Dose dependency and reversibility of serotonin-induced valvular heart disease in rats.
Serotonergic drugs may lead to valvular heart disease in humans and more recently also in rats. Although clinical data suggest that dose dependency and reversibility after drug cessation might occur, proof of this is lacking. For that purpose, a total of 106 rats were prospectively enrolled: 22 control animals and 7 groups of 12 rats that received daily subcutaneous serotonin injections (5, 10, 20, 30, 40, 50 and 60 mg/kg respectively) for 12 weeks. At 12 weeks, half of the animals of each group were killed for histological analysis, whereas the remaining rats were further followed (without serotonin injections) for an additional 8 weeks. After 12 weeks of serotonin treatment, aortic and mitral regurgitation (AR, MR) were more frequently observed in the high dose groups (>30 mg/kg) compared to controls. Moreover, aortic and mitral valves were also thicker in the high dose groups compared to controls. After 8 weeks free of serotonin injections, AR and MR were no longer significantly higher than controls. Moreover, aortic and mitral valve thickness had normalized, returning to control levels. In conclusion, this study provides evidence for a dose-dependent valvular toxicity of serotonergic drugs, which appears to be reversible after drug withdrawal.
Droogmans
Steven
S
Department of Cardiology, UZ Brussel, 1090 Jette, Belgium. steven_droogmans@yahoo.com
Roosens
Bram
B
Cosyns
Bernard
B
Degaillier
Céline
C
Hernot
Sophie
S
Weytjens
Caroline
C
Garbar
Christian
C
Caveliers
Vicky
V
Pipeleers-Marichal
Miriam
M
Franken
Philippe R
PR
Bossuyt
Axel
A
Schoors
Danny
D
Lahoutte
Tony
T
Van Camp
Guy
G
D000818:Animals; D001021:Aortic Valve / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006349:Heart Valve Diseases / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D008943:Mitral Valve / Q000187:drug effects / Q000473:pathology; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D012075:Remission, Spontaneous; D012701:Serotonin / Q000008:administration & dosage* / Q000633:toxicity*; D013997:Time Factors
D012701:Serotonin