Anaesthetics modulate tumour necrosis factor α: effects of L‐carnitine supplementation in surgical patients. Preliminary results.

Delogu, Giovanna; Simone, Claudio De; Famularo, Giuseppe; Fegiz, Alessandra; Paoletti, Francesca; Jirillo, Emilio

doi:10.1155/s0962935193000730

Cited by 14 publications

(10 citation statements)

References 9 publications

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“…Inhibition of this effect by RU 486 indicated its GR dependence. These results are consistent with previous reports of decreased circulating cytokine levels in animal models of cachexia and septic shock, as well as in surgical and HIV patients, after LCAR administration 24–27. Thus, we propose that the immunomodulatory properties of LCAR are mediated, at least in part, by its interaction with the GRα.…”

Section: Discussionsupporting

confidence: 93%

“…Administration of LCAR to rodents markedly suppressed the lipopolysaccharide (LPS)‐induced cytokine production, improving their survival during cachexia and septic shock 24,25. Decreased serum levels of tumor necrosis factor α (TNFα) were detected in surgical and HIV‐infected patients after administration of high doses of LCAR 26–28. When administered at high concentrations to pregnant rats, LCAR showed an efficacy similar to that of 0.1‐0.2 mg/kg of betamethasone in promoting fetal‐lung maturation 29–31…”

Section: Introductionmentioning

confidence: 99%

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Modulatory Effects of l‐Carnitine on Glucocorticoid Receptor Activity

Manoli¹,

Martino²,

Kino³

et al. 2004

Annals of the New York Academy of Sciences

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L-carnitine (3-hydroxy-4-N,N,N-trimethylaminobutyrate) is a conditionally essential nutrient with a major role in cellular energy metabolism. It is available in the United States as both a prescription drug and an over-the-counter nutritional supplement. Accumulating evidence from both animal and human studies indicates that pharmacologic doses of L-carnitine (LCAR) have immunomodulatory effects resembling those of glucocorticoids (GC). On the other hand, in contrast to GC, which cause bone loss, LCAR seems to have positive effects on bone metabolism. To explore the molecular bases of this GC-like activity of LCAR, we investigated its effects on glucocorticoid receptor (GR)-modulated cytokine release ex vivo, and on the transcriptional activity, intracellular trafficking, and binding of GR in vitro. At high noncytotoxic doses, LCAR (a) suppressed the lipopolysaccharide-stimulated release of tumor necrosis factor alpha and interleukin-12 from primary human monocytes in a GC-like fashion, (b) stimulated the transcriptional activity of GR on the GC-responsive promoters, (c) triggered nuclear translocation of green fluorescent protein (GFP)-fused GR, and (d) reduced the whole cell binding of [(3)H]-dexamethasone to GR. These results suggest that LCAR is a "nutritional modulator" of the GR, by acting as an agonist-like compound. Since LCAR appears to have positive effects on bone metabolism, in contrast to GC, LCAR may share some of the therapeutic properties of GC, particularly on the immune system, but not their deleterious side effects on some of other organs/tissues. Thus, LCAR is potentially a useful alternative compound of GC in particular therapeutic situations. The clinical and therapeutic implications of these findings, as well as a better understanding of their mechanisms, warrant further research.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Modulatory Effects of l‐Carnitine on Glucocorticoid Receptor Activity

Manoli¹,

Martino²,

Kino³

et al. 2004

Annals of the New York Academy of Sciences

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“…Consistent experimental and clinical evidence suggests that L-carnitine may directly modify cytokine response. In surgical and in HIV-positive patients, L-carnitine administration lowered the circulating levels of cytokines Delogu et al 1993). Similarly, in rats exposed to LPS or methylcholanthrene, L-carnitine treatment blunted the increase in serum TNF-alpha (Winter et al 1995), whereas dietary supplementation with L-carnitine of ethanol-treated rats inhibited TNF-alpha production by Kupffer cells (Bykov et al 2003).…”

Section: Discussionmentioning

confidence: 95%

l-Carnitine induces recovery of liver lipid metabolism in cancer cachexia

et al. 2011

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Cancer cachexia causes metabolic alterations with a marked effect on hepatic lipid metabolism. L-Carnitine modulates lipid metabolism and its supplementation has been proposed as a therapeutic strategy in many diseases. In the present study, the effects of L-carnitine supplementation on gene expression and on liver lipid metabolism-related proteins was investigated in cachectic tumour-bearing rats. Wistar rats were assigned to receive 1 g/kg of L-carnitine or saline. After 14 days, supplemented and control animals were assigned to a control (N), control supplemented with L-carnitine (CN), tumour-bearing Walker 256 carcinosarcoma (TB) and tumour-bearing supplemented with L-carnitine (CTB) group. The mRNA expression of carnitine palmitoyltransferase I and II (CPT I and II), microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), fatty acid translocase (FAT/CD36), peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and organic cation transporter 2 (OCTN2) was assessed, and the maximal activity of CPT I and II in the liver measured, along with plasma and liver triacylglycerol content. The gene expression of MTP, and CPT I catalytic activity were reduced in TB, who also showed increased liver (150%) and plasma (3.3-fold) triacylglycerol content. L-Carnitine supplementation was able to restore these parameters back to control values (p<0.05). These data show that L-carnitine preserves hepatic lipid metabolism in tumour-bearing animals, suggesting its supplementation to be of potential interest in cachexia.

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“…43 In humans, an immunosuppressive role of L-carnitine is also observed with reduction of TNF-a levels in surgical and AIDS patients after receiving L-carnitine supplementation. 45,46 Like L-carnitine, betaine has also been reported to possess antiinflammatory properties. 38 Although the molecular events associated with the anti-inflammatory effects of L-carnitine or betaine in dry eye are not yet fully understood, we have demonstrated these activities also play a role in prevention and treatment of murine dry eye.…”

Section: Discussionmentioning

confidence: 99%