D-003 does not possess oestrogenic potential in-vivo: findings of the uterotrophic assay.
D-003 is a mixture of long-chain fatty acids purified from sugarcane wax that inhibits both cholesterol synthesis prior to mevalonate formation, and lipid peroxidation. D-003 has been shown to prevent bone loss and bone resorption in ovariectomized rats, and significantly improves bone resorption markers in postmenopausal women with reduced bone mineral density. As hormone-replacement therapy, D-003 displays cholesterol-lowering and anti-resorptive effects. We have studied its potential oestrogenic activity in-vivo using the uterotrophic assay. Rats were randomly distributed into five groups: a sham-operated group and four groups of ovariectomized rats, one treated with vehicle, one with D-003 (50 mg kg(-1)), one with oestradiol benzoate (30 microg kg(-1)) and one with D-003 (50 mg kg(-1)) plus oestradiol benzoate (30 microg kg(-1)). Treatments were administered for 14 days. Ovariectomy decreased the values of relative uterus weight, epithelium cell height and endometrial thickness compared with sham-operated rats, and these effects were all significantly reduced with oestradiol benzoate, but not with D-003. Concurrent administration of D-003 and oestradiol benzoate had statistically similar effects on all variables as oestradiol benzoate alone. In conclusions, D-003 orally given at 50 mg kg(-1), a dose that prevents bone loss and bone resorption in ovariectomized rats, did not display oestrogenic/anti-oestrogenic activity in-vivo, as assessed in the uterotrophic assay.
Noa
Miriam
M
Center of Natural Products, National Center for Scientific Research, Havana City, Cuba. miriam.noa@cnic.edu.cu
Mendoza
Sarahí
S
Mas
Rosa
R
Gámez
Rafael
R
Valle
Maikel
M
Pardo
Balia
B
Gutiérrez
Ariadne
A
Mendoza
Nilda
N
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; C074283:estradiol 3-benzoate; D004958:Estradiol