Quantitative detection of targeted neurotransmitters in dorsal root ganglia in rats with chronic peripheral neurotoxicity caused by oxaliplatin

Abstract

Objective To observe the effects of oxaliplatin on the concentration of neurotransmitters in dorsal root ganglia in a rat model of chronic peripheral neurotoxicity. Methods A total of 24 male SD rats (SPF grade) were randomly divided into model group and normal control group (n=12 in each group). The model of chronic peripheral neurotoxicity was established by multiple cumulative doses and multiple intraperitoneal injections (cumulative dose of 48 mg/m2, simulated human dose > 1 200 mg/m2). The neurotransmitters with significant concentration changes in the dorsal root were screened out by a quantitative detection. Results At a cumulative dose of 48 mg/m2 oxaliplatin, a rat model of chronic peripheral neurotoxicity was established successfully. In the dorsal root, the neurotransmitters with obviously increase in concentration were L-glutamine (58.54±10.46 nmol/L, P < 0.05), L-glutamic acid (43.12±7.76 nmol/L, P < 0.05), dopamine (0.03±0.02 nmol/L, P < 0.01), norepinephrine (0.25±0.04 nmol/L, P < 0.05), 3、4-dihydroxyphenylacetic acid (0.41±0.01 nmol/L, P < 0.01), and vanillylmandelic acid (3.30±0.63 nmol/L, P < 0.05) when compared with the normal control group. Among them, dopamine and its metabolite 3、4-dihydroxyphenylacetic acid were the most significant. Conclusion Chronic accumulation of oxaliplatin can cause changes in the concentration of neurotransmitters in the dorsal root ganglia, which may be related to neuronal damage and chronic peripheral neurotoxicity.

Keywords

• oxaliplatin
• chronic peripheral neurotoxicity
• dorsal root ganglion
• neurotransmitters