Dexamethasone treatment alters kinetics properties of liver mitochondrial F 0 .F 1 -ATPase and membrane lipid profiles in developing and adult rats

Abstract

Dexamethasone—a potent synthetic glucocorticoid—has multiple diagnostic and therapeutic applications in wide range of age groups. However, the side-effects of dexamethasone (Dex) treatment including those on development are becoming increasingly apparent. Since the developmental processes are energy-dependent, we examined the effects of chronic Dex treatment on kinetics properties of liver mitochondrial F0.F1-ATPase and mitochondrial membrane lipid profiles in rats belonging to different developmental age groups (2, 3, 4 and 5 weeks) and in adults (~8 weeks). The animals were treated with a subcutaneous dose of 2 mg of Dex/kg body weight (or saline as vehicle) for three alternative days (at around 7.00 A.M.) prior to the day of sacrifice. Dex treatment resulted in significant reduction in F0.F1-ATPase activity in developmental age groups and in adults as compared to their age-matched vehicle-treated control group. The substrate kinetics analysis of F0.F1-ATPase resolved Km and Vmax values in 3 components in all the control age groups; whereas Dex treatment significantly altered the Km and Vmax values or abolished the entire components in age-specific manner. Dex treatment significantly lowered the energy of activation and altered phase transition temperature (TtoC) in all the developmental age groups and in adults. Dex treatment significantly increased the contents of total phospholipid (TPL), individual phospholipids classes and cholesterol (CHL) in all the developmental age groups whereas opposite pattern was observed in adults. The mitochondrial membrane became more fluidized in the developing age groups (2, 4 and 5 weeks); whereas no change was observed in 3-week and adult groups following Dex treatment. In present study, our data demonstrate comprehensive deleterious effects of chronic Dex treatment on liver mitochondrial membrane structure and F0.F1-ATPase functional properties with respect to energy metabolism. At the same time, our data also warns against excessive repeated use of antenatal DEX in treatments in growing and adult human patients.