Histomorphometric evaluation of renal glomeruli exposed to sustained delivery of estrogen using adult ovariectomized rats.
Hormonal replacement therapy (HRT) has shown to be efficacious in treatment and preventing of heart disease, osteoporosis and reducing mortality in postmenopausal and ovariectomized females. Several attempts to utilize the native estrogen and its analogs such as Depo-Provera, conjugated estrogen and estrogen benzoate have shown different physiological responses. In addition, the route of administration and its mode of action is lacking in the literature. The specific objective of this study was to investigate the role of sustained delivery of estrogen on the functional and structural capacity of the kidney using adult female rats as a model. A total of 24 adult female rats were subdivided into four equal groups. Groups I and II were ovariectomized (OVX) by following standard laboratory surgical procedures. Each rat in groups II and III (intact) were implanted with tricalcium phosphate lysine (TCPL) drug delivery system loaded with 40 mg of estrogen. Rats in group IV were unimplanted and untreated to be served as a control group. At the end of 45 days post treatment the animals were sacrificed by using overdose of Halothane and assured by cervical dislocation. Vital and reproductive organs were retrieved, weighed and subjected to H&E staining procedure. The results of this investigation suggest: (i) TCPL delivery system released estrogen at a sustained level for 45 days without any untoward response, (ii) the wet weights of kidneys (normalized to body weight) were increased (p < 0.05) in intact rats treated with estrogen compared to control, (iii) sustained delivery of estrogen resulted in a maintenance of kidney weights compared to the control level, however, the lack of estrogen treatment resulted in a remarkable regression in the kidney weights of OVX rats, (iv) the ratio of renal arteries-diameter (normalized to arterial wall thickness) was significantly increased in intact rats treated with estrogen compared to the control and other experimental groups, (v) histopathological evolutions of renal tubules revealed tubular epithelial damage in intact rats received estrogen treatment compared to the control and other groups. In conclusion, this study suggests that exogenous estrogen therapy could lead profound tubular damage and consequently major renal insufficiency. HRT also could lead to hypertensive renal damage.
Department of Pathology, Health Sciences, and Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS, USA.
Naiel A
NA
Hafez
Hamed
H
Benghuzzi
Michelle
M
Tucci
D000818:Animals; D001835:Body Weight; D002130:Calcium Phosphates; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology; D012680:Sensitivity and Specificity
D002130:Calcium Phosphates; D004343:Drug Implants; D004967:Estrogens; C485817:beta-tricalcium phosphate; C018392:tricalcium phosphate