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.