title: Cardiovascular toxicity of Citrus aurantium in exercised rats.
abstract: When safety concerns forced the removal of ephedra from the market, other botanicals, including Citrus aurantium or bitter orange (BO) were used as replacements. A major component of the BO extract is synephrine, a chemical that is structurally similar to ephedrine. Because ephedrine has cardiovascular effects that may be exacerbated during physical exercise, the purpose of this study was to determine whether extracts containing synephrine produced adverse effects on the cardiovascular system in exercising rats. Sprague-Dawley rats were dosed daily by gavage for 28 days with 10 or 50 mg of synephrine/kg body weight from one of two different extracts; caffeine was added to some doses. The rats ran on a treadmill for 30 min/day, 3 days/week. Heart rate, blood pressure, body temperature, and QT interval were monitored. Both doses of both extracts significantly increased systolic and diastolic blood pressure for up to 8 h after dosing. Effects on heart rate and body temperature appeared to be due primarily to the effects of caffeine. These data suggest that the combination of synephrine, caffeine, and exercise can have significant effects on blood pressure and do not appear to be effective in decreasing food consumption or body weight.
authors: Division of Systems Biology, Food and Drug Administration (FDA)/NCTR, 3900 NCTR Rd., Jefferson, AR, 72079, USA, deborah.hansen@fda.hhs.gov.
authors: Deborah K
authors: DK
authors: Hansen
authors: Nysia I
authors: NI
authors: George
authors: Gene E
authors: GE
authors: White
authors: Ali
authors: A
authors: Abdel-Rahman
authors: Linda S
authors: LS
authors: Pellicore
authors: Daniel
authors: D
authors: Fabricant
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002110:Caffeine / Q000633:toxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000633:toxicity; D002957:Citrus / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D023381:Endpoint Determination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010936:Plant Extracts / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D013566:Sympathomimetics / Q000633:toxicity; D013578:Synephrine / Q000633:toxicity
chemical_list: D000697:Central Nervous System Stimulants; D010936:Plant Extracts; D013566:Sympathomimetics; D002110:Caffeine; D013578:Synephrine