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Luteolinidin, a naturally occurring flavonoid, decreases ischemia/reperfusion injury through inhibition of CD38 and preservation of NADPH and BH 4 (547.14)
Author(s) -
Boslett James,
De Pascali Francesco,
Hemann Craig,
Zweier Jay
Publication year - 2014
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.28.1_supplement.547.14
Subject(s) - ischemia , chemistry , reperfusion injury , medicine , enos , cardiology , pharmacology , endocrinology , nitric oxide , nitric oxide synthase
CD38, a consumer of NAD+ and NADP+, is activated in I/R, leading to depletion of myocardial NADP(H) and consequently, lower eNOS function due to low levels of cofactor NADPH. Isolated hearts were subjected to two treatments: pre‐ischemic luteolinidin (25μM) infusion or vehicle control infusion (empty liposomes). In vehicle‐treated hearts at 30’ ischemia and 30’ reperfusion, NADPH and BH 4 were depleted by 67% and 64% respectively. With 3’ of luteolinidin infusion (25μM), these numbers changed to 23% and 32% for NADPH and BH 4 , respectively, representing an impressive 44% salvage of NADPH, and a 32% salvage of BH 4 compared to vehicle‐treated hearts. This NADPH and BH 4 salvage was manifested physiologically as an increased loss of coronary flow (CF) in response to eNOS inhibitor L‐NAME (1mM) at 30’ reperfusion. Moreover, we found in luteolinidin‐treated hearts more post‐ischemic recovery of rate pressure product, left ventricular developed pressure and CF, and, a less elevated end diastolic pressure. This work suggests that inhibition of CD38 with luteolinidin is beneficial in I/R as measured by parameters of post‐ischemic endothelial and contractile function. The work also suggests that that post‐ischemic NADPH and BH 4 levels are related, possibly through modulation of dihydrofolate reductase activity by NADPH levels. Grant Funding Source : Supported by 784