Introduction: Taxanes are a wide group of anticancer drugs. Paclitaxel (PTX) induced peripheral neuropathy is the main long-lasting side effect of paclitaxel. This harmful impact has a significant NLRP3 inflammasome pathway integration. Vitamin B12 combined with BMMSCs may have an alleviating role.
Objectives: This study aims to assess the possible synergistic influence of vitamin B12 and bone marrow mesenchymal stem cells (BMMSCs) to alleviate sciatic neuropathy and define the related anti-NLRP3 inflammasome pathway role.
Study design: About 50 adult albino rats were allocated into 5 groups. Group I (control): no treatments, group II treated with paclitaxel (PTX neuropathy): injected (i.p) with PTX (2.0 mg kg−1) on days 1, 3, 5, and 8, group III (PTX+ vit B12): was treated as group II, then on day 10 rats were injected with vit B12 (10 mg /kg) per every other day (i.m) for 28 days, group IV (PTX+MSCs) as group II, then on day 10, injected (i.v) with a single dose of BMMSCs (1x106 cells) in 1.0 ml saline. Finally, group V (PTX + vit B12+ MSCs) was treated as group II, then injected with vitamin B12 and BMMSCs at the same doses mentioned before. After sacrificing, sciatic samples were collected, processed, and examined histopathologically, immunohistochemically, and with the electron microscope.
Results: PTX group showed marked histological distortion, congested vasculature, decreased Schwann cells, degenerated fibers, vacuolated axons, upregulated CD68, NLRP3, and caspase-1 immunomarkers. PTX+ vit B12 group showed mild histological improvement, and mild downregulated CD68, NLRP3, and caspase-1 immunomarkers. PTX+MSCs group showed moderate histological improvement and moderate downregulated CD68, NLRP3, and caspase-1 immunomarkers. PTX+ vit B12+ MSCs showed apparent histological improvement, the myelinated fibers appeared nearly normal with apparent downregulated CD68, NLRP3, and caspase1 immunomarkers.
Conclusion: Combined vitamin B12 and BMMSCs therapy synergistically alleviated PTX-neuropathy with obvious NLRP3 inflammasome pathway inhibition.