Protein Expression in the Gastrocnemius Muscle of a Rodent Shrapnel-Injury Model

With shrapnel injuries, the metal fragment is usually left in place to reduce the risk of morbidity extensive surgery might bring. This means the individual may retain those metals for the remainder of their life. Often the long-term health effects of the embedded metal are not known, especially with respect to protein damage and perturbations of muscle repair pathways. In this study, using homogenates of rat gastrocnemius muscle implanted with pellets of military-relevant metals, we investigated expression of iNOS and eNOS, enzymes involved in nitric oxide production, as well as MMP-2 and MMP-9, matrix metalloproteinases associated with muscle repair. In addition, hydroxynonenal-modified proteins were investigated to assess metal-induced oxidative damage and metal levels in the gastrocnemius determined. Metals were implanted for up to 12 months in order to determine the long-term effects on the expression of muscle-associated proteins. With the exception of iron and cobalt at 1-month post-implantation, there were no significant differences in metal levels in the gastrocnemius in any of the cohorts. Protein expression analysis showed significant decreases in iNOS and eNOS in the 6-month and 12-month lead and depleted uranium groups. Hydroxynonenal-modified proteins were also significantly increased in the iron, copper, lead, and depleted uranium groups. These results suggest that some embedded metals can induce long-term oxidative damage, as well as affect enzyme systems involved in signal transduction.