Arthritis develops in DBA/1xB10A(4R) mice and Wistar rats upon intraplantar injection of
potassium peroxochromate (K3CrO8), and is here quantified by whole blood chemiluminescence (CL) and 99mpertechnetate-imaging (99mTcO4-), and related to overt disease symptoms (the
arthritis index). During the aqueous decay of K3CrO8 to
chromate (VI), the
chromium(V)-bound
oxygen is released as
superoxide,
hydroxyl radicals,
singlet oxygen and
hydrogen peroxide, the same reactants, which are produced by activated phagocytes during
inflammation.
Reactive oxygen species (ROS) trigger the breakdown of the sulfhydryl-dependent
antioxidant defence system and induce the
nuclear factor kappa B-dependent expression of pro-inflammatory
cytokines, which prime phagocytic
NADPH oxidases to the enhanced production of ROS. During both the acute inflammatory response and the onset of the secondary response in non-injected paws, the phorbolester-stimulated ROS production of phagocytes was significantly enhanced (p < 0.001) and correlated well to the
arthritis index (r = 0.797) and the uptake of 99mTcO4- into inflamed joints.
Chromate(VI), formed during the decay of K3CrO8, contributes to the progression of
arthritis by inhibition of
glutathione reductase, thereby increasing intracellular H2O2 concentrations. In addition,
Cr(VI) reduced to Cr(V) by ascorbate, catalyzes
hydroxyl radical production in the presence of
hydrogen peroxide. A stable loop forms, in which ROS, continuously produced by
Cr(VI)/Cr(V) redox-cycling, drive the primary response into chronic self-perpetuating
inflammation. We see the main application of K3CrO8-induced
arthritis and its assessment by both 99mTcO4- imaging and chemiluminescent immunosensoring of phagocytic activity in unseparated blood as for the rapid screening of novel
anti-rheumatic drugs and treatments.