Address for correspondence: Low-Tone Ho and Anya Maan-Yuh Lin, Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan. Voice: 886-2-28712121 ext. 2688; fax: 886-2-28751562.
In contrast to acute ischemia and subsequent reperfusion that
produce excess free radicals, intermittent hypoxia (IH) is reported
to play an important role in upregulation of antioxidative defensive
mechanisms. In the study we report here, the neuroprotective
effect of IH was evaluated using intraperitoneal injection of
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in ICR mice.
Adult male ICR mice were subjected to 380 mmHg in an altitude
chamber for 15 hours/day for 14 or 28 days. MPTP decreased striatal
dopamine content in normoxic mice. However, IH did not significantly
alter the MPTP-induced depletion of striatal dopamine content.
Furthermore, MPTP had no effect on GSH content but reduced GSH/GSSG
ratio in mouse striatum. IH altered neither GSH content nor
MPTP-induced reduction in GSH/GSSG ratio. Although MPTP had
no effect on striatal SOD activity in normoxic mouse, IH increased
SOD activity in the saline and MPTP groups. Neither MPTP nor
IH affected GPx in mouse striatum. Furthermore, in our
ex vivo study, both the autooxidation and iron induced lipid peroxidation
of cortical homogenates were lower in the IH-treated group than
those of the normoxic group, indicating a reduced oxidative
status after IH treatment. In conclusion, exposure to IH has
been suggested to be beneficial in preventing iron-induced oxidative
injuries in biological organisms, and our data support this
notion in that IH not only decreased iron-induced lipid peroxidation
but also increased antioxidative defense enzyme activity in
mouse brain. Furthermore, the lack of neuroprotective effect
by IH of MPTP-induced depletion of striatal dopamine content
suggests that oxidative stress may not be the only mechanism
for the MPTP-induced neurotoxicity.
