Increased levels of
glucocorticoids (GC) can result in major complications such
hypertension and
vascular injury. Chronically, this condition may lead to impairment of renal function.
Glucocorticoid excess was considered the etiologic agent that triggers over production of
reactive oxygen species (ROS). The mode of action of ROS was implicated to disrupt
nitric oxide availability in the vascular endothelium, leading to vascular complications. To circumvent this damage attempts were made to use
antioxidants in order to counter-balance the oxidative process. The objectives of this study were: (1) to establish an animal model of increased
glucocorticoid levels by sustained delivery and (2) to determine if sustained delivery of
selenomethionine in combination with
glucocorticoids could protect kidney tubular structures using adult rats. Sixteen female rats were divided into four equal groups (control and 3 experimental groups implanted with
tricalcium phosphate lysine drug delivery systems (TCPL) charged with either 50mg
selenomethionine (Se), 50 mg
corticosterone (C), or 50 mg of both C and Se). At the end of 24 days, the rats were sacrificed and both kidneys were removed for histopathological analysis. Quantitative analysis was performed on serum
calcium levels,
body weights and kidney weights in animals from all groups. Kidney slides were screened for possible structural damage. Sustained release of Se and Se+C resulted in a significant reduction of glomerular area (p < 0.05). Data obtained indicated that C, Se and Se+C administration caused a reduction in serum
calcium levels compared to control animals. The reduction may be in part to changes in
calcium-filtered load, changes in glomerular filtration rates or interference of
calcium absorption from the gut. In conclusion, data obtained from this investigation provided the literature with significant information regarding the role of sustained delivery of supraphysiological levels of
corticosterone in modifying kidney structure and function (possibly alter blood pressure).