L-THP ameliorated OXA-induced neurotoxicity and reduced platinum
accumulation in DRG of mice
To further confirm whether L-THP could attenuate OXA-induced
neurotoxicity in vivo , we performed a behavioural test and
detected platinum accumulation in DRG in OXA-treated mice without or
with L-THP co-treatment. As shown in Figure 6 , 24 h after the
final administration, the sensitivity to cold stimulation, expressed as
the frequency of hind-paw licking in the mice treated with OXA (8 mg/kg,
iv), was approximately 3 folds that in the vehicle-treated male or
female mice. L-THP (5~20 mg/kg) dose-dependently
attenuated the increase in OXA-induced cold-stimulation sensitivity
(Figure 6a and 6b ). Accordingly, the concentration of platinum
in the DRG reached
2.35
ng/mg in mice treated with OXA (8 mg/kg), while L-THP reduced the
concentration of platinum in the DRG in a dose-dependent (5-20 mg/kg)
manner (Figure 6c ). The L-THP-alone group and the vehicle-alone
group did not show a significant difference in cold-stimulation
sensitivity, indicating that the abirritation of L-THP could be
excluded. Therefore, L-THP ameliorated OXA-induced peripheral
neurotoxicity by inhibiting the uptake of OXA in DRG cells rather than
by abirritation.