Reversal of severe methotrexate-induced intestinal damage using enteral <i>n</i>-3 fatty acids

Koppelmann, Tal; Pollak, Yulia; Bejar, Jacob; Coran, Arnold G.; Sukhotnik, Igor

doi:10.1017/s0007114512000542

Cited by 17 publications

(13 citation statements)

References 27 publications

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“…In humans, it is characterized by weight loss, generalized infection and longer hospitalization time [ 12 , 13 ]. In mice, the inflammation site depends on the mouse strain and the general effects of the disease [ 21 , 22 ]. In a previous study with BALB/c mice, gut inflammation was observed mainly in the terminal jejunum and ileum, with significant weight loss [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

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Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice

et al. 2015

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BackgroundStudies showed the positive effects of omega-3 fatty acid (n-3 FA) for the treatment of inflammatory bowel disease as it alleviated the symptoms and promoted better mucosal integrity. The objective of this study was to determine whether a diet with the addition of n-3 FA helps control the inflammation observed in 5-fluorouracil (5-FU) induced mucositis.MethodsBALB/c mice were randomly divided into four groups as follows: 1: control (CTL), fed a standard chow diet; 2: CTL + n-3 FA – n-3 FA, fed a diet with n-3; 3: mucositis (MUC), fed a standard chow diet and subjected to mucositis; and 4: MUC+ n-3 FA, fed a diet with n-3 FA and subjected to mucositis. On the 8th day, the animals of the MUC and MUC + n-3 FA groups received an intraperitoneal injection of 300 mg/kg 5-FU for mucositis induction. After 24 h or 72 h, all mice were euthanized and evaluated for intestinal permeability, bacterial translocation, intestinal histology and apoptosis.ResultsMice that received the diet with n-3 FA and a 5-FU injection showed less weight loss compared to the animals of the MUC group (p < 0.005). Decreased intestinal permeability and bacterial translocation were also observed in animals fed n-3 FA, and these mice underwent mucositis compared to the MUC group (p < 0.005). These data were associated with mucosal integrity and a reduced number of apoptotic cells in the ileum mucosa compared to the mice that received the control diet and 5-FU injection.ConclusionTogether, these results show that omega-3 fatty acid decreases the mucosal damage caused by 5-FU-induced mucositis.

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Section: Discussionmentioning

confidence: 99%

“…However, mice injected with 5-FU and fed a diet with n-3 showed decreased mucosal inflammation with maintenance of the villus and crypt length, making the MUC + n-3 mice similar to the CTL mice. It was previously described that n-3 FA consumption significantly attenuates intestinal injury [ 22 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice

et al. 2015

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“…The hLZ-milk fed pigs also had deeper crypts, which contain the multicomponent local stem cells that give rise to terminally differentiated functional cells including enterocytes [38]. Previous studies show during intestinal inflammation increased crypt depth is closely correlated with increased crypt cell proliferation and improved intestinal recovery [39].…”

Section: Discussionmentioning

confidence: 99%

Consuming Transgenic Goats' Milk Containing the Antimicrobial Protein Lysozyme Helps Resolve Diarrhea in Young Pigs

et al. 2013

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Childhood diarrhea is a significant problem in many developing countries and E. coli is a main causative agent of diarrhea in young children. Lysozyme is an antimicrobial protein highly expressed in human milk, but not ruminant milk, and is thought to help protect breastfeeding children against diarrheal diseases. We hypothesized that consumption of milk from transgenic goats which produce human lysozyme (hLZ-milk) in their milk would accelerate recovery from bacterial-induced diarrhea. Young pigs were used as a model for children and infected with enterotoxigenic E. coli. Once clinical signs of diarrhea developed, pigs were fed hLZ-milk or non-transgenic control goat milk three times a day for two days. Clinical observations and complete blood counts (CBC) were performed. Animals were euthanized and samples collected to assess differences in histology, cytokine expression and bacterial translocation into the mesenteric lymph node. Pigs consuming hLZ-milk recovered from clinical signs of infection faster than pigs consuming control milk, with significantly improved fecal consistency (p = 0.0190) and activity level (p = 0.0350). The CBC analysis showed circulating monocytes (p = 0.0413), neutrophils (p = 0.0219), and lymphocytes (p = 0.0222) returned faster to pre-infection proportions in hLZ-milk fed pigs, while control-fed pigs had significantly higher hematocrit (p = 0.027), indicating continuing dehydration. In the ileum, pigs fed hLZ-milk had significantly lower expression of pro-inflammatory cytokine IL-8 (p = 0.0271), longer intestinal villi (p<0.0001), deeper crypts (p = 0.0053), and a thinner lamina propria (p = 0.0004). These data demonstrate that consumption of hLZ-milk helped pigs recover from infection faster, making hLZ-milk an effective treatment of E. coli-induced diarrhea.

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“…Omega-3 improved neutrophil function in cancer patients receiving chemotherapy [53]. Moreover, enteral n-3 polyunsaturated fatty acids reversed mucosal intestinal damage and improved intestinal recovery following MTX-induced intestinal damage in rats which could be clinically beneficial in preventing intestinal damage and in stimulating intestinal recovery in patients with chemotherapy-induced mucositis [54].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 97%

ω-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A randomized placebo-controlled study

et al. 2016

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Reversal of severe methotrexate-induced intestinal damage using enteral n-3 fatty acids

Cited by 17 publications

References 27 publications

Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice

Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice

Consuming Transgenic Goats' Milk Containing the Antimicrobial Protein Lysozyme Helps Resolve Diarrhea in Young Pigs

ω-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A randomized placebo-controlled study

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