SOD2 mRNA as a potential biomarker for exercise: interventional and cross-sectional research in healthy subjects.

The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono-nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034).

Compromised glutathione synthesis results in high susceptibility to acetaminophen hepatotoxicity in acatalasemic mice.

Acatalasemia is caused by genetic defect in the catalase gene. Human achatalasemia patients are able to scavenge physiological hydrogen peroxide but are vulnerable to exogenous oxidative stress. In the present study, we used an acetaminophen-induced hepatotoxicity model in acatalasemic mice to explore this vulnerability. Interestingly, the acetaminophen-induced decrease in total glutathione levels was more prolonged in acatalasemic mice. While the subunits of glutamate-cysteine ligase, a glutathione synthase enzyme, were increased by acetaminophen in the liver of wild-type mice, their expression was lower and was further reduced by acetaminophen in acatalasemic mice. This feature was also observed in immortalized hepatocytes derived from the livers of these mice. However, when catalase was knocked down in HepG2 cells, a cultured human liver cell line, the expression of glutamate-cysteine ligase subunits was increased, suggesting that the low expression of glutamate-cysteine ligase subunits in acatalasemia may be due to other mechanism than catalase deficiency. Therefore, when other factors were investigated, it was found that transforming growth factor-ß1 was up-regulated by acetaminophen in the liver of acatalasemic mice, which may inhibit the expression of glutamate-cysteine ligase subunits. The results of this study suggest a new toxic mechanism of acetaminophen-induced liver injury in patients with acatalasemia.

Effects of administration of Bifidobacterium animalis subsp. lactis GCL2505 on defecation frequency and bifidobacterial microbiota composition in humans.

The aim of this study was to evaluate the changes in endogenous bifidobacteria and administered Bifidobacterium animalis subsp. lactis (B. lactis) GCL2505 (GCL2505) in the intestine after administration of GCL2505 by means of a randomized, placebo-controlled double-blind, cross-over study. An increase in the number of total bifidobacteria (the sum of B. bifidum, B. breve, B. longum subsp. longum, B. adolescentis, B. anglatum, B. catenulatum, B. pseudocatenulatum, B. dentium, B. longum subsp. infantis and B. lactis) in the feces were observed after administration of GCL2505 using species- and subspecies-specific real-time polymerase chain reaction analysis. However, the number of endogenous bifidobacteria species (excluding B. lactis) remained unchanged. B. lactis also became the predominant bifidobacterial species. Taking into account the number of GCL2505 administered, the findings further suggested that GCL2505 proliferated in the intestine. In addition, the defecation frequency increased during GCL2505 administration compared with the placebo. Moreover, a single administration study (n=17) clearly demonstrated that GCL2505 successfully reached the intestine before proliferating at least 10-fold. This is the first report to show an increase in intestinal bifidobacteria, with no changes to the endogenous species, and improvements in constipation following proliferation of administered bifidobacteria.