Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 2: metabolic and hormonal changes.
The present study describes the metabolic changes observed in a dietary subacute toxicity experiment with the ergot alkaloid alpha-ergocryptine in Sprague-Dawley rats. The observed effects on metabolic and hormonal parameters were described separately from the general toxicological effects, in view of the important role of dopamine agonists in metabolism (e.g. ergot alkaloids in fescue toxicosis). The rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). Total cholesterol and high-density lipoprotein (HDL)-cholesterol were decreased dose dependently in females but the ratio HDL-cholesterol/total cholesterol was only decreased at 20 mg/kg body weight. Triglycerides and glucose concentrations were decreased in the highest dose groups of both sexes. Serum urea concentrations were increased in the 20, 100 and 500 mg/kg dose groups. Insulin, glucagon and liver glycogen were increased in the highest dose group at the end of the study, when the animals were allowed to eat prior to blood sampling and necropsy. Prolactin, T4 and FT4 were decreased in the 20, 100 and 500 mg/kg dose groups of both sexes. Follicle-stimulating hormone (FSH) was decreased in the 20, 100 and 500 mg/kg female dose groups and luteinizing hormone (LH) was increased in the 20, 100 and 500 mg/kg male dose groups. It is postulated that the observed effects on food intake, metabolism (lipid and carbohydrate) and hormonal parameters are due to an interaction of ergocryptine with central dopaminergic activities, which comprise a major functional component of a central regulatory system for metabolism.
Janssen
G B
GB
Centre Substances and Risk Assessment, National Institute of Public Health and the Environment, 3720 BA Bilhoven, The Netherlands.
Beems
R B
RB
Elvers
L H
LH
Speijers
G J
GJ
D000818:Animals; D001786:Blood Glucose; D008076:Cholesterol, HDL / Q000097:blood; D018491:Dopamine Agonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005934:Glucagon / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006728:Hormones / Q000502:physiology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D018491:Dopamine Agonists; D004873:Ergolines; D006728:Hormones; D007328:Insulin; D014280:Triglycerides; C100269:ergocryptine; D014508:Urea; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006003:Glycogen; D005934:Glucagon; D013974:Thyroxine