Ghirardi Orlando, Vertechy Mario, Vesci Loredana, Canta Annalisa, Nicolini Gabriella, Galbiati Stefania, Ciogli Cristina, Quattrini Gianni, Pisano Claudio, Cundari Sante, Rigamonti Laura Maria
Research and Development, Sigma-Tau S.p.A. Industrie Farmaceutiche Riunite, Rome, Italy.
In Vivo. 2005 May-Jun;19(3):631-7.
We tested the hypothesis that acetyl-L-carnitine (ALC) may have a protective and a curative role in chemotherapy-induced hyperalgesia in vivo, in animal models of cisplatin-, paclitaxel- and vincristine-induced neuropathy. In addition, the possible interaction between ALC and vincristine antineoplastic action was assessed.
Chemotherapy-induced peripheral neuropathy (CIPN) was induced in different groups of rats. The effect of ALC was evaluated both when its administration was started together with the administration of anticancer drugs ("preventive" protocol) and when ALC administration was started later on during treatment ("curative" protocol).
The ALC treatment significantly prevented the lowering of the mechanical nociceptive threshold when the administration started concomitantly and, respectively, with cisplatin, paclitaxel and vincristine as compared to each drug alone. Furthermore, when ALC administration was started later on during treatment, at well-established neuropathy, ALC was able to restore the mechanical nociceptive threshold within a few days. Finally, experiments indicated that ALC does not interfere with the antitumor effects of vincristine.
Considering the absence of any satisfactory treatment currently available for CIPN in a clinical setting, these are important observations, opening up the possibility of using ALC to treat a wide range of patients who have undergone chemotherapy and developed sensory peripheral neuropathy.
我们检验了以下假设:在顺铂、紫杉醇和长春新碱诱导的神经病变动物模型中,乙酰左旋肉碱(ALC)可能在体内对化疗诱导的痛觉过敏具有保护和治疗作用。此外,还评估了ALC与长春新碱抗肿瘤作用之间可能的相互作用。
在不同组大鼠中诱导化疗诱导的周围神经病变(CIPN)。当ALC与抗癌药物同时给药(“预防性”方案)以及在治疗后期开始给予ALC(“治疗性”方案)时,评估ALC的效果。
与单独使用每种药物相比,当ALC分别与顺铂、紫杉醇和长春新碱同时给药时,显著预防了机械性伤害感受阈值的降低。此外,当在治疗后期,即在已确立的神经病变时开始给予ALC,ALC能够在几天内恢复机械性伤害感受阈值。最后,实验表明ALC不干扰长春新碱的抗肿瘤作用。
考虑到目前临床上对于CIPN尚无任何令人满意的治疗方法,这些是重要的观察结果,为使用ALC治疗广泛的接受化疗并发生感觉性周围神经病变的患者开辟了可能性。