Protective effects of glutathione on cisplatin neurotoxicity in rats.
OBJECTIVE
Different attempts have been made to minimize the neurotoxicity of cisplatin (DDP) and the use of "neuroprotective" drugs seems to be a promising strategy. In rats we compared the effects on the dorsal root ganglia neurons and peripheral nerves of the administration of DDP alone or in combination with glutathione (GSH), a putative "neuroprotective" drug.


METHODS
Twenty-four Wistar rats were treated with DDP alone (2 mg/kg/week) or with the same dose of DDP plus GSH (300 mg/week) for nine cycles and they were compared to 12 untreated age-matched rats. All the animals underwent either neurophysiological examination of the tail nerve or pathologic examination of the dorsal root ganglia. Analytical determination of the platinum concentration in dorsal root ganglia was also performed.


RESULTS
Morphologic and morphometric evaluations demonstrated a reduced incidence of pathologic changes in DDP plus GSH-treated rats with respect to DDP-treated ones. In agreement with the morphological findings, the platinum concentration in the dorsal root ganglia was lower and sensory nerve conduction velocity in the tail nerve less markedly decreased in the animals treated with DDP plus GSH with respect to those treated with DDP alone.


CONCLUSIONS
We conclude that the administration of GSH is effective in reducing the neurotoxic effects of DDP, thus supporting the preliminary results obtained in clinical trials in humans.
Institute of Human Anatomy, University of Milan, Italy.
G
G
Cavaletti
C
C
Minoia
M
M
Schieppati
G
G
Tredici
D000818:Animals; D002945:Cisplatin / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000627:therapeutic use*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D010984:Platinum / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D010984:Platinum; D005978:Glutathione; D002945:Cisplatin