Expression of extracellular glutathione peroxidase in human and mouse gastrointestinal tract.

Extracellular glutathione peroxidase (EGPx) is a glycosylated selenoprotein capable of reducing hydrogen peroxide, organic hydroperoxides, free fatty acid hydroperoxides, and phosphatidylcholine hydroperoxides. We found that human large intestinal explant cultures synthesize EGPx and cellular glutathione peroxidase (CGPx) and secrete EGPx. The level of EGPx mRNA expression relative to alpha-tubulin was similar throughout the mouse gastrointestinal tract. EGPx mRNA transcripts have been localized to mature absorptive epithelial cells in human and mouse large intestine. Western blot analysis of mouse intestinal protein has demonstrated the presence of EGPx protein in the small intestine, cecum, and large intestine, with the highest protein levels found in the cecum. Immunohistochemistry studies of human large intestine and mouse small and large intestine sections demonstrated the presence of EGPx protein within mature absorptive epithelial cells. In human large intestine and mouse small intestine, EGPx protein is also present in the extracellular milieu. These results suggest a role for EGPx in protection of the intestinal tract from peroxidative damage and/or in intercellular metabolism of peroxides.

Plasma glutathione peroxidase and its relationship to renal proximal tubule function.

Selenium-dependent extracellular glutathione peroxidase (E-GPx) is found in plasma and other extracellular fluids. Previous studies have indicated that patients with chronic renal failure on dialysis have low plasma GPx activity. In this study, dialysis patients had approximately 40% of control plasma GPx activity, while anephric individuals had lowest plasma GPx activities ranging from 2 to 22% of control. The residual plasma GPx activity in anephric individuals could be completely precipitated by anti-E-GPx antibodies, indicating that all plasma GPx activity can be attributed to E-GPx in both normal and anephric individuals. Plasma GPx activity rises rapidly following kidney transplantation, often reaching normal values within 10 days. The plasma GPx activity in some transplanted patients rises to levels higher than the normal range, followed by a return to the normal range. Since E-GPx in the kidney is primarily synthesized in the proximal tubules, we investigated whether nephrotoxic agents known to disrupt proximal tubule function also affected plasma GPx activity. The beta-lactam antibiotic cephaloglycin rapidly caused a decrease in plasma GPx activity in rabbits. In addition, the chemotherapeutic agent ifosfamide caused a decrease in plasma GPx activity in pediatric osteosarcoma patients. Fanconi syndrome associated with either ifosfamide therapy or valproic acid therapy also caused a decrease in plasma GPx activity. Thus plasma GPx activity is related to kidney function and is decreased in certain situations where nephrotoxic drugs are administered. Monitoring plasma GPx activity may have predictive value in evaluating the function of transplanted kidneys or in predicting those patients particularly at risk of nephrotoxic injury associated with certain medications.

Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence.

Phytoestrogens represent a family of plant compounds that have been shown to have both estrogenic and antiestrogenic properties. A variety of these plant compounds and their mammalian metabolic products have been identified in various human body fluids and fall under two main categories: isoflavones and lignans. A wide range of commonly consumed foods contain appreciable amounts of these different phytoestrogens. For example, soy and flax products are particularly good sources of isoflavones and lignans, respectively. Accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials suggests that phytoestrogens may potentially confer health benefits related to cardiovascular diseases, cancer, osteoporosis, and menopausal symptoms. These potential health benefits are consistent with the epidemiological evidence that rates of heart disease, various cancers, osteoporotic fractures, and menopausal symptoms are more favorable among populations that consume plant-based diets, particularly among cultures with diets that are traditionally high in soy products. The evidence reviewed here will facilitate the identification of what is known in this area, the gaps that exist, and the future research that holds the most potential and promise.