Effect of dexamethasone treatment on oxidative energy metabolism in rat liver mitochondria during postnatal developmental periods.
Dexamethasone--a potent synthetic glucocorticoid--has multiple therapeutic applications and is 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 and the adult groups. Oxidation of succinate was severely impaired in all the age groups. 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.
Pandya
Jignesh D
JD
Department of Biochemistry, Faculty of Science, M.S. University of Baroda, Vadodara, Gujarat, India. jdpandya@buffalo.edu
Agarwal
Neeraj A
NA
Katyare
Surendra S
SS
D000367:Age Factors; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats
D008293:Malates; D018698:Glutamic Acid; D003907:Dexamethasone; C030298:malic acid; D019289:Pyruvic Acid