Bioenergetic study of murine hepatic tissue treated in vitro with atorvastatin

BMC Clinical Pharmacology

Abdul-Kader Souid³  Alia Albawardi¹  Saeeda Almarzooqi¹  Bayan Al-Dabbagh²  Ali S Alfazari² 

[1] Department of Pathology, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates;Department of Internal Medicine, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates;Department of Pediatrics, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates

关键词: Apoptosis;    Caspases;    Respiration;    Mitochondria;    Statins;   

Others  :  860631
DOI  :  10.1186/2050-6511-14-15

 received in 2012-12-26, accepted in 2013-02-22,  发布年份 2013

【 摘 要 】

Atorvastatin (a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor) is a widely used cholesterol-lowering drug, which is recognized for its potential hepatotoxicity. This study investigated in vitro effects of this agent on hepatic tissue respiration, ATP content, caspase activity, urea synthesis and histology. Liver fragments from Taylor Outbred and C57Bl/6 mice were incubated at 37°C in Krebs-Henseleit buffer continuously gassed with 95% O₂: 5% CO₂ in the presence and absence of atorvastatin. Phosphorescence O₂ analyzer that measured dissolved [O₂] as a function of time was used to monitor cellular mitochondrial O₂ consumption. The caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin was used to monitor caspase activity. The rates of hepatocyte respiration (μM O₂ min^-1 mg^-1) in untreated samples were 0.15 ± 0.07 (n = 31). The corresponding rates for samples treated with 50 nM (therapeutic concentration), 150 nM or 1.0 μM atorvastatin for ≤13 h were 0.13 ± 0.05 (n = 19), p = 0.521. The contents of hepatocyte ATP (pmol^-1 mg^-1) in untreated samples were 40.3 ± 14.0 and in samples treated with 1.0 μM atorvastatin for ≤4.5 h were 48.7 ± 23.9 (p = 0.7754). The concentrations of urea (mg/dL mg^-1, produced over 50 min) for untreated samples were 0.061 ± 0.020 (n = 6) and for samples treated with 1.0 μM atorvastatin for ≤6 h were 0.072 ± 0.022 (n = 6), p = 0.3866. Steadily, hepatocyte caspase activity and histology were unaffected by treatments with up to 1.0 μM atorvastatin for ≤6 h. Thus, the studied murine model showed preserved hepatocyte function and structure in the presence of high concentrations of atorvastatin.

【 授权许可】

   
2013 Alfazari et al.; licensee BioMed Central Ltd.

【 图 表 】

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