Abstract
BackgroundA common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin.MethodsWe conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models.ResultsA total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group.ConclusionsGreen tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.
Highlights
A common side effect of oxaliplatin is peripheral neurotoxicity
Behavioral studies Assessment of sensory threshold values in hind paws The sensory threshold test in the right hind paw was conducted before oxaliplatin administration and at weeks 2, 4, and 6 after oxaliplatin administration
Before oxaliplatin administration and at week 2 after oxaliplatin administration, there was no significant difference in sensory thresholds between the two groups (P = 1.0 and P = 0.39, respectively)
Summary
A common side effect of oxaliplatin is peripheral neurotoxicity. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin. Neurotoxicity is a common adverse effect associated with antineoplastic agents Of these agents, oxaliplatin has been commonly used in clinical practice to treat various cancers of the gastrointestinal tract. A common and dose-limiting side effect of oxaliplatin is peripheral neurotoxicity (PN), which is known to be cumulative [1]. Oxaliplatin treatment induces an acute neurotoxicity, characterized by a rapid onset of cold-induced distal dysesthesia and a chronic sensory peripheral neuropathy [1]. The chronic, sensory, oxaliplatin-induced PN may be induced by decreased cellular metabolism and axoplasmatic transport secondary to the accumulation of platinum compounds in dorsal root ganglia (DRG) cells [5], by the impairment of cellular mitochondrial oxygen consumption [6], or by the prolonged activation of voltage-gated Na+ channels, which induce cellular stress in sensory nerve cells via excess Ca2+ influx [7]
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