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Dexamethasone reduces the antinociceptive effects of centrally administered selective opioid agonist
94
Pharmacological
Research, VU. 26, Supplement I, 1992
DEXAMETHASONE REDUCES THE ANTINOCICEPTIVE EFFECTS OF CENTRALLY ADMINISTERED SELECTIVE OPIOID AGONIST S. Pieretti, A. Di Giammario, A. Loizzo, A. Capasso*and L. Sorrentino* Dept. of Pharmacology, Istituto Superioredi Sanita’,Rome; * Dept. of Exp. Pharmacology, University of Naples Federico II. We have previously demonstratedthat antinociception induced by morphine was reducedby dexamethasone(DEX) pretreatmentand potentiatedby pretreatmentwith the glucocorticoid receptor antagonist RU 38486 (l-2). Since the anthtociceptiveeffects produced by central administration of opioid agonist appearto be mediated by the stimulation of different opioid receptors(3) we decided to study the effects of DEX on the antinociception induced in mice by centrally administered morphine (2 mnol/mouse),~endorphin (0.6 mnol/mouse),DAGO (0.1 mnol/mouse), DPDPE (1 nmohmouse) and U 50488 (50 nmol/mouse).The results obtained in our experimentsindicate that DEX administered at the dosesof 0.1 and 1 mg/lcg 2 hr before opiate agonist is able to interfere with antinociceptive effects induced by morphine+endorphin and DAGO while is not able to change antinociception induced by DPDPE and U 50488. These results may indicate the possibility that DEX interference on opioid system may be due to interaction at least with “mu” opioid receptor sites. References 1) Calignano A., Persico P., Sorrentino L. Pharmac.Res. Comm. 20,225-226 (1988) 2) Pieretti S., CapassoA., Di Giammario A., Loizzo A, Sorrentino L. Gen. Pharmacol. 22,929-933 (1990) 3) Suh H.H. and Tseng L.F. Pharmacol.Biochem. Behav. 35,807-813 (1990)
ROLE OF “OXIDATIVE
STRESS ” IN ACUTE ADRIAMYCIN
TOXICITY
Pietro Paolo Elia, Giuseppe Ambrosia, Pliio Cirillo, Annalisa Scognamiglio, IsabellaTritto, *Antonio Basso, *Walter Polverino, Massimo Chiariello. Divisions of Cardiology, 2nd School of Medicine, University of Naples, and *Istituto dei Tmnorl Pascale, Naples, Italy. Oxygen radical formation has been implicated in the patiogenesis of cardiac toxicity by adriamicin (ADR). However, the mechanisms of ADR toxicity are poorly characterized. “Oxidative stress” is one im ortant effect of oxygen radical attack. To investigate whether acute ADR toxici is associated WI4 occurrence of oxidative stress, isolated rabbit hearts were per-!&cd with ADR (33 received ADR plus the
ADR ADR+MPG
DP base 104s 98i5
DP W-O 54&l 1 83k7*
EDP base 8*1 llfl
EDP W-O 395~12 14&2*
PP base lPl?E-0 77s 90&7* 77k2
Cumulative release of GSSG was 202534 nMoles/gr in ADR group, while in ADR+MPG hearts was 236*41 nMoles/gr @=NS). Thus, OUTdata indicate that aclriamicin can exert acute cardiac toxicity, via a mechanism not involving oxidative stress. This acute toxicity of ADR can be prevented by the oxygen radical scavenger mercapto-propionylglycine.
Pharmacological
Research, VU. 26, Supplement I, 1992
DEXAMETHASONE REDUCES THE ANTINOCICEPTIVE EFFECTS OF CENTRALLY ADMINISTERED SELECTIVE OPIOID AGONIST S. Pieretti, A. Di Giammario, A. Loizzo, A. Capasso*and L. Sorrentino* Dept. of Pharmacology, Istituto Superioredi Sanita’,Rome; * Dept. of Exp. Pharmacology, University of Naples Federico II. We have previously demonstratedthat antinociception induced by morphine was reducedby dexamethasone(DEX) pretreatmentand potentiatedby pretreatmentwith the glucocorticoid receptor antagonist RU 38486 (l-2). Since the anthtociceptiveeffects produced by central administration of opioid agonist appearto be mediated by the stimulation of different opioid receptors(3) we decided to study the effects of DEX on the antinociception induced in mice by centrally administered morphine (2 mnol/mouse),~endorphin (0.6 mnol/mouse),DAGO (0.1 mnol/mouse), DPDPE (1 nmohmouse) and U 50488 (50 nmol/mouse).The results obtained in our experimentsindicate that DEX administered at the dosesof 0.1 and 1 mg/lcg 2 hr before opiate agonist is able to interfere with antinociceptive effects induced by morphine+endorphin and DAGO while is not able to change antinociception induced by DPDPE and U 50488. These results may indicate the possibility that DEX interference on opioid system may be due to interaction at least with “mu” opioid receptor sites. References 1) Calignano A., Persico P., Sorrentino L. Pharmac.Res. Comm. 20,225-226 (1988) 2) Pieretti S., CapassoA., Di Giammario A., Loizzo A, Sorrentino L. Gen. Pharmacol. 22,929-933 (1990) 3) Suh H.H. and Tseng L.F. Pharmacol.Biochem. Behav. 35,807-813 (1990)
ROLE OF “OXIDATIVE
STRESS ” IN ACUTE ADRIAMYCIN
TOXICITY
Pietro Paolo Elia, Giuseppe Ambrosia, Pliio Cirillo, Annalisa Scognamiglio, IsabellaTritto, *Antonio Basso, *Walter Polverino, Massimo Chiariello. Divisions of Cardiology, 2nd School of Medicine, University of Naples, and *Istituto dei Tmnorl Pascale, Naples, Italy. Oxygen radical formation has been implicated in the patiogenesis of cardiac toxicity by adriamicin (ADR). However, the mechanisms of ADR toxicity are poorly characterized. “Oxidative stress” is one im ortant effect of oxygen radical attack. To investigate whether acute ADR toxici is associated WI4 occurrence of oxidative stress, isolated rabbit hearts were per-!&cd with ADR (33 received ADR plus the
ADR ADR+MPG
DP base 104s 98i5
DP W-O 54&l 1 83k7*
EDP base 8*1 llfl
EDP W-O 395~12 14&2*
PP base lPl?E-0 77s 90&7* 77k2
Cumulative release of GSSG was 202534 nMoles/gr in ADR group, while in ADR+MPG hearts was 236*41 nMoles/gr @=NS). Thus, OUTdata indicate that aclriamicin can exert acute cardiac toxicity, via a mechanism not involving oxidative stress. This acute toxicity of ADR can be prevented by the oxygen radical scavenger mercapto-propionylglycine.