Ornithine Phenylacetate

Osteoporosis is the most common bone disease, characterized by decreased bone mineral density (BMD) and often associated to decreased muscle mass and function. Metal exposure plays a role in the pathophysiology of osteoporosis and affects also muscle quality. The aim of this study was to assess the association between metal levels in bone and muscle samples and the degeneration of these tissues. A total of 58 subjects (30 male and 28 female) was enrolled and classified in osteoporotic (OP, n = 8), osteopenic (Ope, n = 30) and healthy (CTR, n = 20) subjects, according to BMD measures. Femoral head bone samples and vastus lateralis muscle samples were collected during hip arthroplasty surgeries. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed increased levels of Al, Cd and Pb in OP and Ope bone tissue compared to CTR subjects (p = 0.04, p = 0.005 and p = 0.01, respectively). Whereas, increased levels of Co, Cd and Pb were measured in OP and Ope muscle tissues, compared to CTRs (p < 0.001, p = 0.02 and p = 0.01, respectively). In addition, Al, Cd and Pb levels in bone and Cd and Co levels in muscle were negatively correlated with BMD. A negative association among Co, Cd, Cr and Hg levels and muscle fibers diameter was also observed in muscle tissues. This study assessed that metal exposure can affects bone and muscle tissue quality and may contribute to the onset and progression of musculoskeletal diseases such as osteoporosis. Therefore, it is important to implement metal exposure assessment and their impact on disease development, in order to manage and prevent metal accumulation effects on bone and muscle quality.

In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field.

We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2′deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times.

The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day.

Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.