Research Journal of Pharmacology and Pharmacodynamics

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Novel Approaches in Erythropoietin: A Review


Affiliations
1 Department of Pharmacology, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana- 384001, Gujarat, India
     

   Subscribe/Renew Journal


Erythropoietin, or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. Also called hematopoietin or hemopoietin, it is produced by the peritubular capillary endothelial cells in the kidney, and is the hormone that regulates red blood cell production. The existence of a hormone that controls RBC production was first suggested by the experiments of Paul Carnot in 1906, who created anemic rabbits and then transfused their serum into recipient rabbits. EPO is produced by peritubular cells in the adult kidney, and in hepatocytes in the fetus. In adults, a small amount is also produced by the liver. The rate of Epo synthesis and secretion depends on local oxygen concentrations; hypoxia is the main stimulus for Epo production. Although the use of erythropoietin has been studied in critically ill patients, erythropoietin has not been shown to be effectice in this setting. In a randomized controlled trial, erythropoietin insignificantly reduced mortality among critically ill patients. In 1983, the gene coding for EPO was identified, leading to its synthesis as epoetin-alfa by American genetic research corporation, Amgen, who patented the drug under the name Epogen. In 1989, another company, Ortho Biotech, a subsidiary of Johnson and Johnson, began marketing the drug under license as Procrit in the US, and Eprex in the rest of the world.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Siren AL et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA(2001); 98: 4044-4049.

  • Haroon ZA, Amin K, Jiang X, Arcasoy MO. A novel role for erythropoietin during fibrin induced wound healing response. Am. J. Pathol. (September 2003) ;163(3): 993- 1000.

  • Miyake T, Kung CK, Goldwasser E. Purification of human erythropoietin.j Biol Chem1977;252:5558-5564.

  • Lin FK, Suggs S, Lin CH, et al., Cloning and expression of the human erythropoietin gene. Am. J. Pathol 1985;82: 7580-7584.

  • Browne JK et al.Erythropoietin: gene cloning, protein structure, and biological properties. Cold Spring Harb Symp Quant Biol.(1986); 51:693-702.

  • Eschbach JW, Kelly MR, Haley NR, Abels RI, Adamson JW. "Treatment of the anemia of progressive renal failure with recombinant human erythropoietin". N. Engl. J. Med. 1989; 321 (3): 158-63.

  • Singh AK, Szczech L, Tang KL, et al.Correction of anemia with epoetin alfa in chronic kidney disease. N. Engl. J. Med. 2006;355 (20): 2085-98.

  • Macdougall IC, Tucker B, Thompson J, Tomson CR, Baker LR, Raine AE.A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int. 1996;50 (5): 1694-9.

  • Tonelli M, Hemmelgarn B, Reiman T, et al.Benefits and harms Of erythropoiesis stimulating agents for anemia related to cancer; a meta analysis. CMAJ May 2009;180 (11): E62-71.

  • Corwin HL, Gettinger A, Fabian TC, et al.Efficacy and safety of epoetin alfa in critically ill patients. N. Engl. J. Med. 2007; 357 (10): 965-76.

  • Zarychanski R, Turgeon AF, McIntyre L, Fergusson DA.Erythropoietin-receptor agonists in critically ill patients: a meta-analysis of randomized controlled trials. CMAJ : Canadian Medical Association journal 2007;177 (7): 725- 34.

  • Parisotto R, Wu M, Ashenden MJ, et al.Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica 2001;86 (2): 128-37.

  • Drüeke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A.Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N. Engl. J. Med. 2006; 355 (20): 2071-84.

  • FDA Public Health Advisory; Erythropoiesis Stimulating Agents (ESAs): Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp). Retrieved on 2007-06-05.

  • Dr. bharat shah. Indian best practicies guidelines ;2003;3:125-127.

  • FDA Briefing Document: Safety Concerns Associated with Aranesp (darbepoetin alfa) Amgen, Inc. and Procrit (epoetin alfa) Ortho Biotech, L.P., for the Treatment of Anemia Associated with Cancer Chemotherapy. May 4, 2004;130- 145.

  • Jelkmann W.Erythropoietin after a century of research: younger than ever. European journal of haematology March 2007;78 (3): 183-205.

  • Spinowitz et al. types of erythropoietin.Curr Med Res Opin2006; 22:2507-13.

  • Bahlmann FH Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin. Kidney Int 2003; 64: 1648-1652

  • Skibeli V, Nissen-Lie G, Torjesen P. Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin. Blood. 2001 Dec;98(13):3626-34.

  • Jermy levy,julie morgan;Oxford handbook of dialysis, 2004;2:620-650.

  • De Santo NG, Cirillo M, Kirsch KA, et al. Anemia and erythropoietin in space flights. Semin Nephrol. 2005 Nov;25(6):379-87.

  • Percy MJ, Furlow PW, Lucas GS, et al. A gain-of-function mutation in the HIF2A gene in familial erythrocytosis.N Engl J Med. 2008 Jan;358(2):162-8.


Abstract Views: 250

PDF Views: 1




  • Novel Approaches in Erythropoietin: A Review

Abstract Views: 250  |  PDF Views: 1

Authors

Angad J. Nayak
Department of Pharmacology, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana- 384001, Gujarat, India
I. S. Anand
Department of Pharmacology, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana- 384001, Gujarat, India
C. N. Patel
Department of Pharmacology, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana- 384001, Gujarat, India

Abstract


Erythropoietin, or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. Also called hematopoietin or hemopoietin, it is produced by the peritubular capillary endothelial cells in the kidney, and is the hormone that regulates red blood cell production. The existence of a hormone that controls RBC production was first suggested by the experiments of Paul Carnot in 1906, who created anemic rabbits and then transfused their serum into recipient rabbits. EPO is produced by peritubular cells in the adult kidney, and in hepatocytes in the fetus. In adults, a small amount is also produced by the liver. The rate of Epo synthesis and secretion depends on local oxygen concentrations; hypoxia is the main stimulus for Epo production. Although the use of erythropoietin has been studied in critically ill patients, erythropoietin has not been shown to be effectice in this setting. In a randomized controlled trial, erythropoietin insignificantly reduced mortality among critically ill patients. In 1983, the gene coding for EPO was identified, leading to its synthesis as epoetin-alfa by American genetic research corporation, Amgen, who patented the drug under the name Epogen. In 1989, another company, Ortho Biotech, a subsidiary of Johnson and Johnson, began marketing the drug under license as Procrit in the US, and Eprex in the rest of the world.

References