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Apocynin exerts cardioprotection in ischemia/reperfusion (I/R) by inhibiting superoxide release from NADPH oxidase
Author(s) -
Bartol Kyle D,
Habtamu Tsion,
Tolson Jasmine,
Koko Deima,
Diaz Brian,
Murphy Ryan,
Chen Qian,
Young Lindon
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1136.16
Subject(s) - apocynin , nadph oxidase , superoxide , cardioprotection , chemistry , reactive oxygen species , oxidase test , pharmacology , phorbol , superoxide dismutase , ischemia , medicine , endocrinology , protein kinase c , biochemistry , oxidative stress , signal transduction , enzyme
I/R results in a marked cardiac contractile dysfunction. Inhibiting superoxide (SO) release via NADPH oxidase may preserve cardiac contractile function following I/R. Apocynin (MW= 166) inhibits NADPH oxidase by blocking the translocation of p47 phox to the membrane. We studied isolated rat hearts following ischemia (30 min) and reperfusion (45 min). Control I/R hearts (n=5) recovered to 41 ± 8% and 30 ± 6% of baseline values for left ventricular developed pressure (LVDP) and the rate of LVDP (+dP/dt max ) respectively at the end of reperfusion. Apocynin (400μM, n=3) given at reperfusion significantly restored LVDP (p<0.05) and +dP/dt max (p<0.01) by 81 ± 5% and 80 ±3%, respectively, at 45 minutes post reperfusion compared to I/R hearts. Phorbol 12‐myristate 13‐acetate (PMA, 100nM, n=12) and N‐formyl‐L‐methionyl‐ L‐phenylalanine (fMLP, 1μM, n=27) stimulated neutrophil SO release was measured spectrophotometrically. Apocynin dose dependently attenuated fMLP and PMA stimulated neutrophil SO release by 63 ± 8% (400μM, n=11, p<0.01), 81 ± 9% (1mM, n=10, p<0.01), and 29 ± 5% (400μM, n=10, p<0.05), 47 ± 6% (1mM, n=10, p<0.01), respectively. These results suggest that apocynin attenuates post I/R cardiac contractile dysfunction by inhibiting the release of SO from NADPH oxidase in post reperfused tissues.