Adriamycin (ADR) is a chemotherapeutic for the treatment of solid
tumors. This
quinone-containing
anthracycline is well known to produce large amounts of
reactive oxygen species (ROS) in vivo. A common complaint of patients undergoing long-term treatment with ADR is
somnolence, often referred to as "
chemobrain." While ADR itself does not cross the blood brain barrier (BBB), we recently showed that ADR administration causes a peripheral increase in
tumor necrosis factor alpha (
TNF-alpha), which migrates across the BBB and leads to
inflammation and oxidative stress in brain, most likely contributing to the observed decline in cognition. In the current study, we measured levels of the
antioxidant glutathione (GSH) in brains of mice injected intraparitoneally (i.p.) with ADR, as well as the levels and activities of several
enzymes involved in brain GSH metabolism. We observed significantly decreased GSH levels, as well as altered GSH/
GSSG ratio in brains of ADR treated mice relative to saline-treated controls. Also observed in brains of ADR treated mice were increased levels of
glutathione peroxidase (GPx),
glutathione-S-transferase (GST), and
glutathione reductase (GR). We also observed increased activity of GPx, but a significant reduction in GST and GR activity in mice brain, 72 h post i.p. injection of ADR (20 mg/kg
body weight). Furthermore, we used redox proteomics to identify specific
proteins that are oxidized and/or have differential levels in mice brains as a result of a single i.p. injection of ADR.
Visinin like protein 1 (VLP1), peptidyl
prolyl isomerase 1 (Pin1), and
syntaxin 1 (SYNT1) showed differential levels in ADR treated mice relative to saline-treated controls.
Triose phosphate isomerase (TPI),
enolase, and
peroxiredoxin 1 (PRX-1) showed significantly increased specific carbonylation in ADR treated mice brain. These results further support the notion ADR induces oxidative stress in brain despite not crossing the BBB, and that
antioxidant intervention may prevent ADR-induced
cognitive dysfunction.