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

Lin²,

et al. 2013

PLoS ONE

PurposeHigh-dose chemotherapy using methotrexate (MTX) frequently induces side effects such as mucositis that leads to intestinal damage and diarrhea. Several natural compounds have been demonstrated of their effectiveness in protecting intestinal epithelial cells from these adverse effects. In this paper, we investigated the protection mechanism of lutein against MTX-induced damage in IEC-6 cells originating from the rat jejunum crypt.MethodsThe cell viability, induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential in IEC-6 cells under MTX treatment were examined in the presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR.ResultsThe cell viability of IEC-6 cells exposed to MTX was decreased in a dose- and time-dependent manner. MTX induces mitochondrial membrane potential loss, ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre-treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The expression of SOD was up-regulated by the pre-treatment of lutein in the MTX-treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells from the chemo-drugs induced damage through increasing ROS scavenging ability.ConclusionThe MTX-induced apoptosis of IEC-6 cells was shown to be repressed by the pre-treatment of lutein, which may represent a promising adjunct to conventional chemotherapy for preventing intestinal damages.

Section: Introductionmentioning

confidence: 99%

Lutein Protects against Methotrexate-Induced and Reactive Oxygen Species-Mediated Apoptotic Cell Injury of IEC-6 Cells

Lin²,

et al. 2013

PLoS ONE

“…Intestinal damage induced by the administration of antitumor drugs such as MTX is attributed to damage to the crypt cells (Taminiau et al, 1980;Yüncü et al, 2004). The present study suggests that the damage induced by MTX in the small intestine is reduced by AGE.…”

Section: Resultsmentioning

confidence: 48%

“…There are several published reports showing the use of MTX together with lecovorin, vitamin A, vitamin E, soy flour and garlic extracts. Application of vitamin A, for example, has been demonstrated to protect the small intestines from damage (Tsurui et al, 1990;Yüncü et al, 2004). Kosakai et al (1991) suggested that vitamin A may influence the crypt cells by activating protein synthesis.…”

mentioning

confidence: 99%

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

Yüncü

Eralp

Çelik

2006

Phytotherapy Research

Self Cite

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.

Turkiye Klinikleri J Med Sci

“…36 A similar result was proven by Yüncü et al in an experimental study performed with the supplementation of vitamin A which had antioxidant properties. 37 In our animal model, the attenuating of villi damaged was noteworthy in the intestinal mucosa after the use of GE. Furthermore, increased crypt proliferation was noticeable in our study.…”

mentioning

confidence: 63%

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

Yılmaz¹,

Dağlıoğlu²,

Bayram³

et al. 2012

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...