The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

Abstract

Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may
also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may
originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins.
When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of
free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have
diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has
been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of
oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from
oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and
their measurement therefore offers a way to assess oxidative stress. Elevated levels of F₂-isoprostanes have
also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large
amounts of bioactive F₂-isoprostanes are excreted in the urine in normal basal situations, with a wide
interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs
to be explored further. Current understanding suggests that measurement of F₂-isoprostanes in body fluids
provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory
conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging
properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific
tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid.