Ganglioside GM1 (Porcine) Ameliorates Paclitaxel-Induced Neuropathy in Rats
Vilai Chentanez MD, PhD*, Natthapaninee Thanomsridejchai MSc*, Natthara Duangmardphon MSc*, Sithiporn Agthong MD, PhD*, Atitaya Kaewsema BSc*, Thanasil Huanmanop MD, MSc*, Supang Maneesri PhD**
Affiliation : * Peripheral Nerve Research Unit, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok ** Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok
Background : Paclitaxel, an anti-neoplastic agent effective against several solid tumors, has several side
effects including peripheral neuropathy. So far, there are no effective treatments for this complication. Monosialic
acid ganglioside (GM1) has been shown to protect neurons against injuries and degeneration. However, its
efficacy in the treatment of paclitaxel-induced neuropathy has not been verified.
Objective : To evaluate the effect of porcine GM1 on neurophysiological abnormalities in rats receiving
paclitaxel.
Material and Method: Fifty-four Wistar rats were divided into control, vehicle for paclitaxel (Cremophor EL),
paclitaxel, and paclitaxel + GM1 groups. Paclitaxel 16 mg/kg/week for five consecutive weeks was given
intraperitoneally. Treatment with 30 mg/kg 5 days per week of GM1 was started 3 days prior to the first dose
and continued until 3 days after the last dose of paclitaxel. Tail and hind paw thermal thresholds including
tail motor nerve conduction velocity (MNCV) were measured prior to and after the start of treatments. Histo-
pathology of the sciatic nerve was also examined.
Results : Paclitaxel alone induced thermal hypoalgesia and reduced tail MNCV. Less severe abnormalities
were also found with the vehicle. GM1 appeared to prevent the development of hypoalgesia and ameliorated
the decreased MNCV without any evidence of Guillain-Barre Syndrome. Mild endoneurial edema and axonal
degeneration in the sciatic nerve sections were seen in paclitaxel treated rats. Microtubule accumulation and
activated Schwann cell were also presented in the paclitaxel treated groups.
Conclusion : These data suggest that porcine GM1 may be useful in the prevention and treatment of paclitaxel-
induced neuropathy. However, the adverse effect of Cremophor EL should be of concern.
Keywords : Paclitaxel, Neuropathy, Ganglioside, GM1
