Effect of selenium-deficient diet on tubular epithelium in normal rats.

Selenium (Se) deficiency reduces glutathione peroxidase (GPx) activity, resulting in increased oxidative stress. We examined how Se deficiency induces renal injury via oxidative stress over time during the Se-deficient period. Seventy-two male Wistar rats were divided into two groups and fed either a control or Se-deficient diet. Rats were sacrificed on weeks 1, 2, 4, 6, 9, and 12. Blood and urine samples were collected, and the kidneys were removed. Urinalysis was performed, and creatinine clearance (Ccr) was calculated. Expressions of cellular GPx (cGPx) and phospholipid hydroperoxidase GPx (PHGPx) mRNA and GPx activity were measured. Histology was evaluated by light microscopy with immunohistochemistry for 4-hydroxy-2-nonenal (HNE) and vimentin. The Se-deficient diet caused significant decreases in GPx activity and cGPx mRNA expression but no change in PHGPx mRNA, together with significant proteinuria and glucosuria and slight decline in Ccr. The Se-deficient diet induced calcification in the kidney and increased the distribution of HNE and vimentin immunostaining in proximal tubuli, particularly around the outer medulla stripe. However, the histological damage did not progress after 6 weeks of deficiency. Se deficiency induces proteinuria and glucosuria with renal calcification, which may be primarily induced by injury of proximal tubuli via oxidative stress.

Characteristics of normal stromal components and their correlation with cancer occurrence in human prostate.

Prostate cancer is one of the most common age-related malignancies. The occurrence frequency of prostate cancer is very different according to prostate zones. The prostate stroma is an important element in growth and differentiation of the normal prostate and also has a close relationship to the occurrence of benign prostatic hypertrophy and cancer. We examined 14 cases of normal prostate tissues obtained at autopsy and 11 cases of prostate cancer tissues at radical prostatectomy specimens with cancers for clarifying the characteristics of stromal components in the normal prostate and the correlation between the stroma and the occurrence of prostate cancers. Stromal cells, such as smooth muscle cells, myofibroblasts and fibroblasts were identified by immunohistochemistry (IHC). Connective tissue fibers were detected by Elastica van Gieson and also IHC stain. Quantitative analysis of the smooth muscle tissue and connective tissue fibers were performed using a computer image analyzer system. In the normal prostate, stromal components varied in each zone. Every zone of the prostate contained smooth muscle cells, myofibroblasts, fibroblasts and collagen fibers. Elastic fibers were clearly visible in the transition zone. Smooth muscle cells were the main stromal component but less numerous in the frequent occurrence zone (peripheral zone) of prostate cancer (p<0.05). Myofibroblasts and fibroblasts were found either in normal or cancer tissues, although a few in number. The increase of collagen fibers accompanied decrease of smooth muscle cells as prostate cancer grade increased (p<0.05). The characteristics of stromal components and their amounts in the normal prostate appear to correlate with a distinct predilection for cancer occurrence in the peripheral zone and a weak stromal reaction in prostate cancers.