Physiological effects following administration of Citrus aurantium for 28days in rats

Toxicology and Applied Pharmacology

Volumn 261, Issue 3, 2012, Pages 236-247

  Hansen, Deborah K ^a   George, Nysia I ^a   White, Gene E ^b   Pellicore, Linda S ^c   Abdel Rahman, Ali ^c   Fabricant, Daniel ^c  

^a NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH   (United States)

^b Toxicologic Pathology Associates   (United States)

^c CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Bitter orange; Blood pressure; Cardiotoxicology; Citrus aurantium; Heart rate; Weight loss

Indexed keywords

CAFFEINE; OXEDRINE; SOUR ORANGE EXTRACT;

ANIMAL EXPERIMENT; ARTICLE; BODY TEMPERATURE; BODY WEIGHT; CONTROLLED STUDY; DIASTOLIC BLOOD PRESSURE; DIET SUPPLEMENTATION; FEMALE; HEART RATE; NONHUMAN; PHYSIOLOGY; QT INTERVAL; RAT; SOUR ORANGE; SURVIVAL RATE; SYSTOLIC BLOOD PRESSURE; TELEMETRY; TREATMENT DURATION;

ANIMALS; BLOOD PRESSURE; BODY TEMPERATURE; BODY WEIGHT; CAFFEINE; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM STIMULANTS; CITRUS; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; PLANT EXTRACTS; RATS; RATS, SPRAGUE-DAWLEY; SURVIVAL; SYNEPHRINE; TELEMETRY; TIME FACTORS; VASOCONSTRICTOR AGENTS;

ANIMALIA; CITRUS AURANTIUM; EPHEDRA; RATTUS;

EID: 84861235722     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2012.04.006     Document Type: Article

References (53)

1. Allison D.B., Cutter G., Poehlman E.T., Moore D.R., Barnes S. Exactly which synephrie alkaloids does Citrus aurantium (bitter orange) contain?. Int. J. Obes. 2005, 29:443-446.
2. Andrews K.W., Schweitzer A., Zhao C., Holden J.M., Roseland J.M., Brandt M., Dwyer J.T., Picciano M.F., Saldanha L.G., Fisher K.D., Yetley E., Betz J.M., Douglass L. The caffeine contents of dietary supplements commonly purchased in the US: analysis of 53 products with caffeine-containing ingredients. Anal. Bioanal. Chem. 2007, 389:231-239.
3. Arbo M.D., Larentis E.R., Linck V.M., Aboy A.L., Pimentel A.L., Henriques A.T., Dallegrave E., Garcia S.C., Leal M.B., Limberger R.P. Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine. Food Chem. Toxicol. 2008, 46:2770-2775.
4. Arbo M.D., Schmitt G.C., Limberger M.F., Charao M.F., Moro A.M., Ribeiro G.L., Dallegrave E., Garcia S.C., Leal M.B., Limberger R.P. Subchronic toxicity of Citrus aurantium L. (Rutaceae) extract and p-synephrine in mice. Regul. Toxicol. Pharmacol. 2009, 54:114-117.
5. Bent S., Padula A., Neuhaus J. Safety and efficacy of Citrus aurantium for weight loss. Am. J. Cardiol. 2004, 94:1359-1361.
6. Blanck H.M., Serdula M.K., Gillespie C., Galuska D.A., Sharpe P.A., Conway J.M., Khan L.K., Ainsworth B.E. Use of nonprescription dietary supplements for weight loss is common among Americans. J. Am. Diet. Assoc. 2007, 107:441-447.
7. Bouchard N.C., Howland M.A., Greller H.A., Hoffman R.S., Nelson L.S. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin. Proc. 2005, 80:541-545.
8. Brown C.M., McGrath J.C., Midgley J.M., Muir A.G.B., O'Brien J.W., Thonoor C.M., Williams C.M., Wilson V.G. Activities of octopamine and synephrine stereoisomers on α-adrenoceptors. Br. J. Pharmacol. 1988, 93:417-429.
9. Bui L.T., Nguyen D.T.T., Ambrose P.J. Blood pressure and heart rate effects following a single dose of bitter orange. Ann. Pharmacother. 2006, 40:53-57.
10. Calapai G., Firenzuoli F., Saitta A., Squadrito F., Arlotta M.R., Costantino G., Inferrera G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Fitoterapia 1999, 70:586-592.
11. 3-adrenoreceptors by octopamine: comparative studies in mammalian fat cells. Naunyn Schmiedeberg's Arch. Pharmacol. 1999, 359:310-321.
12. Colker D.M., Kalman D.S., Torina G.C., Perlis T., Street C. Effects of Citrus aurantium extract, caffeine, and St. John's Wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr. Ther. Res. 1999, 60:145-153.
13. Evans R.L., Siitonen P.H. Determination of caffeine and sympathomimetic alkaloids in weight loss supplements by high-performance liquid chromatography. J. Chromatogr. Sci. 2008, 46:61-67.
14. Fang Y.-S., Shan D.-M., Liu J.-W., Xu W., Li C.-L., Wu H.-Z., Ji G. Effect of constituents from Fructus aurantii immaturus and Radix Paeoniae Alba on gastrointestinal movement. Plant Med. 2009, 75:24-31.
15. Firenzuoli F., Gori L., Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005, 12:247-248.
16. Frary C.D., Johnson R.K., Wang M.Q. Food sources and intakes of caffeine in the diets of persons in the United States. J. Am. Diet. Assoc. 2005, 105:110-113.
17. Fugh-Berman A., Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp. Biol. Med. 2004, 229:698-704.
18. Gange C.A., Madias C., Felix-Getzik E.M., Weintraub A.R., Estes N.A.M. Variant angina associated with bitter orange in a dietary supplement. Mayo Clin. Proc. 2006, 81:545-548.
19. Gray S., Woolf A.D. Citrus aurantium used for weight loss by an adolescent with anorexia nervosa. J. Adolesc. Health 2005, 37:415-416.
20. Haaz S., Fontaine K.R., Cutter G., Limdi N., Perumean-Chaney S., Allison D.B. Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obes. Rev. 2006, 7:79-88.
21. Haller C.A., Benowitz N.L. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N. Engl. J. Med. 2000, 343:1833-1838.
22. Haller C.A., Benowitz N.L., Jacob P. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am. J. Med. 2005, 118:998-1003.
23. Haller C.A., Duan M., Jacob P., Benowitz N. Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. Br. J. Clin. Pharmacol. 2008, 65:833-840.
24. Hamer M. Coffee and health: explaining conflicting results in hypertension. J. Human Hypertens. 2006, 20:909-912.
25. Holmes R.O., Tavee J. Vasospasm and stroke attributable to ephedra-fee Xenadrine: case report. Mil. Med. 2008, 173:708-710.
26. Huang Y.-T., Wang G.-F., Chen C.-F., Chen C.-C., Hong C.-Y., Yang M.C.M. Fructus aurantii reduced portal pressure in portal hypertensive rats. Life Sci. 1995, 57:2011-2020.
27. Ilback N.-G., Siller M., Stalhandske T. Evaluation of cardiovascular effects of caffeine using telemetric monitoring in the conscious rat. Food Chem Toxicol. 2007, 45:834-842.
28. Jordan R., Midgley J.M., Thonoor C.M., Williams C.M. Beta-adrenergic activities of octopamine and synephrine stereoisomers on guinea-pig atria and trachea. J. Pharm. Pharmacol. 1987, 39:752-754.
29. Kalman D.S., Colker C.M., Shi Q., Swain M.A. Effects of a weight-loss aid in healthy overweight adults: double-blind, placebo-controlled clinical trial. Curr. Ther. Res. 2000, 61:199-205.
30. Kalman D., Incledon T., Gaunaurd I., Schwartz H., Krieger D. An acute clinical trial evaluating the cardiovascular effects of an herbal ephedra-caffeine weight loss product in healthy overweight adults. Int. J. Obes. 2002, 26:1363-1366.
31. Kalman D., Incledon T., Gaunaurd I., Shcwartz H., Krieger D. An acute clinical trial evaluating the cardiovascular effects of an herbal ephedra-caffeine weight loss product in healthy overweight adults - correction. Int. J. Obes. 2004, 28:1355-1356.
32. Klontz K.C., Timbo B.B., Street D. Consumption of dietary supplements containing Citrus aurantium (bitter orange) - 2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). Ann. Pharmacother. 2006, 40:1747-1751.
33. Knight C.A., Knight I., Mitchell D.C., Zepp J.E. Beverage caffeine intake in US consumers and subpopulations of interest: estimates from the Share of Intake Panel survey. Food Chem. Toxicol. 2004, 42:1923-1930.
34. Marcus D.M., Grollman A.P. Ephedra-free is not danger-free. Science 2003, 301:1669-1670.
35. Min B., Cios D., Kluger J., White C.M. Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects. Pharmacotherapy 2005, 25:1719-1724.
36. Nasir J.M., Durning S.J., Ferguson M., Barold H.S., Haigney M.C. Exerciseinduced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin. Proc. 2004, 79:1059-1062.
37. Nykamp D.L., Fackih M.N., Compton A.L. Possible association of acute later-wall myocardial infarction and bitter orange supplement. Ann. Pharmacother. 2004, 38:812-816.
38. Pellati F., Benvenuti S. Chromatographic and electrophoretic methods for the analysis of phenetylamine alkaloids in Citrus aurantium. J. Chromatogr. A 2007, 1161:71-88.
39. Penzak S.R., Jann M.W., Cold J.A., Hon Y.Y., Desai H.D., Gurley B.J. Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. J. Clin. Pharmacol. 2001, 41:1059-1063.
40. Pillitteri J.L., Shiffman S., Rohay J.M., Harkins A.M., Surton S.L., Wadden T.A. Use of dietary supplements for weight loss in the United States: results of a national survey. Obesity 2008, 16:790-796.
41. Riksen N.P., Smits P., Rongen G.A. The cardiovascular effects of methylxanthines. Handb. Exp. Pharmacol. 2011, 200:413-437.
42. Rossato L.G., Costa V.M., Limberger R.P., de Lourdes Bastos M. Synephrine: from trace concentrations to massive consumption in weight loss. Food Chem. Toxicol. 2011, 49:8-16.
43. Rossato L.G., Costa V.M., Guedes de Pinho P., Carvalho F., de Lourdes Bastos M., Remiao F. Structural isomerization of synephrine influences its uptake and ensuing glutathione depletion in rat-isolated cardiomyocytes. Arch. Toxicol. 2011, 85:929-939.
44. Sale C., Harris R.C., Delves S., Corbett J. Metabolic and physiological effects of ingesting extracts of bitter orange, green tea and guarana at rest and during treadmill walking in overweight males. Int. J. Obes. 2006, 30:764-773.
45. Santana J., Sharpless K.E., Nelson B.C. Determination of para-synephrine and meta-synephrine positional isomers in bitter orange-containing dietary supplements by LC/UV and LC/MS/MS. Food Chem. 2008, 109:675-682.
46. Sharpe P.A., Granner M.L., Conway J.M., Ainsworth B.E., Dobre M. Availability of weight-loss supplements: results of an audit of retail outlets in a southeastern city. J. Am. Diet. Assoc. 2006, 106:2045-2051.
47. Shekelle P.G., Hardy M.L., Morton S.C., Maglione M., Mojica W.A., Suttorp M.J., Rhodes S.L., Jungvig L., Gagne J. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance. J. Am. Med. Assoc. 2003, 289:1537-1545.
48. Stephensen T.A., Sarlay R. Ventricular fibrillation associated with use of synephrine containing dietary supplement. Mil. Med. 2009, 174:1313-1319.
49. Stohs S.J., Preuss H.G., Shara M. The safety of Citrus aurantium (Bitter Orange) and its primary protoalkaloide p-synephrine. Phytother. Res. 2011, 25:1421-1428.
50. Stohs S.J., Preuss H.G., Shara M. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects. Oxid. Med. Cell Longev. 2011, 10.1155/2011/482973.
51. Sultan S., Spector J., Mitchell R.M. Ischemic colitis associated with use of a bitter orange-containing dietary weight-loss supplement. Mayo Clin. Proc. 2006, 81:1630-1631.
52. Thomas J.E., Munir J.A., McIntyre P.Z., Ferguson M.A. STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement. A case report and review of the literature. Tex. Heart Inst. J. 2009, 36:586-590.
53. Westfall T.C., Westfall D.P. Chapter 10. Adrenergic agonists and antagonists. Goodman and Gilman's Pharmacological Basis of Therapeutics 2006, 237-296. McGraw-Hill Co. 11th edition. L. Brunton, B. Chabner, B. Knollmann (Eds.).