Effect of Ibuprofen, Paracetamol and Their Combination on Radical Oxygen Species (ROS) Production

The Effect of Ibuprofen, Paracetamol and Their Combination on Reactive Oxygen Species (ROS)- Production in Leukocytes and Platelet Activation

The purpose of this study is to determine whether paracetamol, ibuprofen or their combination can modify generation of radical oxygen species (ROS) from stimulated neutrophils.

Non-steroidal anti-inflammatory drugs (NSAID) are used to alleviate clinical inflammatory symptoms (e.g. pain, swelling and reduced function). Leukocytes, upon activation during inflammatory states, generate radical oxygen species (ROS) which primarily are intended for host defence against invading pathogens. Certain NSAID can modify the generation of ROS from stimulated neutrophils ranging form increased production to reduced production. Preliminary experiments in our laboratory have shown that different NSAIDs have opposing effects on the ability of leukocytes (granulocytes and monocytes) to produce ROS upon a standardized stimulus, i.e. phorbol myristate acetate (PMA). Paracetamol has a marked inhibitory effect and ibuprofen has a facilitating effect on ROS production. An inhibitory effect of paracetamol was also seen when examining platelet activation markers, whereas acetylsalicylic acid showed a clear enhancing effect in this respect. We want to examine if intake of paracetamol or ibuprofen in vivo have similar effects on leukocyte ROS production and platelet activation, respectively.

Inclusion Criteria:

• Volunteers of both sexes (ASA type I).
• Females who are not pregnant or plan conception. (A pregnancy test will be conducted before each test day)
• Persons who have not used analgesics for 3 days prior to the blood sampling.
• Persons without known active peptic ulcer or gastrointestinal bleeding.
• Persons without any known hypersensitivity for NSAIDs.
• Persons under no other drug treatment than contraceptives.
• Age 18 to 35 years of Caucasian origin

Exclusion Criteria:

• Pregnancy during the test period.
• Development of active peptic ulcer during the test period.
• Change in medication status during the test period (after inclusion).