Molecular mechanism of electroacupuncture treatment on oxaliplatin-induced peripheral neurotoxicity in rats

Abstract

Oxaliplatin (L-OHP) has been widely used in the treatment of various tumors, especially in colorectal cancer. The mechanism of peripheral neurotoxicity induced by L-OHP (OIPN) is unclear and current therapeutic options only serve to alleviate the symptoms rather than prevent OIPN. To observe the effects of electroacupuncture (EA) stimulation on OIPN in rats, rats were randomly divided into the control group, OIPN model group, and OIPN + EA group. To establish OIPN rat models, a single intraperitoneal injection with 10 mg/kg L-OHP in the OIPN model rats. Rats in the control group received a single intraperitoneal injection with 0.9% lactose. From the third day after establishing OIPN models, the rats were treated with EA. Cold allodynia and heat sensitivity were assessed using the acetone drop and the Hargreaves method, respectively. Pathological changes in nerves were detected using hematoxylin and eosin (H&E) staining and transmission electron microscopy. Related mRNA and protein expression levels were measured by real-time polymerase chain reaction (PCR) and western blotting from 14 days after establishing OIPN models. Our results showed that L-OHP significantly increased the sensitivity to cold allodynia and nervous injury, which were ameliorated after EA treatment. The expression of glucocorticoid receptor alpha (GR-α) and B-cell lymphoma 2 (Bcl-2) was significantly decreased and that of Bax was significantly increased in sciatic nerve of OIPN model rats compared with control rats. However, EA treatment significantly inhibited L-OHP-induced protein expressions in rats. Moreover, compared with the control rats, the nucleus NF-κBp65 levels were significantly increased, while the cytoplasm NF-κBp65 levels were significantly decreased, which were reversed by EA treatment. In conclusion, EA treatment may reduce peripheral neurotoxicity induced by L-OHP through regulating related protein expression.