engleski

Influence of small doses of various vehicles on acetaminophen induced liver injury

Organic solvents or detergents are used in biological studies to facilitate solution of drugs with low solubility. Although they are generally thought of as being relatively inert, they can induce effects that are often overlooked. Inadequate usage of vehicles is the leading cause of artifacts in acetaminophen induced liver injury (AILI) investigations. Therefore, we decided to investigate the effect of dimethylsulfoxide (DMSO), dimethylformamide (DMF), propylene glycol (PG), ethanol (ETOH) and Tween20 on AILI. 57BL/6 male mice received intraperitoneally (i.p.) 30 minutes before acetaminophen (300 mg/kg, i.p., in warm saline) injection of saline, DMSO, DMF, PG or Tween 20, at 0, 6 mL/kg or 0, 2 mL/kg. Control groups received only vehicle. After seven hours blood and livers were taken for analysis. Alanine aminotransferase levels (ALT) in plasma and reduced glutathione (GSH) levels in liver were determined and histopatological slides were evaluated. DMSO and DMF (both doses) almost completely abolished AILI. PG (0, 6 mL/kg) was also protective, but the dose of 0.2 mL/kg was only partially effective. These three solvent blocked acetaminophen induced GSH depletion. ETOH (0, 6 mL/kg) was partially effective, while the dose of 0, 2 mL/kg and TWEEN 20 (both doses) had no influence. In control groups DMF (0, 6 mL/kg) slightly decreased GSH levels, while the dose of 0, 2 mL/kg and any other vehicle had no significant influence on GSH or ALT levels. None of the vehicles was protective in model of liver injury caused by D-galactosamine and lipopolysaccharide. Extreme caution is needed when organic solvents are used in AILI investigations.

acetaminophen; dimethylsulfoxide; dimethylformamide; propylene glycol; ethanol; liver injury

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