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: Interconversion of simvastatin and pravastatin between lactone and hydroxy acid forms in human plasma of different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with human plasma of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test (*** P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

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: Clinical Proteomics, Incubation, Modification, Concentration Assay, Standard Deviation

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: Interconversion of statins between lactone and hydroxy acid forms in phosphate buffer saline at different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with PBS of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of the lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test ( ∗∗∗ P < 0.001; ** P < 0.01). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

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

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: Interconversion of statins between lactone and hydroxy acid forms in Dulbecco's modified eagle medium culture medium at different pH levels. Simvastatin lactone ( A ), simvastatin hydroxy acid ( B ), pravastatin lactone ( C ), and pravastatin hydroxy acid ( D ) were incubated with Dulbecco's modified eagle medium culture medium of modified pH (6.8–7.8) at a concentration of 50 μmol/L for 24 hours at 37°C. The percentages of the lactone and hydroxy acid form recovered after 24 hours are expressed as mean ± standard deviation, (n = 6). Differences between samples of different pH were analyzed by one-way analysis of variance followed by Tukey's post hoc test ( ∗∗∗ P < 0.001). SVL, simvastatin lactone; SVA, simvastatin hydroxy acid; PVL, pravastatin lactone; PVA, pravastatin hydroxy acid.

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: Modification, Incubation, Concentration Assay, Standard Deviation

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 human plasma at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with human plasma 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 7.0 vs pH 7.6 ( P < 0.05); pH 7.4 vs pH 6.8, 7.8 ( P < 0.01); pH 6.8 vs pH 7.6, 7.8; pH 7.8 vs pH 7.0, 7.2 ( P < 0.001). b = 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). 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 ( P < 0.001); pH 7.6 vs pH 7.8 ( P < 0.05). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.2, 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 7.6 ( 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 7.6, 7.8 ( P < 0.001); pH 7.4 vs pH 7.2, 7.8 ( P < 0.05). Time course interconversion of PVL shows disappearance of PVL ( C ) and formation of pravastatin hydroxy acid form ( D ). a = pH 7.6 vs pH 6.8, 7.4 ( P < 0.01); pH 7.8 vs pH 6.8, 7.0, 7.2, 7.4; pH 7.2 vs pH 7.6 ( P < 0.001). 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 7.4, 7.6, 7.8; pH 7.4 vs pH 7.6, 7.8; pH 7.6 vs pH 7.8 ( P < 0.001). 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 ( P < 0.001). d = pH 6.8 vs pH 7.0, 7.2, 7.4, 7.6, 7.8; pH 7.0 vs pH 7.4, 7.6, 7.8 ( P < 0.001); pH 7.0 vs pH 7.2 ( P < 0.01).

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: Clinical Proteomics, Incubation, Modification, Concentration Assay, Standard Deviation

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

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 Dulbecco's modified eagle medium culture medium at different pH levels. The lactone forms of simvastatin and pravastatin were incubated with Dulbecco's modified eagle mediumculture medium 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, 7.2 ( P < 0.01). b = pH 6.8 vs pH 7.2 ( P < 0.05); pH 6.8 vs pH 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). c = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8; pH 7.4 vs 7.8 ( P < 0.001). d = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs 7.8 ( P < 0.01). e = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs pH 7.4, 7.8 ( P < 0.001). f = pH 6.8 vs pH 7.2, 7.4, 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 7.8 ( P < 0.01); pH 7.2 vs pH 7.8 ( P < 0.05). b = pH 6.8 vs pH 7.2, 7.4, 7.8; pH 7.8 vs pH 7.2, 7.4 ( P < 0.001). c = 6.8 vs pH 7.2, 7.4, 7.8; pH 7.2 vs 7.8 ( P < 0.001); pH 7.2 vs pH 7.4 ( P < 0.05). d = pH 6.8 vs pH 7.2, 7.4, 7.8 ( P < 0.001). e = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 6.8 vs pH 7.2 ( P < 0.05).

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: Modification, Incubation, Concentration Assay, Standard Deviation

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: The pH dependence of the hydrolysis of the lactone form of statins

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: Clinical Proteomics

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: Effect of pravastatin lactone (PVL) and pravastatin hydroxy acid (PVA) on the viability of undifferentiated and differentiated C2C12. Cells were cultured at a density of 4,000 cells/well and allowed to attach for 24 hours or to differentiate for 4 days, then exposed to increasing concentrations of PVL or PVA under acidic, neutral, and alkaline medium pH for 72 hours. Results are presented as mean ± standard deviation of 3 experiments, 8 replicates per experiment. Data were analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) Effects of PVL on cell viability of undifferentiated C2C12 myoblasts. a = pH 6.8 vs pH 7.8 ( P < 0.001); b = pH 6.8 vs pH 7.4 ( P < 0.05); pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8, pH 7.4 vs pH 7.8 ( P < 0.001). ( B ) Effects of PVL on cell viability of differentiated C2C12 myocytes. a = pH 7.4 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.8 ( P < 0.01); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001), pH 7.4 vs pH 7.8 ( P < 0.01); e = pH 6.8 vs pH 7.4, 7.8, pH 7.4 vs pH 7.8 ( P < 0.001). ( C ) Effect of PVA on cell viability of undifferentiated C2C12 myoblasts. a = pH 6.8 vs pH 7.8 ( P < 0.01); b = pH 6.8 vs pH 7.8 ( P < 0.001). ( D ) Effect of PVA on cell viability of differentiated C2C12 myocytes. a = pH 6.8 vs pH 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.01); b = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); c = pH 7.8 vs pH 6.8, 7.4 ( P < 0.001); pH 6.8 vs pH 7.4 ( P < 0.05).

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: Cell Culture, Standard Deviation

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: Cytotoxicity of statins to C2C12 cells after 72 hours of treatment in medium of different pH. Data are presented as mean ± SD of 3 experiments, 8 replicates per experiment

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:

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: Effect of pravastatin lactone (PVL) and pravastatin hydroxy acid (PVA) on lactate dehydrogenase (LDH) release from undifferentiated and differentiated C2C12 cells maintained under different pH levels. C2C12 cells were cultured at a density of 4,000 cells/well and allowed to attach for 24 hours or to differentiate for 4 days, then exposed to increasing concentrations of PVL or PVA under acidic, neutral, and alkaline medium pH. Undifferentiated cells were treated for 72 hours, whereas differentiated cells were maintained for 24 hours. Data are presented as mean ± standard deviation, (n = 3) and analyzed by 2-way analysis of variance followed by Bonferroni's post hoc test. ( A ) LDH release from undifferentiated C2C12 cells treated with PVL. a = pH 7.4 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); e = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( B ) LDH release from differentiated C2C12 cells treated with PVL. a = pH 6.8 vs pH 7.4, 7.8 ( P < 0.01); b = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05). ( C ) LDH release from undifferentiated C2C12 cells treated with PVA. a = pH 6.8 vs pH 7.8 ( P < 0.05); b = pH 6.8 vs pH 7.4 ( P < 0.01); pH 6.8 vs pH 7.8 ( P < 0.001); c = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); d = pH 6.8 vs pH 7.4, 7.8 ( P < 0.001); pH 7.4 vs pH 7.8 ( P < 0.05); e = pH 6.8 vs pH 7.4, 7.8; pH 7.4 vs pH 7.8 ( P < 0.001). ( D ) LDH release from differentiated C2C12 cells treated with PVA. a = pH 6.8 vs pH 7.8 (P < 0.05).

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: Cell Culture, Standard Deviation

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: Intraday and interday precision and accuracy of HPLC methods used for determination of statins in human plasma samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

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: Clinical Proteomics, Concentration Assay, Control

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: Intraday and interday precision and accuracy of HPLC methods used for determination statins in PBS samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

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: Concentration Assay, Control

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: Intraday and interday precision and accuracy of HPLC methods used for determination of statins in DMEM culture medium samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

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: Concentration Assay, Control

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: Intraday and interday precision and accuracy of LC MS/MS methods used for determination of statins in cell lysate samples. Both intraday and interday assay variability values were within acceptance criteria for all tested compounds at the 4 QC levels

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: Concentration Assay, Control

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: Extraction recovery (%) of statins from human plasma, PBS, and DMEM samples

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: Extraction, Clinical Proteomics, Control