Practical value of ferroptosis inhibitor in a rat model of 6-hydroxydopamine-induced Parkinson's disease
Objective To explore the practical value of ferroptosis inhibitor in a rat model of 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Methods 16 a dult male SD rats were modulated after 1 week of adaptive feeding. PD model rats successfully modulated were randomly divided into PD group and ferroptosis inhibitor group,with 8 rats in each group. Ferroptosis inhibitor group was given 2 mg/kg ferrostatin-1 intraperitoneal injection,PD group was given equal dose of normal saline intraperitoneal injection for 14 consecutive days. Behavioral tests were performed 24 h after the last dose,and the number of healthy side rotation,escape latency and number of crossing the platform were recorded. Proper amounts of substantia nigra tissue were taken from rats after cervical dislocation execution,and the expression levels of PD-associated protein glutathione peroxidase 4 (GPX4),solute carrier family 7,member 11 (SLC7A11),oxidative stress[reactive oxygen species (ROS),glutathione (GSH),lipid peroxides (LPO),malondialdehyde (MDA)]and inflammatory markers[tumor necrosis factor-α (TNF-α),interleukin (IL)-1β,IL-6]were determined. Results The number of healthy side rotation,escape latency and number of crossing the platform of PD group were (120.31±28.50) turns,(41.72±6.59) s and (2.76±0.45) times,while those of ferroptosis inhibitor group were (78.63±11.23) turns,(24.98±5.40) s and (4.09±0.56) times. Compared with PD group,the number of healthy side rotation of rats in ferroptosis inhibitor group was reduced,the escape latency was shortened,and the number of crossing the platform was increased (P<0.05). The expression levels of GPX4 and SLC7A11 in the substantia nigra of ferroptosis inhibitor group were (2.96±0.51) and (2.25±0.35),which were higher than (2.18±0.42) and (1.76±0.20) of PD group (P<0.05). The levels of ROS,LPO,and MDA in the substantia nigra tissue homogenate of ferroptosis inhibitor group were (4.08±0.47) pg/ml,(6.54±1.09) μg/ml,and (3.26±0.42) ng/ml,which were lower than (5.21±0.67) pg/ml,(8.35±1.20) μg/ml,and (4.10±0.56) ng/ml of PD group;GSH level of ferroptosis inhibitor group was (13.24±2.89) ng/ml,which was higher than (10.18±2.30) ng/ml of PD group (P<0.05). The levels of TNF-α,IL-1β and IL-6 in the substantia nigra tissue homogenate of ferroptosis inhibitor group were (14.22±1.98),(16.29±2.75) and (6.42±0.97) pg/ml,which were lower than (18.29±2.65),(23.01±4.39) and (8.36±1.10) pg/ml of PD group (P<0.05). Conclusion Ferroptosis inhibitor can alleviate behavioral abnormalities in PD model rats induced by 6-OHDA,which is mainly related to its up-regulation of antioxidant protein expression,inhibition of oxidative stress and inflammation.
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