Wongtawatchai Tulaporn, Agthong Sithiporn, Kaewsema Atitaya, Chentanez Vilai
Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Med Assoc Thai. 2009 Nov;92(11):1485-91.
Cisplatin is used as an anti-neoplastic agent against several cancers. Neuropathy is one of its major side effects that contributes to patients' intolerance to the standard regimen. Sex-related differences have been reported in nerve injury and neuropathies. However, there has been no study on cisplatin regarding this issue.
Compare various abnormalities in cisplatin neuropathy between sexes.
Two mg/kg of cisplatin was administered intraperitoneally twice a week for five consecutive weeks. Body weight, heat latency of hind paw and sciatic motor nerve conduction velocity (MNCV), pathological alterations in the sciatic nerve and dorsal root ganglion (DRG) including the level of NGF in the sciatic nerve were examined. Untreated rats of both sexes were used as controls.
Weight loss, prolonged heat latency, and slow MNCV in the treated rats of both sexes with higher severity in males were showed. Furthermore, reduction in myelinated fiber diameter, myelin thickness, and myelinated fiber density was more severe in females, whereas, atrophy of neuronal cell body, nucleus, and nucleolus was more striking in males. The decreased level of NGF was similar between sexes.
These data suggest the differences in various aspects of cisplatin neurotoxicity between sexes. However, future studies are needed to verify this issue in a clinical condition and clarify the underlying mechanisms.
顺铂用作治疗多种癌症的抗肿瘤药物。神经病变是其主要副作用之一，会导致患者对标准治疗方案不耐受。神经损伤和神经病变存在性别差异的报道。然而，关于顺铂在这方面尚无研究。
比较两性顺铂神经病变中的各种异常情况。
每周两次腹腔注射2mg/kg顺铂，连续注射五周。检测体重、后爪热潜伏期和坐骨神经运动神经传导速度（MNCV），以及坐骨神经和背根神经节（DRG）的病理改变，包括坐骨神经中神经生长因子（NGF）的水平。未治疗的两性大鼠用作对照。
经治疗的两性大鼠均出现体重减轻、热潜伏期延长和MNCV减慢，雄性大鼠的严重程度更高。此外，有髓纤维直径、髓鞘厚度和有髓纤维密度的降低在雌性大鼠中更为严重，而神经元细胞体、细胞核和核仁的萎缩在雄性大鼠中更为明显。两性之间NGF水平的降低相似。
这些数据表明两性在顺铂神经毒性的各个方面存在差异。然而，需要进一步的研究在临床条件下验证这一问题并阐明潜在机制。
