Vortioxetine reduced the expression of the Ngf gene and oxidative stress markers in knee tissue of MIA-injected rats
Intra-articular injection of MIA significantly increased Ngf mRNA levels compared to saline-injected groups (post-hoc P ≤ 0.010; Figure 4). The level of Il-1β mRNA was also increased, but only reached significance criteria in males (post-hoc P = 0.048 for males, P = 0.150 for females; Figure 4). The level ofTnf-α mRNA expression was not significantly increased (post-hoc P ≥ 0.420; Figure 4).
Vortioxetine (2 mg/kg/day for 28 days) significantly reduced NgfmRNA levels in knee tissue compared to the MIA control (post-hoc P ≤ 0.030; Figure 4). The reduction was more than 3-fold, and the vortioxetine-treated animals had similar Ngf mRNA expression to that observed in healthy animals (saline control). In contrast, duloxetine (15 mg/kg/day for 28 days) did not significantly reduceNgf gene expression (post-hoc P ≥ 0.110; Figure 4). The responses to vortioxetine and duloxetine on Ngf gene expression followed the same pattern in both sexes.
Intra-articular injection of MIA led to an increase in all measured pro-oxidants (TOS, O2•-, PAB) and oxidative products of their action (AOPP and MDA) in knee tissue compared to the sham groups (all post-hoc P ≤ 0.010; Figure 5). Oxidative stress was more pronounced in male rats, as O2•-, PAB and AOPP levels were significantly higher in MIA-injected males than in females (allpost-hoc P ≤ 0.020; Table 1).
Prolonged 28-day administration of vortioxetine (2 and 10 mg/kg/day) significantly reduced levels of all monitored oxidative stress parameters in female rats at one or both doses tested (allpost-hoc P ≤ 0.040; Figure 5B), with a trend toward dose dependence for most parameters. It was less effective in reducing oxidative stress in males and significantly suppressed only O2•-, PAB and MDA (all post-hocP ≤ 0.043; Figure 5A). Duloxetine (15 and 25 mg/kg/day for 28 days) only reduced MDA level in lower examined dose in females (allP ≤ 0.043; Figure 5B) and was without effect on oxidative stress parameters in males (all P ≥ 0.077; Figure 5A).