Ozone
Preconditioning Protects against
Rotenone-Induced Neurodegeneration
in Rats
A.M.
Shehata,
L.
Re,
O.M.
Yousef
SUMMARY - Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. However, a low physiologically relevant concentration of reactive oxygen species could be useful and essential to regulate a variety of key molecular mechanisms. Rotenone exposure has been reported to produce an in vivo experimental model of Parkinson’s disease (PD) by inhibiting mitochondrial function and eliciting oxidative stress. This study evaluated ozone preconditioning (OP) on an in vivo model of rotenone-induced neuro-degeneration in rats. Rotenone was injected s.c. at a dose of 2 mg/kg every other day up to six injections for a total period of 11 days. Daily ozone preconditioning (7 mg/kg/day, 5 days/week) preceded rotenone treatment by two weeks and continued with rotenone treatment for a period of 11 days. The neurochemical effect was evaluated by measuring the transmitters dopamine (DA) and norepinehrine (NE), and the levels of oxidative stress parameters including nitric oxide as total nitrite and nitrate (NO) and reduced and oxidized glutathione, the enzymatic activity of total superoxide dismutase (SOD), malondialdehyde (MDA), protein carbonyls and adenosine triphosphate (ATP) in specific brain areas of the treated animals. In addition, the histopathological changes to brain tissues of different groups were studied. The present results showed that subchronic treatment of rotenone significantly reduced the levels of DA and NE in both the cortical and striatal regions. In addition, rotenone treatment significantly increased the levels of nitric oxide, induced lipid and protein peroxidation in terms of increased levels of MDA and protein carbonyls, but decreased the levels of ATP and the reduced glutathione (GSH) and caused noticeable histological abnormalities in the tested brain areas. Ozone exposure moderately elevated MDA and protein carbonyls and decreased GSH indicating the occurrence of a mild oxidative stress. In addition, ozone remarkably increased ATP, DA and NE levels and did not induce any histological abnormalities in the tested brain areas. On the other hand, ozone preconditioning significantly protected the cortex and striatum against rotenone-induced transmitters depletion and mitochondrial dysfunction and prevented rotenone–induced structural deformity.