Effects of oral androstenedione on phospholipid fatty acids, ATP, caspase-3, prostaglandin E(2) and C-reactive protein in serum and livers of pregnant and non-pregnant female rats.
Androstenedione, a steroidal dietary supplement taken to enhance athletic performance, could affect serum and liver lipid metabolism, induce liver toxicity or alter inflammatory response depending on dose and duration of exposure. Pregnancy could further exaggerate these effects. To examine this, mature female rats were gavaged with 0, 5, 30 or 60 mg/kg/day androstenedione beginning two weeks prior to mating and continuing through gestation day 19. Non-pregnant female rats were gavaged over the same time frame with 0 or 60 mg/kg/day androstenedione. Serum was collected and livers were removed from dams on gestation day 20 and from non-pregnant rats after 5 weeks of treatment. Androstenedione had no effect on serum total cholesterol, triglycerides or HDL-cholesterol, but significantly decreased C-reactive protein in pregnant rats and prostaglandin E(2) in serum of both pregnant and non-pregnant rats. There were treatment related decreases in liver ATP and, to a lesser degree, caspase-3 and no change in alkaline phosphatase of pregnant female rats. Androstenedione decreased docosahexaenoic acid in both serum and liver phospholipids of pregnant female rats. In conclusion, oral androstenedione did not result in overt hepatotoxicity in pregnant female rats, but produced modest changes in lipid metabolism and may impair regeneration of injured hepatic cells or tissue.
Wiesenfeld
P W
PW
US FDA, Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, 8301 Muirkirk Road, Laurel, MD 20708, USA. pweisenf@cfsan.fda.gov
Sapienza
P P
PP
Flynn
T J
TJ
Ford
C E
CE
Ross
I A
IA
Sahu
S
S
Kim
C S
CS
O'Donnell
M W
MW
Collins
T F X
TF
Sprando
R L
RL
D000255:Adenosine Triphosphate / Q000097:blood / Q000378:metabolism; D000284:Administration, Oral; D000735:Androstenedione / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D051381:Rats
D005227:Fatty Acids; D000735:Androstenedione; D000255:Adenosine Triphosphate; D002097:C-Reactive Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D015232:Dinoprostone