Gestational hypermethioninaemia alters oxidative/nitrative status in skeletal muscle and biomarkers of muscular injury and inflammation in serum of rat offspring.

Abstract

In this study we evaluated oxidative/nitrative stress parameters (reactive oxygen species production, lipid peroxidation, sulfhydryl content, superoxide dismutase, catalase and nitrite levels), as well as total protein content in the gastrocnemius skeletal muscle of the offspring of rats that had been subjected to gestational hypermethioninaemia. The occurrence of muscular injury and inflammation was also measured by creatine kinase activity, levels of creatinine, urea and C-reactive protein and the presence of cardiac troponin I in serum. Wistar female rats (70-90days of age) received methionine (2.68μmol/g body weight) or saline (control) twice a day by subcutaneous injections during the gestational period (21days). After the rats gave birth, pups were killed at the twenty-first day of life for removal of muscle and serum. Methionine treatment increased reactive oxygen species production and lipid peroxidation and decreased sulfhydryl content, antioxidant enzymes activities and nitrite levels, as well as total protein content in skeletal muscle of the offspring. Creatine kinase activity was reduced and urea and C-reactive protein levels were increased in serum of pups. These results were accompanied by reduced muscle mass. Our findings showed that maternal gestational hypermethioninaemia induced changes in oxidative/nitrative status in gastrocnemius skeletal muscle of the offspring. This may represent a mechanism which can contribute to the myopathies and loss of muscular mass that is found in some hypermethioninaemic patients. In addition, we believe that these results may be relevant as gestational hypermethioninaemia could cause damage to the skeletal muscle during intrauterine life.