Omega-3 fatty acids are able to modulate the painful symptoms associated to cyclophosphamide-induced-hemorrhagic cystitis in mice
Omega-3 fatty acids are able to modulate the painful symptoms associated to cyclophosphamide-induced-hemorrhagic cystitis in mice
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DOI：
10.1016/j.jnutbio.2015.09.007
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发表时间：
2016-01-01
影响因子：
5.6
通讯作者：
Campos, Maria M.
中科院分区：
文献类型：
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作者：
Freitas, Raquel D. S.;Costa, Kesiane M.;Campos, Maria M.
本研究探讨了长期膳食鱼油补充剂或ω-3脂肪酸二十二碳六烯酸（DHA）急性给药对抗癌药物环磷酰胺（CTX）诱导的小鼠出血性膀胱炎（HC）的影响。通过单次腹腔注射（300 mg/kg ip）在小鼠中诱导MC。在21天内，动物接受了四种不同的饮食，分别含有10%和20%的玉米或鱼油。单独的组接受DHA通过ip（1 μ mol/kg）或鞘内（i.t; 10 μ g/部位）途径，1小时或15分钟前，给药。在注射后1 h至6 h进行行为学测试（自发伤害感受和机械异常性疼痛）。在安乐死后（6 h）评价膀胱炎性变化、血细胞计数和血清细胞因子。进行免疫组织化学分析以评估脊髓星形胶质细胞和小胶质细胞活化或GPR 40/FFAR 1表达。无论是鱼油补充剂或DHA治疗（ip和i.t）显着预防内脏痛，而不影响CYP诱发的膀胱炎性变化。此外，全身DHA显着防止嗜中性粒细胞/淋巴细胞减少症引起的肥胖，而这种脂肪酸没有显着影响血清细胞因子。DHA还调节脊髓星形胶质细胞活化和GPR 40/FFAR 1表达。补充富含omega-3脂肪酸或肠道外DHA的鱼油可能是接受化疗方案的癌症患者的有趣营养方法。(C)2015 Elsevier Inc. All rights reserved.
This study investigated the effects of the long-term dietary fish oil supplementation or the acute administration of the omega-3 fatty acid docosahexaenoic acid (DHA) in the mouse hemorrhagic cystitis (HC) induced by the anticancer drug cyclophosphamide (CYP). MC was induced in mice by a single CYP injection (300 mg/kg ip). Animals received four different diets containing 10% and 20% of corn or fish oil, during 21 days. Separated groups received DHA by ip (1 mu mol/kg) or intrathecal (i.t; 10 mu g/site) routes, 1 h or 15 min before CYP. The behavioral tests (spontaneous nociception and mechanical allodynia) were carried out from 1 h to 6 h following CYP injection. Bladder inflammatory changes, blood cell counts and serum cytokines were evaluated after euthanasia (at 6 h). Immunohistochemistry analysis was performed for assessing spinal astrocyte and microglia activation or GPR40/FFAR1 expression. Either fish oil supplementation or DHA treatment (ip and i.t) markedly prevented visceral pain, without affecting CYP-evoked bladder inflammatory changes. Moreover, systemic DHA significantly prevented the neutrophilia/lymphopenia caused by CYP, whereas this fatty acid did not significantly affect serum cytokines. DHA also modulated the spinal astrocyte activation and the GPR40/FFAR1 expression. The supplementation with fish oil enriched in omega-3 fatty acids or parenteral DHA might be interesting nutritional approaches for cancer patients under chemotherapy schemes with CYP. (C) 2015 Elsevier Inc. All rights reserved.