Methotrexate enterotoxicity: Influence of drug dose and timing in the rat

Pinkerton, CR; Milla, Peter J.

doi:10.1038/bjc.1984.15

Cited by 28 publications

(12 citation statements)

References 14 publications

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“…However, the steps in the pathway of VA-stimulated biosynthesis need to be elucidated for proper interpretation of this protective effect of VA on a molecular level. Furthermore, MTX-induced malabsorption may not be simply a consequence of reduced villus surface area but may also be involved in the interaction of cell toxicity and alteration in villus population dynamics [31]. Since VA contributes to membrane stabilization [30], the protective action of VA may also be related to this epithelial cell membrane-stabilizing effect.…”

Section: Discussionmentioning

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

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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.

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Section: Discussionmentioning

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

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“…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: Discussionmentioning

confidence: 77%

“…In order to minimize side-effects of MTX in patients, the studies focused on antioxidants. [28][29][30][31] One of them, GE, was mostly emphasized on its antioxidant properties in a number of in vitro and in vivo studies. 17,32,33 Various studies also presented that GE has been tried in the repair of MTX-induced intestinal injury.…”

Section: Discussionmentioning

confidence: 99%

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

Yılmaz¹,

Dağlıoğlu²,

Bayram³

et al. 2012

Turkiye Klinikleri J Med Sci

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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...

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“…MTX, similar to other chemotherapeutic agents and radiation treatment, increases the incidence of apoptosis in the areas of rapidly dividing cells, including gastrointestinal tract mucosa (Barry et al, 1990). On the other hand, MTX-induced malabsorption may not be simply a consequence of reduced villus surface area but may involve the interaction of cell toxicity and alteration in villus population dynamics (Pinkerton and Milla, 1984). In doing so, the protective action of AGE may also be related to a cytoprotective effect for the small intestine.…”

Section: Biochemical Resultsmentioning

confidence: 98%

Effect of aged garlic extract against methotrexate‐induced damage to the small intestine in rats

Yüncü

Eralp

Çelik

2006

Phytotherapy Research

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Methotrexate (MTX) chemotherapy is often accompanied by side effects such as gastrointestinal ulceration and diarrhea. The aim of this study was to examine histologically whether an aged garlic extract (AGE) had a protective effect on the small intestine of rats with MTX-induced damage. Forty male Wistar albino rats were randomized into experimental and control groups and divided into four groups of ten animals. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, AGE (250 mg/kg) was administered orally every day at the same time by intragastric intubation until the rats were killed. To the third group, AGE only was given. The fourth group was the control. All animals were killed 4 days after the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA levels. Before killing, intracardiac blood was obtained from each animal to perform biochemical analysis (plasma lactate level). MTX was found to lead to damage in the jejunal tissues and to increase the MDA and lactate levels in the plasma. Administration of the AGE decreased the severity of jejunal damage, but increased MDA and lactate levels caused by MTX treatment on the other hand. These results suggest that AGE may protect the small intestine of rats from MTX-induced damage. Thus this study substantiated the thought that the protective effect of AGE is derived from the manner in which it interacts with crypt cells.

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Methotrexate enterotoxicity: Influence of drug dose and timing in the rat

Cited by 28 publications

References 14 publications

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

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

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

Effect of aged garlic extract against methotrexate‐induced damage to the small intestine in rats

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