Journal: Translational Research
Article Title: The role of acid-base imbalance in statin-induced myotoxicity
doi: 10.1016/j.trsl.2016.03.015
Figure Lengend Snippet: Time course interconversion of simvastatin lactone (SVL) and pravastatin lactone (PVL) in phosphate buffer saline at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with phosphate buffer saline of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 48 hours at 37°C. The percentages of lactone and hydroxy acid form recovered at different time points are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. Time course interconversion of SVL shows disappearance of SVL ( A ) and formation of simvastatin hydroxy acid form ( B ). a = pH 7.8 vs pH 6.8, 7.0 ( P < 0.001); pH 7.8 vs pH 7.2 ( P < 0.05). b = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001); pH 7.2 vs pH 7.4 ( P < 0.05). c = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 7.6 ( P < 0.01); pH 7.6 vs pH 7.8 ( P < 0.05). e = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05). f = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001). g = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 7.4, 7.6, 7.8 ( P < 0.001). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 6.8 vs pH 7.6, 7.8; pH 7.0 vs pH 7.6, 7.8; pH 7.2 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 6.8, 7.8; pH 7.2 vs pH 7.6 ( P < 0.01); pH 7.0 vs pH 7.4 ( P < 0.05). b = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8 ( P < 0.001); pH 7.0 vs pH 7.2 ( P < 0.01). c = pH 6.8 vs pH 7.2, 7.4, 7.6, 7.8; pH 7.0 vs 7.2, 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 6.8 vs pH 7.0 ( P < 0.01); pH 7.4 vs pH 7.6 ( P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.4, 7.6, 7.8 ( P < 0.001). e = 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8; pH 7.2 vs pH 7.6, 7.8, ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); pH 7.2 vs pH 7.4 ( P < 0.05). f = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 ( P < 0.001). g = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8 ( P < 0.001).
Article Snippet: Simvastatin lactone (SVL, 99.3%) and pravastatin hydroxy acid sodium (PVA, 99.4%) were purchased from Kemprotec Ltd (Lancashire, UK), simvastatin hydroxy acid ammonium salt (SVA, 98.0%) and pravastatin lactone (PVL, 98%) from Toronto Research Chemicals Inc (Toronto, Canada), lovastatin hydroxy acid sodium (LOV-A, 98.0%) and griseofulvin (97.0%) from Alfa-Aesar (Lancashire, UK), lovastatin lactone (LOV-L, 97.0%) from Cayman (Leicestershire, UK), and 4,4-dichlorodiphenyltrichloroethane (98.0%) from Sigma–Aldrich (Dorset, UK).
Techniques: Saline, Incubation, Modification, Concentration Assay, Standard Deviation