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一种治疗顺铂诱导的雄性和雌性小鼠异常性疼痛、功能障碍及情感损伤的新疗法。

A Novel Therapy for Cisplatin-Induced Allodynia and Dysfunctional and Emotional Impairments in Male and Female Mice.

作者信息

Martínez-Martel Ignacio, Pol Olga

机构信息

Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau, Sant Quintí 77-79, 08041 Barcelona, Spain.

Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.

出版信息

Antioxidants (Basel). 2023 Nov 30;12(12):2063. doi: 10.3390/antiox12122063.

Abstract

Patients undergoing chemotherapy with cisplatin (CIS) develop neuropathy in addition to other symptoms such as, anxiety, depression, muscle wasting and body weight loss. This symptomatology greatly weakens patients and may even lead to adjournment of chemotherapy. The protecting actions of molecular hydrogen in many neurological illnesses have been described, but its effect on the functional and emotional deficiencies caused by CIS has not been assessed. In C57BL/6J male and female mice injected with CIS, we examined the impact of the prophylactic treatment with hydrogen-rich water (HRW) on: (i) the tactile and cold allodynia, (ii) the deficits of grip strength and weight loss, (iii) the anxiodepressive-like behaviors and (iv) the inflammatory and oxidative reactions incited by CIS in the dorsal root ganglia (DRG) and prefrontal cortex (PFC). The results demonstrate that the mechanical allodynia and the anxiodepressive-like comportment provoked by CIS were similarly manifested in both sexes, whereas the cold allodynia, grip strength deficits and body weight loss produced by this chemotherapeutic agent were greater in female mice. Nonetheless, the prophylactic treatment with HRW prevented the allodynia and the functional and emotional impairments resulting from CIS in both sexes. This treatment also inhibited the inflammatory and oxidative responses activated by CIS in the DRG and PFC in both sexes, which might explain the therapeutic actions of HRW in male and female mice. In conclusion, this study revealed the plausible use of HRW as a new therapy for the allodynia and physical and mental impairments linked with CIS and its possible mechanism of action.

摘要

接受顺铂(CIS)化疗的患者除出现焦虑、抑郁、肌肉萎缩和体重减轻等其他症状外,还会发生神经病变。这种症状极大地削弱了患者的身体状况,甚至可能导致化疗中断。分子氢在许多神经系统疾病中的保护作用已有报道,但其对顺铂引起的功能和情绪缺陷的影响尚未评估。在注射了顺铂的C57BL/6J雄性和雌性小鼠中,我们研究了富氢水(HRW)预防性治疗对以下方面的影响:(i)触觉和冷觉异常性疼痛,(ii)握力下降和体重减轻,(iii)焦虑抑郁样行为,以及(iv)顺铂在背根神经节(DRG)和前额叶皮质(PFC)引发的炎症和氧化反应。结果表明,顺铂引发的机械性异常性疼痛和焦虑抑郁样行为在两性中表现相似,而这种化疗药物引起的冷觉异常性疼痛、握力下降和体重减轻在雌性小鼠中更为明显。尽管如此,富氢水预防性治疗可预防两性中由顺铂引起的异常性疼痛以及功能和情绪障碍。这种治疗还抑制了两性中顺铂在背根神经节和前额叶皮质激活的炎症和氧化反应,这可能解释了富氢水在雄性和雌性小鼠中的治疗作用。总之,本研究揭示了富氢水作为一种新疗法治疗与顺铂相关的异常性疼痛以及身心损伤的可能性及其可能的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8491/10741113/117cabdf05e3/antioxidants-12-02063-g001.jpg

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