Vol. 8, Issue 12 (2019)

Author(s):
MM Ostrovskyi

Abstract:
Chemotherapy-induced peripheral neuropathy is a common and potentially severe side effect of cancer drugs that target microtubules. This has important clinical significance because such neuropathy is the most frequent cause of dose reduction or treatment discontinuation in patients treated for cancer with commonly used antimitotic drugs including paclitaxel. At this day, there are no proven effective chemicals for the prevention or treatment of paclitaxel-induced peripheral neuropathy or chemotherapy-induced peripheral neuropathy in general. 2-ethyl-6-methyl-3-hydroxypyridine succinate is a molecule, derivative of succinic acid with neuroprotective, membrane protective, nootropic, antihypoxic, sedative action. We investigated the pharmacological potential of 2-ethyl-6-methyl-3-hydroxypyridine succinate in preventing paclitaxel-induced peripheral neuropathy. Paclitaxel was injected intraperitoneally to random bred male-rats at a dose of 2 mg/kg 4 times every other day which resulted in mechanical allodynia and thermal hyperalgesia. 2-ethyl-6-methyl-3-hydroxypyridine succinate was administered intraperitoneally at a dose of 10 mg/kg within 10 following days after last paclitaxel injection. The signs of paclitaxel-induced peripheral neuropathy (mechanical allodynia and thermal hyperalgesia) were measured within 150 days of experiment using the von Frey filament assay and Hot Plate test, respectively. Our results indicate that 2-ethyl-6-methyl-3-hydroxypyridine succinate administration exerts a protective effect against paclitaxel-induced neuropathy by increasing of reduced mechanical withdrawal thresholds (von Frey assay) and reaction latency (Hot Plate test) on the 7th, 14th and 30th days of experiment. 2-ethyl-6-methyl-3-hydroxypyridine succinate attenuates paclitaxel-induced neuropathic pain in rodents and could be a promising therapeutic outcome for the management of this intractable disease in humans.