1.4-Hydroxy-2-nonenal induces calcium overload via the generation of reactive oxygen species in isolated rat cardiac myocytes.
Nakamura K1, Miura D, Kusano KF, Fujimoto Y, Sumita-Yoshikawa W, Fuke S, Nishii N, Nagase S, Hata Y, Morita H, Matsubara H, Ohe T, Ito H. J Card Fail. 2009 Oct;15(8):709-16. doi: 10.1016/j.cardfail.2009.04.008. Epub 2009 Jun 18.
BACKGROUND: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca(2+) overload.
2.Simultaneous determination of propranolol and 4-hydroxy propranolol in human plasma by solid phase extraction and liquid chromatography/electrospray tandem mass spectrometry.
Partani P1, Modhave Y, Gurule S, Khuroo A, Monif T. J Pharm Biomed Anal. 2009 Dec 5;50(5):966-76. doi: 10.1016/j.jpba.2009.06.050. Epub 2009 Jul 7.
A very sensitive, reliable, reproducible and highly selective assay for the simultaneous determination of free and total (conjugated and unconjugated) propranolol and its equipotent hydroxyl metabolite, 4-hydroxy propranolol, in human plasma was developed and validated. The analytes were simultaneously extracted from 0.300 mL of human plasma using solid phase extraction and detected in positive ion mode by tandem mass spectrometry with a turbo ionspray interface. Deuterium-labeled propranolol and 4-hydroxy propranolol, propranolol-d7 and 4-hydroxy propranolol-d7, were used as internal standards. The method has a lower limit of quantitation (LOQ) of 0.20 ng/mL for both analytes with the limits of detection (LOD) 50 and 100 pg/mL for propranolol and 4-hydroxy propranolol, respectively, based on a signal-to-noise ratio of 5. The assay was linear over a range 0.20-135.00 ng/mL for free propranolol and 0.20-25.00 ng/mL for free 4-hydroxy propranolol and linear over range 1.
3.Microbial production of phase I and phase II metabolites of propranolol.
Marvalin C1, Azerad R. Xenobiotica. 2011 Mar;41(3):175-86. doi: 10.3109/00498254.2010.535219. Epub 2010 Nov 26.
1. The production in multimilligram amounts of 4- and 5-hydroxylated metabolites of (R)- or (S)-propranolol by biotransformation with two fungal strains, an Absidia sp. M50002 and a Cunninghamella sp. M50036, was carried out, starting from either the racemic drug or pure enantiomers. 2. While both enantiomers of propranolol were hydroxylated in the 5-position by incubation with strain M50002, the strain M50036 operated a chiral discrimination, resulting in the exclusive formation of the 4-hydroxy-(R)-enantiomer. 3. In addition, a Streptomyces sp. strain M52104, isolated from a soil sample, was selected for the high-yield regioselective β-glucuronidation of propranolol and its 4- and 5-hydroxylated derivatives. 4. NMR and mass spectroscopic data have been extensively used for the unambiguous characterization of 4- and 5-hydroxylated and glucuronidated derivatives, all of them corresponding to the major animal and human metabolites of propranolol, a typical substrate of CYP2D6.