxaliplatin is an anticancer drug used for the treatment of advanced colorectal cancer, but it can also cause painful peripheral neuropathies. The pathophysiology of these neuropathies has not been yet fully elucidated, but may involve spinal N-methyl-D-aspartate (NMDA) receptors, particularly the NR2B subunit. As polyamines are positive modulators of NMDA-NR2B receptors and mainly originate from dietary intake, the modulation of polyamines intake could represent an interesting way to prevent/modulate neuropathic pain symptoms by opposing glutamate neurotransmission.MethodsThe effect of a polyamine deficient diet was investigated in an animal model of oxaliplatin-induced acute pain hypersensitivity using behavioral tests (mechanical and cold hypersensitivity). The involvement of spinal glutamate neurotransmission was monitored by using a proton nuclear magnetic resonance spectroscopy based metabolomic approach and by assessing the expression and phosphorylation of the NR2B subunit of the NMDA receptor.ResultsA 7-day polyamine deficient diet totally prevented oxaliplatin-induced acute cold hypersensitivity and mechanical allodynia. Oxaliplatin-induced pain hypersensitivity was not associated with an increase in NR2B subunit expression or phosphorylation, but with an increase of glutamate level in the spinal dorsal horn which was completely prevented by a polyamine deficient diet. As a validation that the oxaliplatin-induced hypersensitivity could be due to an increased activity of the spinal glutamate system, an intrathecal administration of the specific NR2B antagonist, ifenprodil, totally reversed oxaliplatin-induced mechanical and cold hypersensitivity.ConclusionA polyamine deficient diet could represent a promising and valuable nutritional therapy to prevent oxaliplatin-induced acute pain hypersensitivity.

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Section: Methodsmentioning

confidence: 99%

A Polyamine-Deficient Diet Prevents Oxaliplatin-Induced Acute Cold and Mechanical Hypersensitivity in Rats

et al. 2013

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“…Furthermore, the polyamine binding sites of NMDA receptor were heterogeneous in human cerebral cortex, and show a high degree of regional and individual variability, reflecting differences in ion channel activity [135]. Consequences of polyamine function at these neural cell receptors may include an analgesic effect due to polyamine deprivation [136]. A comprehensive review of the role of polyamines in neurochemistry was recently published [14].…”

Section: Effect Of Polyamines On Ligand-receptor Interactionsmentioning

confidence: 99%

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

Thomas¹

2001

CMLS, Cell. Mol. Life Sci.

780

577

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Polyamines are aliphatic cations with multiple functions and are essential for life. Cellular polyamine levels are regulated by multiple pathways such as synthesis from amino acid precursors, cellular uptake mechanisms that salvage polyamines from diet and intestinal microorganisms, as well as stepwise degradation and efflux. Investigations using polyamine biosynthetic inhibitors indicate that alterations in cellular polyamine levels modulate normal and cancer cell growth. Studies using transgenic mice overexpressing polyamine biosynthetic enzymes support a role of polyamines in carcinogenesis. Many, if not all, signal transduction pathways intersect with polyamine biosynthetic pathways and the regulation of intracellular polyamine levels. Direct binding of polyamines to DNA and their ability to modulate DNA-protein interactions appear to be important in the molecular mechanisms of polyamine action in cell proliferation. Consistent with the role of polyamines as facilitators of cell growth, several studies have shown their ability to protect cells from apoptosis. However, polyamines also have a role in facilitating cell death. The basis of these diverse cellular responses is currently not known. Cell death response might be partly mediated by the production of hydrogen peroxide during polyamine catabolism. In addition, the ability of polyamines to alter DNA-protein and protein-protein interactions might be disruptive to cellular functions, when abnormally high levels are accumulated due to defects in polyamine catabolic or efflux pathways. A large body of data indicates that polyamine pathway can be a molecular target for therapeutic intervention in several types cancers. Inhibitors of biosynthesis, polyamine analogues as well as oligonucleotide/polyamine analogue combinations are promising drug candidates for chemoprevention and/or treatment of cancer.

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“…Pain control in patients with rising PSA cannot be explained by a reduced tumour burden. One explanation might be due to PA deprivation itself, which has indeed been shown to provoke analgesic effects in animals submitted to painful stimuli [18,19]. Furthermore, the impact of the regimen on quality of life is outlined by a progressive degradation of performance status and pain after the regimen is stopped.…”

Section: Discussionmentioning

confidence: 98%

Polyamine-reduced diet in metastatic hormone-refractory prostate cancer (HRPC) patients

Cipolla

Guilhot

Moulinoux

2003

Biochemical Society Transactions

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Polyamine (PA) deprivation is effective in prostate carcinoma models. We have assessed the observance by patients, tolerance and side effects of a PA-reduced diet (PRD) and intestinal decontamination (ID), in order to reduce PA dietary and intestinal bacterial pools, in metastatic, hormone-refractory prostate cancer (HRPC) patients. A total of 13 volunteers (mean age, 67+/-10 years) with metastatic HRPC were proposed for PRD and ID (0.75 g/day of oral neomycin every other week). The mean time from HRPC diagnosis to the start of the diet was 12+/-8 months. Of the total 13, seven patients had received prior chemotherapy or Estramustine phosphate. PRD was obtained after HPLC assessment of PA contents in current foods and given 5 days a week. Toxicity, performance and pain status were assessed according to the World Health Organisation and EORTC scales. Prostatic specific antigen (PSA), blood counts, ionograms, transaminases and erythrocyte PA spermidine (Spd) and spermine (Spm; assessed by HPLC) were evaluated regularly. Mean observance was 8+/-7 months (range, 2-26 months). One case of grade II toxicity to neomycin was observed. Cancer-specific survival (after the diet) was 14+/-7 months, and two patients are still alive. All the other patients have died of their cancer at 12+/-6 months (range, 4-20 months). Cancer-specific survival after hormonal escape was 27+/-11 months (range, 9-45 months). Performance status was improved during the regimen and deteriorated 3 months after stopping. Pain score was improved (1.3 versus 0.6; P =0.04) during the diet and increased (2.1 versus 0.3) 3 months after stopping. Erythrocyte Spd (11.6+/-7 versus 7.7+/-2 nmol/8 x 10(9) erythrocytes; P =0.036) and Spm (7+/-6 versus 3.9+/-1.6 nmol/8 x 10(9) erythrocytes; P =0.036) levels were significantly reduced at 3 months. One patient had a >50% reduction in PSA, three patients had PSA stabilization for 6 months. PSA progression was observed in all other patients. No significant modification of other studied biological parameters was noted. Reducing PA dietary intake and ID is a well-observed and tolerated regimen and seems to be beneficial for patient quality of life and pain control. Patients with low initial PSA can experience durable stabilization. These encouraging results in such an aggressive disease certainly warrant further investigation.

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Polyamine deprivation provokes an antalgic effect

Cited by 22 publications

References 19 publications

A Polyamine-Deficient Diet Prevents Oxaliplatin-Induced Acute Cold and Mechanical Hypersensitivity in Rats

A Polyamine-Deficient Diet Prevents Oxaliplatin-Induced Acute Cold and Mechanical Hypersensitivity in Rats

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

Polyamine-reduced diet in metastatic hormone-refractory prostate cancer (HRPC) patients

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