Fig. 4. Creatine, CoQ10 or their combination blocks 3-NP-induced impairment of striatal glutathione homeostasis and reduces oxidative damage.
The striatum and cortex tissues collected from the Lewis rats described in methods were used for analysis of glutathione metabolites and oxidative damage markers. A. 3-NP administration resulted in a statistically significant reduction of striatal levels of GSH and the ratio of GSH/GSSG, whereas levels of GSSG were not significantly affected by 3-NP treatment measured by HPLC. Creatine, CoQ10 or the combination diet treatment significantly blocked 3-NP induced reductions in striatal levels of GSH and the ratio GSH/GSSG without impacting the GSSG levels. The combination diet exerted an additive effect in preserving striatal GSH/GSSG ratio. B. HPLC analysis of MDA levels in striatum revealed a statistically significant increase in MDA levels in 3-NP intoxicated rats treated with control diet. Creatine, CoQ10 or the combination diet treatment significantly reduced 3-NP-induced MDA formation in the striatum with the combination exerting a more significant reduction in striatal MDA. C. HPLC analysis of the ratio of 8OH2dG over dG, a marker of DNA oxidation, showed a significant increase in oxidative DNA damage in the cerebral cortex following 3-NP treatment, which is attenuated by treatment of creatine, CoQ10 or the combination diet, with the combination treatment reaching a statistically significant attenuation. Data represent mean ± SEM. *p< 0.05, ** p< 0.01 compared to control alone; #p< 0.05, ##p< 0.01 compared to 3-NP with control diet; + p< 0.05 compared to 3-NP with either creatine or CoQ10 diet, by ANOVA. n= 15 rats per group.