The effect of tacrolimus-containing polyethylene glycol-modified maghemite nanospheres on reducing oxidative stress and accelerating the healing spinal cord injury of rats based on increasing M2 macrophages

Abstract

One of the key factors in repairing spinal cord injury is reducing inflammation and oxidative stress. So, it was tried to increase the growth of neurons more rapidly by enhancing the macrophage M2 and reducing the M1 to M2 ratio by using the possible role of tacrolimus (TAC) loaded on polyethylene glycol-modified maghemite nanospheres (PEG-MNs). In this regard, after designing PEG-MNs-TAC in a three-step process and examining their properties through TEM, DLS and XRD analyses. A toxicity assay was then performed by using MTT test. To investigate the healing role of TAC on damaged tissue, a rat model was used to induce injury in vertebral T6 through physical injury. Then, rats were allocated into five groups: negative control, MNs, PEG-MNs , TAC (and PEG-MNs-TAC. Next, motor scale index, behavioral test, macrophage markers expression, concentration of IL-6, IL-2 and TNF-α, and oxidative stress on rats were analyzed. The results revealed that TAC and PEG-MNs-TAC significantly improved mobility and neuropathic tests. Furthermore, the decrease in TNF-α, IL-6, and IL-2 along with the decrease in ROS levels in the injured spinal cord were considerable in both TAC- and PEG-MNs-TAC-treated groups. Nonetheless, the PEG-MNs-TAC exposed more favorable outcomes compared to TAC. Overall, PEG-MNs-TAC could provide a new treatment for damaged spinal cord care by reducing oxidative stress and decreasing M1 to M2 ratio.

Keywords

• Spinal cord injury
• Tacrolimus
• Maghemite nanosphere
• Oxidative stress
• Macrophages