Ganglioside GM1 (porcine) ameliorates paclitaxel-induced neuropathy in rats.
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.


METHODS
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. Histopathology 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.


CONCLUSIONS
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.
Chentanez
Vilai
V
Peripheral Nerve Research Unit, Department ofAnatomy, Faculty of Medicine, Chulalongkorn University, Bangkok. fmedvct@md.chula.ac.th
Thanomsridejchai
Natthapaninee
N
Duangmardphon
Natthara
N
Agthong
Sithiporn
S
Kaewsema
Atitaya
A
Huanmanop
Thanasil
T
Maneesri
Supang
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000009:adverse effects / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy; D017239:Paclitaxel / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012677:Sensation / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005677:G(M1) Ganglioside; D017239:Paclitaxel