The use of androgen loaded tcpl delivery devices to assess the proinflammatory cytokines profiles
Benghuzzi, H.; Tucci, M.
Biomedical Sciences Instrumentation 44: 94-99
2008
ISSN/ISBN: 0067-8856 PMID: 19141899 Document Number: 618056
The goal of this study is to investigate the pathophysiological changes, of both local and systemic control factors (cytokines and structural alterations), associated with continuous and sustained delivery of T and DHT using tricalcium-phosphate-lysine (TCPL) delivery devices. A total of 32 adult male Sprague Dawley rats were equally divided into four equal groups. Animals in group 1 were left untreated and served as intact control. Animals in group 2 were implanted with an empty ("sham") drug delivery device, and animals in groups 3 and 4 were implanted with a drug delivery carrier containing either DHT or T, respectively. Animal weights were recorded weekly and blood was collected bi-weekly over a six week period. At the end of 21 days, the animals were euthanized and blood and organs were collected, analyzed, and statistically evaluated. Data obtained from this study demonstrated that supraphysiological levels of androgens given in a sustained manner for long duration to adult male rats resulted in an increased level of IL-6, as well as, major alterations in lipoprotein profiles (total cholesterol, VLDL/LDL, and HDL). Histopathological evaluations of vital (heart, kidney and adrenal tissues) and major reproductive organs revealed structural damage. Histological evaluation of myocardial (ventricle and apex) tissues suggests evidence of hypertrophy and early inflammatory infiltrate. As androgens are considered for potential treatments of pathophysiological disorders, more research is needed to determine if the changes which occur as a result of sustained release of high levels of androgens can be reversed upon removal of the drug.