Changes In Absorptive Function Of Rat Intestine Injured By Methotrexate

Naruhashi, Kazumasa; Nadai, Masayuki; Nakao, Makoto; Suzuki, Norihiro; Nabeshima, Toshitaka; Hasegawa, Takaaki

doi:10.1046/j.1440-1681.2000.03380.x

Cited by 26 publications

(21 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24 MTX has been shown to induce shortening or fusion of villi, and both atrophy and desquamation of the surface epithelium in various studies. [26][27][28] In the present study, the tissue sections of the rats showed normal intestinal structures in the salinetreated group. The barrier of intestinal mucosa integrity was changed and villus atrophy was remarkable in rats treated with MTX.…”

Section: Discussionsupporting

confidence: 57%

The Effectiveness of Grape Extract in Rats with Methotrexate Induced Intestinal Mucositis

Yılmaz¹,

Dağlıoğlu²,

Bayram³

et al. 2012

Turkiye Klinikleri J Med Sci

View full text Add to dashboard Cite

A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : To investigate histopathologically whether grape extract (Vitis Vinifera L), a potent free radical scavenger and can ameliorate the methotrexate -induced intestinal mucositis. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Wistar albino male rats were assigned to 3 groups: Group 1 (n=7) control group: An equal volume of distilled water that used for grape extract was given throughout the 15 days and physiological saline was administered intraperitoneally on the 10th day. Group 2 (n=10) methotrexate group: Rats received an equal volume of distilled water. A single dose of 20 mg/kg methotrexate was given intraperitoneally on the 10th day. Group 3 (n=10) methotrexate-grape extract group: The same dose of methotrexate was applied intraperitoneally on the 10 th day. For milliliters grape extract solution was administered for 15 consecutive days. Complete blood counts were analyzed from each rat. R Re es su ul lt ts s: : The control group showed normal intestinal structure. Group 2 had villus shortening and fusion with variable degrees of epithelial atrophy (p=0.001). The number of crypt cells was decreased and crypt loss was prominent (p=0.007). Inflammatory infiltration and decreased goblet cell number in both villi and crypts were distinctive (p<0.001). Villous and crypt injury, and inflammatory infiltration was less in group 3. In addition, goblet cells were increased. The difference was significant between group 2 and 3 for the jejunum damage (p=0.021). Hemoglobin levels increased in group 3. C Co on nc cl lu us si io on n: : Present study suggested that grape extract could be useful in the ameliorating intestinal damage caused by methotrexate. Its effect could be attributed to its antioxidant properties. Grape extract may have a clinical application in cancer chemotherapy.K Ke ey y W Wo or rd ds s: : Methotrexate; mucositis; grape seed extract; intestinal diseases Ö ÖZ ZE ET T A Am ma aç ç: : Potansiyel bir serbest radikal yok edici olan üzüm ekstresinin (Vitis Vinifera L) metotreksat ile oluşturulmuş ince bağırsak mukozitini histopatolojik olarak iyileştirip iyileştirmediğini araştırmak. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Wistar albino erkek sıçanlar 3 gruba ayrıldı. Grup 1 (n=7) kontrol grup: Üzüm ekstresi ile aynı miktarda olan distile su 15 gün boyunca kullanıldı ve 10. günde serum fizyolojik intraperitoneal olarak verildi. Grup 2 (n=10) metotreksat grubu: Sıçanlar aynı miktar distile su aldılar. Tek doz 20 mg/kg metotreksat 10. günde verildi. Grup 3 (n=10) Metotreksatüzüm ekstresi grubu: Aynı doz metotreksat 10. günde intraperitoneal olarak uygulandı. Dört mililitre üzüm ekstresi solüsyonu 15 gün boyunca alındı. Tam kan sayımı her bir sıçandan analiz edildi. B Bu ul lg gu ul la ar r: : Kontrol grup normal ince bağırsak yapısını gösterdi. Grup 2 değişik derecelerde epitel atrofisi ile birlikte villüs kısalması ve füzyonuna sahipti (p=0.001). Kript hücrelerinin sayısı azalmış ve kript kaybı belirgindi (p=0.007). Hem villüs...

show abstract

Section: Discussionsupporting

confidence: 57%

The Effectiveness of Grape Extract in Rats with Methotrexate Induced Intestinal Mucositis

Yılmaz¹,

Dağlıoğlu²,

Bayram³

et al. 2012

Turkiye Klinikleri J Med Sci

View full text Add to dashboard Cite

show abstract

“…In this study, the general characteristics (villus atrophy, crypt loss, goblet cell depletion) of MTX-induced small intestinal mucositis were the same as described in previous studies [4,19,20]. Proliferation of small intestinal epithelial cells occurs in the crypts.…”

Section: Discussionmentioning

confidence: 62%

“…Methotrexate (MTX) is an anticancer drug that has been shown to be highly effective against various malignancies [1]. The antimitotic effect of MTX is known to give rise to the malabsorption syndrome [2][3][4] that decreases the surface area for absorption caused by histological alterations such as shortened microvilli, resulting in less absorption of nutrients [5]. In addition, MTX depresses absorption of certain drugs from the small intestine [5], metabolic activity and active transport capacity of the intestinal mucosa [6].…”

Section: Introductionmentioning

confidence: 99%

Effect of Vitamin A against Methotrexate-Induced Damage to the Small Intestine in Rats

Yüncü¹,

Eralp²,

Koruk

et al. 2004

Med Princ Pract

View full text Add to dashboard Cite

Objective: The aim of the present study was to examine whether or not the administration of vitamin A (VA) protects against methotrexate (MTX)-induced damage to small intestinal epithelium. Materials and Methods: Sixty-three male Wistar albino rats, 10–12 weeks old, weighing 240–280 g, were divided into three groups: (1) controls, (2) rats receiving MTX treatment alone, and (3) rats receiving MTX plus VA treatment. A single dose of MTX (20 mg/kg MTX in 20 ml vehicle) was administered to the rats intraperitoneally. For MTX plus VA treated groups, retinol palmitate (VA) 5,000 IU/kg dissolved in 0.5 ml sunflower oil was administered by intragastric tube 3 days prior to MTX treatment and continued till the rats were sacrificed. The control group was treated with vehicle. Both control and MTX-alone groups were also treated with sunflower oil as a placebo. The rats were sacrificed on the 2nd, 4th and 6th day after MTX treatment. Tissue samples from the jejunum were taken for histopathological analysis. Results: MTX treatment induced villus shortening and fusion, epithelial atrophy, crypt loss, inflammatory infiltrate in the lamina propria, and goblet cell depletion. The pre- and post-treatment administration of VA decreased the severity of jejunal damage caused by MTX treatment. Conclusion: Our results confirmed that administration of VA decreased the MTX-induced damage to the small intestine. This protective effect of VA may have clinical applications in cancer chemotherapy.

show abstract

“…Mucositis is characterized by major morphologic changes of the intestinal epithelium, such as epithelial flattening, villus atrophy, and specific down-regulation of the enterocytespecific gene expression that is crucial for degradation and absorption of nutrients (3)(4)(5). It is unknown how this condition effects digestion and absorption of enteral nutrition.…”

mentioning

confidence: 99%

Chemotherapy Does Not Influence Intestinal Amino Acid Uptake in Children

et al. 2007

View full text Add to dashboard Cite

Chemotherapy will frequently induce intestinal damage (mucositis). Enteral nutrition is then often withheld for fear of impaired intestinal absorption as shown in animal models. There is no clinical evidence, however, that absorption is indeed compromised during chemotherapy-induced mucositis. The aim of this study was to evaluate systemic availability of dietary amino acids (leucine) during chemotherapy-induced mucositis. We studied eight childhood cancer patients (age 1.5-16 y) on 2 d, i.e. the day before chemotherapy and 3-5 d after. Chemotherapy-induced oral mucositis and diarrhea were scored on a World Health Organization toxicity scale. Stable isotope tracers were used to measure first-pass splanchnic leucine uptake and whole-body leucine kinetics. Patients showed increased mucositis and/or diarrhea toxicity scores (p Ͻ 0.0001) after chemotherapy. Systemic availability of enterally administered leucine was not significantly affected by chemotherapy (before 60%, after 90%, p ϭ 0.46). Interestingly, five patients already showed a negative leucine balance before chemotherapy. In conclusion, most children receiving chemotherapy are already catabolic before start of a new cycle of chemotherapy. Amino acid transport as measured by leucine uptake in the intestine is not affected by chemotherapyinduced mucositis. C hemotherapy may severely damage the intestinal mucosa, resulting in a condition referred to as mucositis (1,2). Mucositis is characterized by major morphologic changes of the intestinal epithelium, such as epithelial flattening, villus atrophy, and specific down-regulation of the enterocytespecific gene expression that is crucial for degradation and absorption of nutrients (3-5). It is unknown how this condition effects digestion and absorption of enteral nutrition.Normally, the intestine itself metabolizes a substantial part of the nutrients absorbed from the intestinal lumen in first-pass splanchnic uptake (6,7). Animal and human studies have shown that 20 -80% of dietary essential amino acids are used within the intestine (8 -10). The more nutrients are used by the small intestine, the fewer essential amino acids are systemically available for whole-body energy metabolism and protein synthesis. It is unknown whether chemotherapy-induced mucositis affects first-pass splanchnic amino acid uptake. We hypothesized, first, that chemotherapy-induced mucositis will lead to lower nutrient uptake by the intestine and, second, that it will lead to a higher intestinal utilization rate due to mucosal regeneration. The combined result would be a lower systemic availability of dietary amino acids.To test these hypotheses we determined first-pass splanchnic uptake of dietary leucine, an essential amino acid, in pediatric patients before and after receiving mucotoxic chemotherapy. METHODS Subjects.The ethics review board of the Erasmus MC-Sophia Children's Hospital approved the study. Informed consent was obtained from parents and patients, as appropriate. Eligible subjects were patients aged between 1 and...

show abstract

Changes In Absorptive Function Of Rat Intestine Injured By Methotrexate

Cited by 26 publications

References 24 publications

The Effectiveness of Grape Extract in Rats with Methotrexate Induced Intestinal Mucositis

The Effectiveness of Grape Extract in Rats with Methotrexate Induced Intestinal Mucositis

Effect of Vitamin A against Methotrexate-Induced Damage to the Small Intestine in Rats

Chemotherapy Does Not Influence Intestinal Amino Acid Uptake in Children

Contact Info

Product

Resources

About