Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson’s Disease Model

Figure 4

In vitro experimental models with reduced mitochondrial function exhibit higher resistance to PQ, and CP protects against dopaminergic neuronal loss in the MPTP-induced PD mouse model. (a, b) To confirm the mitochondrial dependence of PQ and the additional protective effects of CP, we examined the survival rates of wild-type Rho+ and mtDNA-deficient Rho0 cells following treatment with PQ or PQ plus CP. (a) Viability of Rho+ and Rho0 cell lines after treatment with 10 μg/ml CP and PQ was confirmed using CCK8 assays (). (b) Bar graphs showing quantification of cell viability following treatment with 2 mM PQ (). (c, d) Treatment with the mitochondrial complex I inhibitor, rotenone, decreased mitochondrial function and cell viability, as confirmed by PQ treatment in SN4741 cells. (c) Cell viability, determined using CCK8 assays (). (d) Bar graphs showing quantification of cell viability in 800 μM PQ (). (f–h) MPTP and CP treatment conditions used in MPTP-induced PD mouse model experiments (). (e) A schematic overview of the protective role of CP against PQ-induced neuronal cell loss on the basis of our results. (f) Mice were administered MPTP four times per day and CP (50 mg/kg) was orally administered three times. One week after MPTP administration, mice were sacrificed and the brain tissue was immunostained. (g) Dopaminergic neurons in the SNpc and striatum regions in brain tissue from MPTP-induced PD mouse models were confirmed by TH immunostaining () (scale bars, left panel; 100 μm; right panel; 250 μm). (h, i) Bar graph showing quantification of the total number of dopaminergic neurons in the striatum region (). All data are representative of three independent experiments. by one-way ANOVA in (c, e) and by 2-tailed unpaired Student’s -test in (h, i); ns: not significant. Error bars represent +SD.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)