Alternation of Nephron Morphology Associated with Sustained Delivery of Danazol Using Adult Male Rodents as a Model

Hormonal replacement therapy (HRT) has shown to be efficacious in treatment and preventing of heart disease, osteoporosis and reducing mortality in hypogonadal males. Several attempts to utilize the native testosterone and its analog such as danazol 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 danazol on the functional and structural capacity of the kidney using adult male rats as a model. A total of 24 adult male rats were subdivided into four equal groups. Groups I and II were castrated 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 danazol. Rats in group IV were unimplanted and untreated to be served as a control group. At the end of 90 days post treatment the animals were sacrificed by using overdose of isoflurane 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 danazol at a sustained level for 60 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 danazol compared to control, (iii) sustained delivery of danazol resulted in a maintenance of kidney weights compared to the control level, however, the lack of danazol treatment resulted in a remarkable regression in the kidney weights of castrated rats, (iv) histopathological evolutions of renal tubules revealed tubular epithelial damage in intact rats received danazol treatment compared to the control and other groups. In conclusion, this study suggests that exogenous danazol therapy could lead to profound tubular damage and consequently major renal insufficiency.