Rutin attenuates intestinal toxicity induced by Methotrexate linked with anti-oxidative and anti-inflammatory effects.
Rutin attenuates intestinal toxicity induced by Methotrexate linked with anti-oxidative and anti-inflammatory effects.
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DOI：
10.1186/s12906-016-1069-1
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发表时间：
2016-03-10
影响因子：
--
通讯作者：
Kaithwas G
中科院分区：
文献类型：
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作者：
Gautam R;Singh M;Gautam S;Rawat JK;Saraf SA;Kaithwas G
甲氨蝶呤（MTX）被认为是癌症化疗中的抗代谢物，与炎症和氧化应激相关的各种毒性有关。据报道，甘草具有显著的抗炎、抗氧化沿着抗溃疡特性。本研究旨在证实芦丁对甲氨蝶呤（MTX）所致动物肠道毒性的影响。6组大鼠（n = 6）用生理盐水（3 ml/kg，i. p.）给药; MTX（2.5mg/kg，i.p.）;芸香苷（50和100 mg/kg，腹腔注射）;芦丁+ MTX（50 mg/kg + 2.5 mg/kg，i. p.）;芦丁+ MTX（100 mg/kg + 2.5 mg/kg，i. p.）连续七天，并在第八天处死。对肠内容物进行了生理学（pH、总酸度、游离酸度、CMDI）、生化学（TBARS、蛋白质羰基、SOD、过氧化氢酶和GSH）和免疫调节细胞因子（IL-2、IL-4和IL-10）检查。芦丁的管理证明了显着的保护对MTX损伤的肠道病变。芦丁对实验动物的游离酸、总酸和CMDI的抑制率分别为26.20%、22.05%和1.16%，与对照组相似。MTX中毒组氧化标志物和免疫调节细胞因子水平较对照组显著升高，芦丁治疗后恢复。此外，罗格列酮对环氧合酶-1和2以及15-脂氧合酶的抑制率分别为75.63%、81.00%和80.43%.甲氨蝶呤毒性的正向调节可归因于芦丁的自由基清除和抗炎（花生四烯酸途径的双重抑制）潜力。
Methotrexate (MTX) is recognized as an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. Rutin has been reported to have significant anti-inflammatory, antioxidant along with antiulcer properties. The present study was undertaken to corroborate the effect of rutin against MTX induced intestinal toxicity in experimental animals. Six groups of rats (n = 6) were dosed with normal saline (3 ml/kg,i.p.); MTX (2.5 mg/kg,i.p.); rutin (50 and 100 mg/kg,i.p.); rutin + MTX (50 mg/kg + 2.5 mg/kg,i.p.); rutin + MTX (100 mg/kg + 2.5 mg/kg,i.p.) for seven consecutive days and sacrificed on eighth day. The intestinal contents were scrutinized physiologically (pH, total acidity, free acidity, CMDI), biochemically (TBARS, protein carbonyl, SOD, catalase and GSH) and for immunoregulatory cytokines (IL-2, IL-4 and IL-10). The administration of rutin demonstrated significant protection against intestinal lesions damaged by MTX. The treatment with rutin elicited noticeable inhibition of free acidity (26.20 %), total acidity (22.05 %) and CMDI (1.16 %) in the experimental animals similar to control. In MTX treated toxic group, the levels of oxidative markers and immunoregulatory cytokines significantly increased in comparison to control, which was subsequently restored after rutin treatment. Rutin also demonstrated 75.63, 81.00 and 80.43 % inhibition of cyclooxygenase-1 and 2, and 15-lipoxygenase respectively. The positive modulation of MTX toxicity could be attributed to the free radical scavenging and anti-inflammatory (dual inhibition of arachidonic acid pathways) potential of rutin.