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J Neurosurg Anesthesiol · Oct 2015
Changes in Energy Levels by Dexamethasone in Ischemic Hearts and Brains in Male Mice.
- Toshihiro Yorozuya, Chikara Namba, Naoto Adachi, Kazuo Nakanishi, Kentaro Dote, and Takumi Nagaro.
- Department of Anesthesia and Perioperative Medicine, Ehime University Graduate School of Medicine, Ehime, Japan.
- J Neurosurg Anesthesiol. 2015 Oct 1; 27 (4): 295-303.
BackgroundGlucocorticoids have been shown to alleviate ischemia-induced myocardial injury, while aggravating neuronal damage caused by ischemia. As energy failure is a predominant factor in cellular viability, we examined the effects of glucocorticoids on energy utilization in the mouse heart and brain.MethodsSeventy-two male ddY mice were assigned to 1 of 3 groups: saline (S), dexamethasone (a glucocorticoid without mineralocorticoid activity, 5 mg/kg) (D), and metyrapone (a potent inhibitor of the synthesis of glucocorticoids, 100 mg/kg) (M) groups (n=24 in each). Three hours after intraperitoneal administration, all animals were decapitated, and the heads were frozen in liquid nitrogen after 0, 0.5, 1, or 2 minutes (n=6 in each). The hearts were immediately removed and frozen in liquid nitrogen after 0, 5, 10, or 20 minutes of incubation at 37°C (n=6 in each). The concentrations of adenylates and monoamines were determined by high-performance liquid chromatography.ResultsIn the heart, the adenosine 5'-triphosphate (ATP) concentration did not differ among the 3 groups at 0 minute of ischemia (3 h of S, D, or M treatment). Ischemia for 5 minutes decreased the ATP content to 21% of the basal level in the S group. The ATP decrease was suppressed by either the D or M treatment, such that after 5 minutes ATP levels were 63% and 64% of each basal level, respectively. In the brain, the ATP level in the M group was 62% of that in the S group at 0 minute of ischemia, and the 5'-monophosphate (AMP) level was 276% of that in the S group. Brain dopamine metabolism was facilitated by dexamethasone, and suppressed by metyrapone.ConclusionsThe relationship between effects of glucocorticoids on ischemia-induced changes in energy levels and cellular viability was not clearly elucidated.
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