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.
Highlights
Dexamethasone (Dex) is considered as a drug of choice for diagnosis and treatment of a wide range of pathological conditions in all the age groups in humans [1,2]
Results of our earlier studies indicated that the substrate oxidation rates and the ATP synthesizing ability of the isolated liver mitochondria were compromised in an age specific manner in the Dex-treated animals [19]
The adult group showed significant decrease in F0.F1-ATPase activity (21% decrease) following Dex treatment when measured at 37 ̊C; whereas no change in activity was observed at 25 ̊C
Summary
The use of Dex as potent glucocorticoids as well as an anti-inflammatory agent is recommended by American National Institutes of Health [2]. When it is used in pharmacological doses, adverse side-effects are seen in as high as 50% of the cases [12]. Our laboratory has demonstrated earlier that repeated exposure of Dex alters oxidative energy metabolism of mitochondria isolated from liver [19]. As it is well recognized the developmental processes are energy-dependent and the mitochondria play major role in ATP synthesis [20]. It is suggested that the results of our present study may provide possible explanation for energy functions/dysfunctions involved du- ring developmental period and in adult life following chronic exposure to Dex
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
