Institute for Health & Sport, Victoria University, Melbourne, VIC 3021, Australia.
Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Biomolecules. 2023 Feb 1;13(2):276. doi: 10.3390/biom13020276.
Nausea and vomiting are common gastrointestinal side effects of oxaliplatin chemotherapy used for the treatment of colorectal cancer. However, the mechanism underlying oxaliplatin-induced nausea and vomiting is unknown. The stomach is involved in the emetic reflex but no study investigated the effects of oxaliplatin treatment on the stomach. In this study, the in vivo effects of oxaliplatin treatment on eating behaviour, stomach content, intrinsic gastric neuronal population, extrinsic innervation to the stomach, levels of mucosal serotonin (5-hydroxytryptamine, 5-HT), and parasympathetic vagal efferent nerve activity were analysed. Chronic systemic oxaliplatin treatment in mice resulted in pica, indicated by increased kaolin consumption and a reduction in body weight. Oxaliplatin treatment significantly increased the stomach weight and content. The total number of myenteric and nitric oxide synthase-immunoreactive neurons as well as the density of sympathetic, parasympathetic, and sensory fibres in the stomach were decreased significantly with oxaliplatin treatment. Oxaliplatin treatment significantly increased the levels in mucosal 5-HT and the number of enterochromaffin-like cells. Chronic oxaliplatin treatment also caused a significant increase in the vagal efferent nerve activity. The findings of this study indicate that oxaliplatin exposure has adverse effects on multiple components of gastric innervation, which could be responsible for pica and gastric dysmotility.
恶心和呕吐是结直肠癌化疗中常用的奥沙利铂引起的常见胃肠道副作用。然而，奥沙利铂引起恶心和呕吐的机制尚不清楚。胃参与呕吐反射，但没有研究调查奥沙利铂治疗对胃的影响。在这项研究中，分析了奥沙利铂治疗对进食行为、胃内容物、固有胃神经元群、胃外神经支配、黏膜 5-羟色胺（5-HT）水平和副交感迷走神经传出神经活动的体内影响。慢性系统奥沙利铂治疗在小鼠中导致了嗜食癖，表现为高岭土消耗增加和体重减轻。奥沙利铂治疗显著增加了胃的重量和内容物。奥沙利铂治疗后，胃的肌间和一氧化氮合酶免疫反应神经元总数以及胃中的交感、副交感和感觉纤维密度显著降低。奥沙利铂治疗显著增加了黏膜 5-HT 水平和肠嗜铬样细胞的数量。慢性奥沙利铂治疗还导致迷走神经传出神经活动的显著增加。这项研究的结果表明，奥沙利铂暴露对胃神经支配的多个成分有不良影响，这可能是导致嗜食癖和胃动力障碍的原因。
