LOW-DOSE GLUTATHIONE ADMINISTRATION IN THE PREVENTION OF CISPLATIN-INDUCED PERIPHERAL NEUROPATHY IN RATS

So far various drugs have been used in an attempt to prevent or reduce cisplatin (CDDP)-induced peripheral neuropathy. Of those tried reduce d glutathione (GSH) is one of the most promising. Ifs effectiveness ha s already been demonstrated by means of morphological methods in CDDP- treated rats in which high doses of GSH (up to 1200 mg/kg) were given. In the current study neurophysiological and morphological methods wer e used to evaluate the effect of low doses (150-300 mg/kg) of GSH i.p. on the peripheral nervous system of the rat. Four groups of 8 female Wistar rats were treated as follows: (A) CDDP 2 mg/kg i.p. weekly for 9 courses; (B) same as (A) plus GSH 150 mg/kg i.p. weekly; (C) same as (A) plus GSH 300 mg/kg i.p. weekly; (D) same as (A) plus GSH 150 mg/k g i.p. on the day of DDP injection followed by 150 mg/kg day over the next 2 days. Eleven age-matched untreated rats were used as controls. Sensory conduction velocity was recorded in the tail nerve and morphol ogic and morphometric examinations were performed on the dorsal roof g anglia neurons (L4-L6) in each animal. The results demonstrated that t he neurophysiological and pathological changes induced by CDDP adminis tration were less severe in rats co-treated with GSH. No significant d ifferences could be related to the 3 different regimens of GSH co-trea tments. This experiment confirms that GSH is able to reduce the neurot oxicity of CDDP and that it is effective even at doses as low as those used in the present study. (C) 1994 Intox Press, Inc.