Immunochemical and histopathological evaluation associated with sustained delivery of 5-alpha androstanedione using adult rats as a model.
The specific objective of this study was to evaluate the effect of androstanedione (dihydrotestosterone (DHT)), delivered in a sustained manner by tricalcium phosphate lysine (TCPL) delivery devices, on the biochemical and cytological architecture of reproductive organs using adult rats as a model. A total of twenty four rats were distributed randomly into three equal groups. Rats in group II were implanted (S/C) with empty TCPL devices and served as sham controls. Group III rats were implanted with 1.51 (250 micrograms/day) g/cm3 CDD containing 300 mg DHT each. Group I animals served as unimplanted controls at time zero. Upon sacrifice (6 weeks), the prostatic tissue were collected, fixed, embedded, and sectioned (H&E) by using standard lab protocols. Data analysis of prostatic tissue obtained from rats implanted with such low density TCPL showed microscopic appearance varied somewhat from one area of the gland to another, but generally, there was considerable hyperplasia, as evidenced by accentuation of glandular folds and an increase in the number and size of the epithelial cells, with some areas of the gland showing more severe hyperplasia than others. Meanwhile, cross-sections of prostate obtained from rats implanted with empty CDD were characterized by an essentially normal histological appearance of the gland. These data exemplify the complex interactions which occur between prostate components and exogenous sustained delivery of DHT that are reflected in cell structure and function. Biochemical analysis of the serum revealed that there is remarkable reduction in HDL, and IL 1 (33%). In contrast the level of IL 6 increased (50%) in experimental animals compared to the sham operated animals. In conclusion, this experiment demonstrates that TCPL capsules are capable of delivering supraphysiological doses of DHT in a sustained manner for 6 weeks. The results also reveal that doses of DHT slightly above the physiological level can result in systemic toxicity. In addition, supraphysiological levels of DHT could cause severe BNH and regression to spermatogenesis after 6 weeks in rats, and an increase in the risk factors associated with CVD.
Callender
M
M
University of Mississippi Medical Center, Jackson 39216, USA.
Benghuzzi
H
H
Tucci
M
M
Mohamed
A
A
Cason
Z
Z
Lemos
L
L
Tsao
A
A
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002130:Calcium Phosphates; D002516:Ceramics; D008076:Cholesterol, HDL / Q000097:blood; D004343:Drug Implants; D005043:Etiocholanolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005837:Genitalia, Male / Q000187:drug effects; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008239:Lysine; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001798:Blood Proteins; D002130:Calcium Phosphates; D008076:Cholesterol, HDL; D004343:Drug Implants; D007375:Interleukin-1; D015850:Interleukin-6; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C006576:androstane-3,17-dione; C485838:calcium phosphate, monobasic, anhydrous; D005043:Etiocholanolone; C020243:calcium phosphate; D008239:Lysine; C485829:calcium phosphate, dibasic, anhydrous