Effect of Dexamethasone Treatment on Oxidative Energy Metabolism in Rat Liver Mitochondria During Postnatal Developmental Periods

Abstract

Dexamethasone — a potent synthetic glucocorticoid — has multiple therapeutic applications and, used in all age groups, as well as for antenatal and perinatal treatments. However, side‐effects of dexamethasone treatment, including those on development, are becoming increasingly apparent. Since developmental processes are energy‐dependent, we examined the effects of chronic dexamethasone treatment on oxidative energy metabolism in liver mitochondria from rats belonging to different developmental age groups. Dexamethasone treatment adversely affected the state 3 respiration rates in 2‐ and 3‐week groups and in the adults with glutamate as the substrates, whereas for pyruvate + malate, the adverse effects were seen for the 3 week rats and the adult groups. Oxidation of succinate was severely impaired in all the age groups rats. For ascorbate + TMPD as the substrate, elevated respiration was noted for the 5‐week group and the impaired oxidation was observed in adults. Dexamethasone treatment also resulted in site‐specific uncoupling with the effect being seen predominantly in the 3‐ and 5‐week and adult animals. The activity of dehydrogenases decreased in a manner comparable to the respiration rates. The mitochondrial cytochromes decreased in an age‐dependent manner. The ATPase activity also decreased significantly. The results thus emphasize the adverse effects of dexamethasone treatment on mitochondrial energy metabolism especially in critical age groups.