Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1993;2(7):S57–S62. doi: 10.1155/S0962935193000778

Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFα

Ingrid M Garrelds 1,✉, Graham R Elliott 2, Wanda M Pruimboom 1, Freek J Zijlstra 1, Iván L Bonta 1
PMCID: PMC2365447  PMID: 18475573

Abstract

THE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect of 4 days feeding of 300 mg/kg/day of L-carnitine, acetyl Lcarnitine and propionyl L-carnitine on the basal and calcium ionophore (A23187) stimulated release of arachidonic acid metabolites from rat carrageenin elicited peritoneal cells was investigated. There were two series of experiments carried out. In the first, the harvested peritoneal cell population consisted of less than 90% macrophages and additional polymorphonuclear (PMN) leucocytes. The basal release of prostaglandin E2 (PGE2), 6-ketoprostaglandin F1α (6-keto-PGF1α) and leukotriene B4 (LTB4) was stimulated by all treatments. The A23187 stimulated release of 6-keto-PGF1α and LTB4 was increased by all three compounds. The 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were increased by carnitine treatment. These results suggested that carnitine could modify the macrophage component of an inflammatory site in vivo. In the second series of experiments the harvested cell population was highly purified (>95% macrophages) and none of the compounds fed to the rats caused a change of either eicosanoid or TNFα formation. Moreover the 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were not enhanced by any of the compounds tested. It is conceivable that in the first series the increased ratios 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 reflected the effect of carnitine or its congeners on PMN leucocytes rather than on macrophages.

Full Text

The Full Text of this article is available as a PDF (508.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Christophersen B. O., Norseth J. Arachidonic acid synthesis in isolated liver cells:" effects of (-)-carnitine and of (+)-decanoylcarnitine. FEBS Lett. 1981 Oct 26;133(2):201–204. doi: 10.1016/0014-5793(81)80505-4. [DOI] [PubMed] [Google Scholar]
  2. Conte A., Fraticelli G., Ronca G. Recent findings on the regulatory functions of CoA and the normalizing activity on plasma lipids of exogenous CoA. Drugs Exp Clin Res. 1992;18(5):179–188. [PubMed] [Google Scholar]
  3. Elliott G. R., Lauwen A. P., Bonta I. L. The effect of acute feeding of carnitine, acetyl carnitine and propionyl carnitine on basal and A23187-stimulated eicosanoid release from rat carrageenan-elicited peritoneal macrophages. Br J Nutr. 1990 Sep;64(2):497–503. doi: 10.1079/bjn19900049. [DOI] [PubMed] [Google Scholar]
  4. Fieren M. W., van den Bemd G. J., Ben-Efraim S., Bonta I. L. Prostaglandin E2 inhibits the release of tumor necrosis factor-alpha, rather than interleukin 1 beta, from human macrophages. Immunol Lett. 1992 Jan;31(1):85–90. doi: 10.1016/0165-2478(92)90015-g. [DOI] [PubMed] [Google Scholar]
  5. McGarry J. D., Robles-Valdes C., Foster D. W. Role of carnitine in hepatic ketogenesis. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4385–4388. doi: 10.1073/pnas.72.11.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Murakami R., Momota T., Yoshiya K., Yoshikawa N., Nakamura H., Honda M., Ito H. Serum carnitine and nutritional status in children treated with continuous ambulatory peritoneal dialysis. J Pediatr Gastroenterol Nutr. 1990 Oct;11(3):371–374. doi: 10.1097/00005176-199010000-00015. [DOI] [PubMed] [Google Scholar]
  7. Renz H., Gong J. H., Schmidt A., Nain M., Gemsa D. Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. J Immunol. 1988 Oct 1;141(7):2388–2393. [PubMed] [Google Scholar]
  8. Schepers L., Casteels M., Vamecq J., Parmentier G., Van Veldhoven P. P., Mannaerts G. P. Beta-oxidation of the carboxyl side chain of prostaglandin E2 in rat liver peroxisomes and mitochondria. J Biol Chem. 1988 Feb 25;263(6):2724–2731. [PubMed] [Google Scholar]
  9. Schinetti M. L., Mazzini A. Effect of l-carnitine on human neutrophil activity. Int J Tissue React. 1986;8(3):199–203. [PubMed] [Google Scholar]
  10. Scholte H. R., Rodrigues Pereira R., Busch H. F., Jennekens F. G., Luyt-Houwen I. E., Vaandrager-Verduin M. H. Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy. Wien Klin Wochenschr. 1989 Jan 6;101(1):12–17. [PubMed] [Google Scholar]
  11. Scholte H. R., Rodrigues Pereira R., de Jonge P. C., Luyt-Houwen I. E., Hedwig M., Verduin M., Ross J. D. Primary carnitine deficiency. J Clin Chem Clin Biochem. 1990 May;28(5):351–357. [PubMed] [Google Scholar]
  12. Wanner C., Riegel W., Schaefer R. M., Hörl W. H. Carnitine and carnitine esters in acute renal failure. Nephrol Dial Transplant. 1989;4(11):951–956. doi: 10.1093/ndt/4.11.951. [DOI] [PubMed] [Google Scholar]
  13. Yamaoka A., Sumimoto H., Isobe R., Minakami S. Formation of leukotriene B4-coenzyme A ester by rat liver microsomes. Biochem Biophys Res Commun. 1988 Aug 15;154(3):1248–1252. doi: 10.1016/0006-291x(88)90273-2. [DOI] [PubMed] [Google Scholar]
  14. Zijlstra F. J., Vincent J. E. Determination of leukotrienes and prostaglandins in [14C] arachidonic acid labelled human lung tissue by high-performance liquid chromatography and radioimmunoassay. J Chromatogr. 1984 Nov 9;311(1):39–50. doi: 10.1016/s0378-4347(00)84689-7. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES