The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.

Many key metabolic and physiologic functions involve arginine and arginine-derived metabolites. Requirements for arginine, a “conditionally essential” amino acid for most mammalian species, are met in variable proportions by dietary intake and endogenous synthesis, the latter being sufficient to fulfill arginine needs in adult humans and mice under nonpathologic conditions. However, dietary arginine restriction causes orotic aciduria and abnormal function of the urea cycle. Furthermore, the importance of dietary arginine in the maintenance of homeostasis of arginine-derived metabolites in the body has not yet been analyzed in detail. We therefore examined whether the deprivation or supplementation of dietary arginine affects tissue and circulating levels of arginine-derived polyamines. We pair-fed male Swiss albino mice (30 g) for 15 or 30 d synthetic diets containing 0, 1.12 or 2.24 g/100 g L-arginine. Tissue and blood levels of the main free polyamines, putrescine, spermidine and spermine, were measured by HPLC. In general, neither the deprivation nor the supplementation of arginine dramatically affected the levels of any of the polyamines analyzed. Variations were organ, time and polyamine specific, and most differences were in the levels of putrescine at 15 d and of spermidine at 30 d. Thus, in contrast to effects on urea cycle function, dietary arginine does not appear to be essential for the maintenance of the homeostasis of free polyamine levels in adult mice, emphasizing the importance of endogenous arginine synthesis in preserving the polyamine body pool.

Despite the rising incidence of osteoporosis (the most common bone disorder) as life expectancy increases worldwide, the genetic and metabolic factors contributing to this multifactorial disease are still poorly understood. This study investigated the role of arginine metabolism in bone formation and its potential for preventing bone loss in postmenopausal osteoporosis. The osteogenic effects of arginine were evaluated in vitro by determining calcium mineral deposition and the expression of marker genes in the human osteoblastic cell line Saos-2. In vivo analyses were conducted in ovariectomized mice treated with arginine, focusing on femoral bone microarchitecture, marker gene expression and serum metabolite profiles. Arginine treatment enhanced calcium deposition and osteoblastic differentiation in vitro. In contrast, however, this treatment had a deleterious effect in vivo, exacerbating trabecular bone loss. These results are particularly relevant given the wide availability of arginine as a dietary supplement, and our findings underscore the necessity of verifying the safety of nutritional supplements in different populations and in the presence of disease.