Letter to Editor
Year 2017,
Volume: 64 Issue: 2, 103 - 110, 01.06.2017
Abstract
CDP-choline is an endogen molecule and also a drug that is used in several trauma and ischemic conditions. It has been demonstrated that it improves the hemodynamic parameters in different shock models and prevents tissue damage in rats. The current study tested the effect of CDP-choline on hypotension, inflammation and tissue injury induced by septic shock model in rats. Twenty-four adult, male Spraque-Dawley rats, weighing 250-300 g were used. Septic shock was induced by cecal ligation-incision (CLI). CDP-choline (100 mg/kg) injected intravenously (i.v.) at the 180th minute of the experiment. The animals were observed for 180 minutes after the injection, then blood and tissue samples were obtained for cytokine measurements and histological examinations, respectively. The cecal ligation-incision decreased arterial pressure and increased heart rate. Intravenous injection of CDP-choline reversed hypotension and increased arterial pressure up to control levels within the first 60 minutes without changing the increase in heart rate. The effect lasted for 3 hours. CDP-choline attenuated the increases in TNF-α, IL-1β and IL-6 levels in septic shock. Moreover, the drug exerted protective effects for the injury induced by septic shock in lungs, liver and kidney tissues; whereas this effect was not present on spleen. In conclusion, the present data suggested that intravenous CDP-choline administration can improve the deteriorations in hemodynamic and inflammatory parameters and can prevent the tissue injury in septic shock-induced by CLI in rats
References
- Adibhatla RM, Hatcher JF (2002): Citicoline mechanisms and clinical efficacy in cerebral ischemia. J Neurosci Res, 70, 133-139.
- Adibhatla RM, Hatcher JF (2005): Cytidine 5’- diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res, 30, 15-23.
- Adibhatla RM, Hatcher JF, Dempsey RJ (2001): Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke, 32, 2376-2381.
- Adibhatla RM, Hatcher JF, Dempsey RJ (2004): Cytidine-5'-diphosphocholine (CDP-choline) affects CTP: Phosphocholine phosphatidylcholine after transient brain ischemia. J Neurosci Res, 76, 390-396. and lyso
- Ahmad A, Druzhyna N, Szabo C (2016): Delayed treatment with sodium hydrosulfide improves regional blood flow and alleviates cecal ligation and puncture (CLP)-induced septic shock. Shock, Epub ahead of print (doi: 10.1097/SHK.0000000000000589)
- Alkondon M, Pereira EF, Barbosa CT, et al. (1997): Neuronal nicotinic acetylcholine receptor activation modulates gamma-aminobutyric acid release from CA1 neurons of rat hippocampal slices. J Pharmacol Exp Ther, 283, 1396-1411.
- Blusztajn JK, Wurtman RJ (1983): Choline and cholinergic neurons. Science, 22, 614-620.
- Borovikova LV, Ivanova S, Zhang M, et al. (2000): Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 405, 458-462.
- Cavun S, Savci V (2004): CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: The cholinergic involvement. Fundam Clin Pharmacol, 18, 513-523.
- Cavun S, Savci V, Ulus IH (2004): Centrally injected CDP-choline increases plasma vasopressin levels by central cholinergic activation. Fundam Clin Pharmacol, 18, 71-77.
- Coskun C, Avci B, Ocak N, et al. (2010): Effect of repeatedly given CDP-choline on cardiovascular and tissue injury in spinal shock conditions: Investigation of the acute phase. J Pharm Pharmacol, 62, 497-506.
- Coskun C, Avci B, Yalcin M, et al. (2014): Protective effect of CDP-choline on ischemia-reperfusion-induced myocardial tissue injury in rats. Ir J Med Sci, 183, 539-548.
- Deitch EA (1998): Animal models of sepsis and shock: A review and lessons learned. Shock, 9, 1-11.
- Dorman RV, Dabrowiecki Z, Horrocks LA (1983): Effects of CDP-choline and CDP-ethanolamine on the alterations in rat brain lipid metabolism induced by global ischemia. J Neurochem, 40, 276-279. 15. Downing JEG, Miyan JA (2000): Neural immunoregulation: Emerging roles for nerves in immune homeostasis and disease. Immunol Today, 21, 281-289.
- Esmon CT (2004): Why do animal models (sometimes) fail to mimic human sepsis? Crit Care Med, 32, 219-222.
- Fiedorowicz M, Makarewicz D, Stan´czak-Mrozek KI, et al. (2008): CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp, 68, 389-397.
- G-Coviella IL, Wurtman RJ (1992): Enhancement by cytidine of Neurochem, 59, 338-343. phospholipids synthesis. J
- Hotchkiss RS, Karl IE (2003): The pathophysiology and treatment of sepsis. N Engl J Med, 348, 138.
- Ilcol YO, Gurun MS, Taga Y, et al. (2003): Choline increases intraperitoneally and augments basal and stimulated acetylcholine release from the rat minced pancreas in vitro. Eur J Biochem, 270, 991-999. in rat when injected
- Ilcol YO, Yilmaz Z, Cansev M, et al. (2009): Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: Involvement of the peripheral nicotinic acetylcholine receptors. Shock, 32, 286-294.
- Klein J (2000): Membrane breakdown in acute and chronic neurodegeneration: phospholipids. J Neural Transm, 107, 1027-1063. on choline-containing
- Li XD, Buccafusco JJ (2004): Role of alpha7 nicotinic acetylcholine receptors in the pressor response to intracerebroventricular injection of choline: Blockade by amyloid peptide Abeta1-42. J Pharmacol Exp Ther, 309, 1206-1212.
- Marshall JC, Vincent JL, Fink MP, et al. (2003): Measures, markers, and mediators: toward a staging system for clinical sepsis. A report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25-26, 2000. Crit Care Med, 31, 1560-1567.
- Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, et al. (2008): Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Mol Med, 14, 567-574.
- Pavlov VA, Ochani M, Yang LH, et al. (2007): Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med, 35, 1139-1144.
- Rao AM, Hatcher JF, Dempsey RJ (2000): Lipid alterations in transient forebrain ischemia: Possible new mechanisms Neurochem, 75, 2528-2535. neuroprotection. J
- Rao AM, Hatcher JF, Dempsey RJ (2001): Does CDP- choline modulate phospholipase activities after transient forebrain ischemia? Brain Res, 893, 268-272.
- Riedemann NC, Guo RF, Ward PA (2003): Novel strategies for the treatment of sepsis. Nat Med, 9, 517-524.
- Rivera CA, Wheeler MD, Enomoto N, et al. (1998): A choline rich diet improves survival in a rat model of endotoxin shock. Am J Physiol, 275, 862-867.
- Savci V, Cavun S, Goktalay G, et al. (2002): Cardiovascular effects of intracerebroventricularly injected CDP-choline in normotensive and hypotensive animals: The Schmiedebergs Arch Pharmacol, 365, 388-398. system. Naunyn
- Savci V, Goktalay G, Cansev M, et al. (2003): Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: Effect is mediated by central cholinergic activation. Eur J Pharmacol, 468, 129-139. 33. Savci V, Intracerebroventricular vasopressin and augments plasma vasopressin response to osmotic stimulation and hemorrhage. Brain Res, 942, 58- 70. G, choline plasma increases
- Savci V, Ulus IH (1997): Cardiovascular effects of central choline during endotoxin shock in the rat. J Cardiovasc Pharmacol, 30, 667-675.
- Savci V, Wurtman RJ (1995): Effect of cytidine on membrane phospholipid synthesis in rat striatal slices. J Neurochem, 64, 378-384.
- Secades JJ (2011): Citicoline: Pharmacological and clinical review, 2010 update. Rev Neurol, 52, 1-62.
- Stoll AL, Renshaw PF, DeMicheli E, et al. (1995): Choline ingestion increases the resonance of choline containing compound in human brain: An in vivo proton magnetic resonance study. Biol Psych, 37, 170-174.
- Ulus IH, Wurtman RJ, Mauron C, et al. (1995): Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res, 484, 217-227.
- Wang H, Yu M, Ochani M, et al. (2003): Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature, 421, 384-388.
- Wang H, Liao H, Ochani M, et al. (2004): Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med, 10, 1216-1221.
- Weiss GB (1995): Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci, 56, 637-660.
- Wenzel RP, Edmond MB (2012): Septic shock devaluating another failed treatment. N Engl J Med, 366, 2122.
- Wijdicks EF, Stevens M (1992): The role of hypotension in septic encephalopathy following surgical procedures. Arch Neurol, 49, 653.
- Wurtman RJ (1992): Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci, 15, 117-122.
- Yilmaz MS, Coskun C, Yalcın M, et al. (2008): CDP- choline prevents cardiac arrhythmias and lethality induced by short-term myocardial ischemia-reperfusion injury in the rat: involvement of central muscarinic cholinergic mechanisms. Naunyn Schmiedebergs Arch Pharmacol, 378, 293-301.
- Yilmaz Z, Ilcol YO, Torun S, et al. (2006): Intravenous administration of choline or cdp-choline improves platelet count and platelet closure times in endotoxin-treated dogs. Shock, 25, 73-79.
Year 2017,
Volume: 64 Issue: 2, 103 - 110, 01.06.2017
Abstract
CDP-kolin, endojen bir molekül olmasının yanısıra travma ve iskemik koşullarda da kullanılan bir ilaçtır. Değişik şok modellerinde, sıçanlarda hemodinamik parametreleri iyileştirdiği ve doku hasarına karşı koruyucu etki gösterdiği ortaya konmuştur. Bu çalışmada, CDP-kolin’in sıçanlarda septik şokun neden olduğu hipotansiyon, inflamasyon ve doku hasarı üzerine olan etkileri incelendi. Deneylerde, ağırlıkları 250-300 g arasında değiş en 24 adet Spraque-Dawley ırkı erkek sıçan kullanıldı. Septik şok modeli oluşturmak için çekal bağlama-kesme yöntemi uygulandı. CDP-kolin (100 mg/kg), deneyin 180. dakikasında intravenöz (i.v.) olarak uygulandı. Hayvanlar enjeksiyon sonrası 180 dakika daha gözlendikten sonra sitokin ölçümleri ve histolojik incelemeler için sırasıyla kan ve doku örnekleri toplandı. Çekal bağlama-kesme kan basıncını azaltırken kalp atım sayısını artırdı. İntravenöz CDP-kolin uygulaması hipotansiyonu düzeltti ve arteryel basıncı ilk 60 dakika içerisinde, kalp hızındaki yüksekliği değiştirmeden, kontrol düzeylerine kadar artırdı. Etki 3 saat kadar sürdü. CDP-kolin, septik şoktaki TNF-α, IL-1β ve IL-6 düzeylerindeki yükselmeleri de azalttı. Bu etkilere ek olarak ilaç; akciğer, karaciğer ve böbreklerde (ancak dalakta değil) septik şokun sebep olduğu hasara karşı koruyucu etki gösterdi. Sonuç olarak mevcut veriler intravenöz CDP-kolin uygulamasının; çekal bağlama-kesme ile oluşturulan septik şokun neden olduğu hemodinamik ve inflamatuar parametrelerdeki bozukluklarda iyileşmeye ve meydana gelen doku hasarına karşı koruyucu olduğunu ortaya koymaktadır
Keywords
References
- Adibhatla RM, Hatcher JF (2002): Citicoline mechanisms and clinical efficacy in cerebral ischemia. J Neurosci Res, 70, 133-139.
- Adibhatla RM, Hatcher JF (2005): Cytidine 5’- diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res, 30, 15-23.
- Adibhatla RM, Hatcher JF, Dempsey RJ (2001): Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke, 32, 2376-2381.
- Adibhatla RM, Hatcher JF, Dempsey RJ (2004): Cytidine-5'-diphosphocholine (CDP-choline) affects CTP: Phosphocholine phosphatidylcholine after transient brain ischemia. J Neurosci Res, 76, 390-396. and lyso
- Ahmad A, Druzhyna N, Szabo C (2016): Delayed treatment with sodium hydrosulfide improves regional blood flow and alleviates cecal ligation and puncture (CLP)-induced septic shock. Shock, Epub ahead of print (doi: 10.1097/SHK.0000000000000589)
- Alkondon M, Pereira EF, Barbosa CT, et al. (1997): Neuronal nicotinic acetylcholine receptor activation modulates gamma-aminobutyric acid release from CA1 neurons of rat hippocampal slices. J Pharmacol Exp Ther, 283, 1396-1411.
- Blusztajn JK, Wurtman RJ (1983): Choline and cholinergic neurons. Science, 22, 614-620.
- Borovikova LV, Ivanova S, Zhang M, et al. (2000): Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 405, 458-462.
- Cavun S, Savci V (2004): CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: The cholinergic involvement. Fundam Clin Pharmacol, 18, 513-523.
- Cavun S, Savci V, Ulus IH (2004): Centrally injected CDP-choline increases plasma vasopressin levels by central cholinergic activation. Fundam Clin Pharmacol, 18, 71-77.
- Coskun C, Avci B, Ocak N, et al. (2010): Effect of repeatedly given CDP-choline on cardiovascular and tissue injury in spinal shock conditions: Investigation of the acute phase. J Pharm Pharmacol, 62, 497-506.
- Coskun C, Avci B, Yalcin M, et al. (2014): Protective effect of CDP-choline on ischemia-reperfusion-induced myocardial tissue injury in rats. Ir J Med Sci, 183, 539-548.
- Deitch EA (1998): Animal models of sepsis and shock: A review and lessons learned. Shock, 9, 1-11.
- Dorman RV, Dabrowiecki Z, Horrocks LA (1983): Effects of CDP-choline and CDP-ethanolamine on the alterations in rat brain lipid metabolism induced by global ischemia. J Neurochem, 40, 276-279. 15. Downing JEG, Miyan JA (2000): Neural immunoregulation: Emerging roles for nerves in immune homeostasis and disease. Immunol Today, 21, 281-289.
- Esmon CT (2004): Why do animal models (sometimes) fail to mimic human sepsis? Crit Care Med, 32, 219-222.
- Fiedorowicz M, Makarewicz D, Stan´czak-Mrozek KI, et al. (2008): CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. Acta Neurobiol Exp, 68, 389-397.
- G-Coviella IL, Wurtman RJ (1992): Enhancement by cytidine of Neurochem, 59, 338-343. phospholipids synthesis. J
- Hotchkiss RS, Karl IE (2003): The pathophysiology and treatment of sepsis. N Engl J Med, 348, 138.
- Ilcol YO, Gurun MS, Taga Y, et al. (2003): Choline increases intraperitoneally and augments basal and stimulated acetylcholine release from the rat minced pancreas in vitro. Eur J Biochem, 270, 991-999. in rat when injected
- Ilcol YO, Yilmaz Z, Cansev M, et al. (2009): Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: Involvement of the peripheral nicotinic acetylcholine receptors. Shock, 32, 286-294.
- Klein J (2000): Membrane breakdown in acute and chronic neurodegeneration: phospholipids. J Neural Transm, 107, 1027-1063. on choline-containing
- Li XD, Buccafusco JJ (2004): Role of alpha7 nicotinic acetylcholine receptors in the pressor response to intracerebroventricular injection of choline: Blockade by amyloid peptide Abeta1-42. J Pharmacol Exp Ther, 309, 1206-1212.
- Marshall JC, Vincent JL, Fink MP, et al. (2003): Measures, markers, and mediators: toward a staging system for clinical sepsis. A report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25-26, 2000. Crit Care Med, 31, 1560-1567.
- Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, et al. (2008): Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Mol Med, 14, 567-574.
- Pavlov VA, Ochani M, Yang LH, et al. (2007): Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med, 35, 1139-1144.
- Rao AM, Hatcher JF, Dempsey RJ (2000): Lipid alterations in transient forebrain ischemia: Possible new mechanisms Neurochem, 75, 2528-2535. neuroprotection. J
- Rao AM, Hatcher JF, Dempsey RJ (2001): Does CDP- choline modulate phospholipase activities after transient forebrain ischemia? Brain Res, 893, 268-272.
- Riedemann NC, Guo RF, Ward PA (2003): Novel strategies for the treatment of sepsis. Nat Med, 9, 517-524.
- Rivera CA, Wheeler MD, Enomoto N, et al. (1998): A choline rich diet improves survival in a rat model of endotoxin shock. Am J Physiol, 275, 862-867.
- Savci V, Cavun S, Goktalay G, et al. (2002): Cardiovascular effects of intracerebroventricularly injected CDP-choline in normotensive and hypotensive animals: The Schmiedebergs Arch Pharmacol, 365, 388-398. system. Naunyn
- Savci V, Goktalay G, Cansev M, et al. (2003): Intravenously injected CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock: Effect is mediated by central cholinergic activation. Eur J Pharmacol, 468, 129-139. 33. Savci V, Intracerebroventricular vasopressin and augments plasma vasopressin response to osmotic stimulation and hemorrhage. Brain Res, 942, 58- 70. G, choline plasma increases
- Savci V, Ulus IH (1997): Cardiovascular effects of central choline during endotoxin shock in the rat. J Cardiovasc Pharmacol, 30, 667-675.
- Savci V, Wurtman RJ (1995): Effect of cytidine on membrane phospholipid synthesis in rat striatal slices. J Neurochem, 64, 378-384.
- Secades JJ (2011): Citicoline: Pharmacological and clinical review, 2010 update. Rev Neurol, 52, 1-62.
- Stoll AL, Renshaw PF, DeMicheli E, et al. (1995): Choline ingestion increases the resonance of choline containing compound in human brain: An in vivo proton magnetic resonance study. Biol Psych, 37, 170-174.
- Ulus IH, Wurtman RJ, Mauron C, et al. (1995): Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res, 484, 217-227.
- Wang H, Yu M, Ochani M, et al. (2003): Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature, 421, 384-388.
- Wang H, Liao H, Ochani M, et al. (2004): Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med, 10, 1216-1221.
- Weiss GB (1995): Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci, 56, 637-660.
- Wenzel RP, Edmond MB (2012): Septic shock devaluating another failed treatment. N Engl J Med, 366, 2122.
- Wijdicks EF, Stevens M (1992): The role of hypotension in septic encephalopathy following surgical procedures. Arch Neurol, 49, 653.
- Wurtman RJ (1992): Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci, 15, 117-122.
- Yilmaz MS, Coskun C, Yalcın M, et al. (2008): CDP- choline prevents cardiac arrhythmias and lethality induced by short-term myocardial ischemia-reperfusion injury in the rat: involvement of central muscarinic cholinergic mechanisms. Naunyn Schmiedebergs Arch Pharmacol, 378, 293-301.
- Yilmaz Z, Ilcol YO, Torun S, et al. (2006): Intravenous administration of choline or cdp-choline improves platelet count and platelet closure times in endotoxin-treated dogs. Shock, 25, 73-79.
There are 44 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Surgery |
| Other ID | JA68RD27RC |
| Journal Section | Research Article |
| Authors | |
| Publication Date | June 1, 2017 |
| Published in Issue | Year 2017Volume: 64 Issue: 2 |