Mroué Mohamad, Bessaguet Flavien, Nizou Angélique, Richard Laurence, Sturtz Franck, Magy Laurent, Bourthoumieu Sylvie, Danigo Aurore, Demiot Claire
UR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, France.
UMR INSERM 1083 CNRS 6015 MITOVASC Laboratory, CarMe Team, University of Angers, 49045 Angers, France.
Pharmaceutics. 2024 Jan 20;16(1):139. doi: 10.3390/pharmaceutics16010139.
The occurrence of neuropathic pain in chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting effect of many commonly-used anticancer agents. Polyvalent human immunoglobulins (hIg), used in the treatment of several peripheral neuropathies, may alleviate neuropathic pain. The aim of this project was to investigate the preventive effect of hIg in two mouse models of CIPN, induced by vincristine (VCR, 100 µg/kg/d) and oxaliplatin (OXP, 6 mg/kg/3d). Human Ig were administered one day before the first injection of chemotherapy. The onset of CIPN and effects of hIg were assessed via functional tests and morphological analyses of sensory nerves. To evaluate the effect of hIg on chemotherapy cytotoxicity, viability assays were performed using hIg (0 to 12 mg/mL) combined with anticancer agents on human cancer cell lines. The preventive treatment with hIg alleviated tactile hypersensitivity and nerve injuries induced by VCR. It also alleviated tactile/cold hypersensitivities and nerve injuries induced by OXP. Treatment with hIg did not affect the cytotoxicity of either chemotherapy. Furthermore, in combination with VCR, hIg potentiated chemo-induced cell death. In conclusion, hIg is a promising therapy to prevent the onset of CIPN and potentiate chemotherapy effect on cancer, reinforcing the interest in hIg in the management of CIPN.
化疗诱导的周围神经病变(CIPN)中神经性疼痛的发生是许多常用抗癌药物的主要剂量限制效应。用于治疗多种周围神经病变的多价人免疫球蛋白(hIg)可能会减轻神经性疼痛。本项目的目的是研究hIg在两种由长春新碱(VCR,100μg/kg/天)和奥沙利铂(OXP,6mg/kg/3天)诱导的CIPN小鼠模型中的预防作用。在首次注射化疗药物前一天给予人免疫球蛋白。通过感觉神经的功能测试和形态学分析评估CIPN的发病情况和hIg的作用。为了评估hIg对化疗细胞毒性的影响,使用hIg(0至12mg/mL)与抗癌药物联合作用于人癌细胞系进行活力测定。hIg预防性治疗减轻了VCR诱导的触觉超敏反应和神经损伤。它还减轻了OXP诱导的触觉/冷超敏反应和神经损伤。hIg治疗不影响任何一种化疗的细胞毒性。此外,与VCR联合使用时,hIg增强了化疗诱导的细胞死亡。总之,hIg是一种有前景的预防CIPN发病并增强化疗对癌症疗效的疗法,这增强了人们对hIg在CIPN管理中的兴趣。