Neurotropin reverses paclitaxel-induced neuropathy without affecting anti-tumour efficacy

Mechanical allodynia in the Von Frey test in rats. Rats were treated with paclitaxel (PTX, 6mg/kg, i.p.) once a week for 4 weeks. Neurotropin (NTP, 200 NU/kg) was administered orally three times a week for 4 weeks. Results are expressed as mean ± SEM of 7–8 animals on Days 0, 10, and 24. ††P<0.01 compared with vehicle, ∗∗P<0.01 compared with PTX alone.

Cold hyperalgesia in the acetone test in rats. Rats were treated with paclitaxel (PTX, 6mg/kg, i.p.) once a week for 4 weeks. Neurotropin (NTP, 200 NU/kg) was administered orally three times a week for 4 weeks. Results are expressed as mean ± SEM of 7–9 animals. ††P<0.01 compared with vehicle, ∗∗P<0.01 compared with PTX alone.

Motor functions in the grip strength (A) and balance beam (B) tests. Rats were treated with paclitaxel (PTX, 6mg/kg, i.p.) once a week for 4 weeks. Neurotropin (NTP, 200 NU/kg) was administered orally three times a week for 4 weeks. Results are expressed as mean ± SEM of 8–9 animals. ††P<0.01 compared with vehicle, ∗∗P<0.01 compared with PTX alone.

Effect of neurotropin (NTP) on neurite degeneration induced by paclitaxel (PTX) in PC12 cells. PC12 cells were incubated with PTX (10ng/ml) for 24h (A) or 168h (B) in the presence or absence of various concentrations of NTP. The neurite lengths were measured using image analysis software (Image J 1.36). Results are expressed as mean ± SEM (n=4). ††P<0.01 compared with control, ∗P<0.05, ∗∗P<0.01 compared with PTX alone.

Effect of neurotropin (NTP) on neurite degeneration induced by paclitaxel (PTX) in rat DRG neurons. Primary cultured DRG neurons were incubated with PTX (10ng/ml) for 24h (A) or 168h (B) in the presence or absence of various concentrations of NTP. The neurite lengths were measured using image analysis software (Image J 1.36). Results are expressed as mean ± SEM (n=4). †P<0.05, ††P<0.01 compared with control, ∗P<0.05 compared with PTX alone.

Effect of neurotropin (NTP) on histological change induced by paclitaxel (PTX) in rat sciatic nerve. Rats were treated with paclitaxel (PTX, 6mg/kg, i.p.) once a week for 4 weeks. Neurotropin (NTP, 200 NU/kg) was administered orally three times a week for 4 weeks. On Day 25, the sciatic nerve was harvested, and samples were stained with toluidine blue. Photographs were originally magnified 800 ×. Scale bar 50 μm.

Effect of neurotropin (NTP) on microtubule aggregates induced by paclitaxel (PTX). Walker 256 (A) and A549 cells (B) were incubated with PTX (10ng/ml) for 24h in the presence or absence of NTP (0.03 NU/ml). Cells were immunostained with beta tubulin for imaging of microtubule aggregates. The arrows indicate beta tubulin. Photographs were originally magnified 400 ×. Scale bar, 100 μm.

Effect of neurotropin (NTP) on the tumour cytotoxicity of paclitaxel (PTX). Walker 256 (A) and A549 cells (B) were incubated with PTX (10ng/ml) for 6, 12, 24, 48, or 72h in the presence or absence of various concentrations of NTP. Cell viability was measured by WST-8 assay. Results are expressed as percentages of the viability of the vehicle-treated group (n=4).

Effect of neurotropin (NTP) on the anti-tumour effect of paclitaxel (PTX). The LLC cells-implanted mice were treated with paclitaxel (PTX, 6mg/kg, i.p.) and neurotropin (NTP, 600 NU/kg, p.o.) once a day for 12 days. Results are expressed as mean ± SEM of 8–10 animals on Days 3, 6, 9, 12, 15 and 18. †P<0.05, ††P<0.01 compared with vehicle.