Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract

Pinheiro, F.V.; Pimentel, Victor Câmera; Bona, Karine Santos De; Scola, Gustavo; Salvador, Mirian; Funchal, Cláudia; Moretto, Maria Beatriz

doi:10.1002/cbf.1627

Cited by 29 publications

(25 citation statements)

References 30 publications

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“…As may be observed in this study, MTX caused liver and kidney injuries by oxidative damage. Although the mechanism of MTX-induced hepatorenal toxicity is not well understood, recent studies indicated the oxidative damage to be the causative factor (19). It had been shown that the cytosolic NADP-dependent dehydrogenases and NADPmalic enzymes were inhibited by MTX, suggesting that the drug could either decrease the availability of reduced NADPH in cells (12) or NADPH was used by GSH reductase to reduce an important cytosolic antioxidant, GSH.…”

Section: Discussionmentioning

confidence: 99%

“…The significant reduction in GSH levels promoted by MTX could cause two results: first, in conjunction with reduced GSH levels, inactivation of reactive molecules; second, the tendency of covalent bonding with other macromolecules increases. This could lead to a reduction in effectiveness of the antioxidant enzyme defense system, sensitizing the cells to ROS (19). Tissue CAT is an important oxidant detoxifier, playing a key role in the elimination of lipid peroxides and H 2 O 2.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats

et al. 2017

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Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats

et al. 2017

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“…These molecules possess a structure that confers on them an antioxidant property, which has been demonstrated to exert a novel spectrum of biological, pharmacological, therapeutic, and chemoprotective effects against oxygen free radicals and oxidative stress, which can be used as herbal remedies especially for controlling oxidative damages (El-Ashmawy et al, 2007and Dulundu et al, 2007. Several studies have indicated that extracts obtained from grape seed inhibit enzyme systems that are responsible for the production of free radicals, and that they are antimutagenic and anticarcinogenic (Pinheiro et al, 2010). For this reason, grape seed extract is widely consumed as a dietary supplement in addition to the chemotherapeutic agents in cancer treatment (cetin et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Inhibitory Effects of Grape Seeds Powder, Extract and Oil on Gentamicin Induced Nephrotoxicity in Rats

Nagib

2014

Egyptian Journal of Nutrition and Health

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This study was designed to determine the Inhibitory effect of grape seeds powder, extract and oil on gentamicin-induced nephrotoxicity in rats.The study was carried out on 30 adult albino male rats Sprague-Dawley strain were classified into two groups: The first group (n= 6) left as normal control group(-ve), fed on basal diet, the second group(n= 24) injected with gentamicin (100 mg/kg/day for 7 days i.p). These animals were divided into 4 groups 6 rats each of these , control (+ve) group and 3 groups were treated with grape seeds powder ( 10 % of diet ) , grape seeds extract (300mg/kg b.w.orally by stomach tube) and grape seeds oil (4 ml/kg b.w. orally by stomach tube) respectively.The treatment period was designed for eight weeks. The results revealed that, Gentamicin injection induced marked nephrotoxicity as evidenced by significant elevation in serum levels of creatinine, urea, uric acid, A/G ratio, MDA ,renin hormone, phosphorus and potassium, with significant reduction in serum levels of total protein, albumin, globulin, (SOD), (GPX), (GST) ,catalase antioxidant enzymes, erythropoietin hormone (EPO) , vitamin D and Ca . While the rat groups treated with grape seeds powder ,extract and oil showed significant improvement of the levels of serum total protein, albumin, globulin, kidney tissue superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione transferase (GST) , catalase antioxidant enzymes, erythropoietin hormone (EPO) and vitamin D, and significant decrease in serum creatinine, urea, uric acid, albumin/globulin ratio ,kidney tissue malondialdehyde (MDA), renin hormone, phosphorus and potassium compared with control(+ve) group. In conclusion, feeding rats with grape seeds powder ,extract and oil may significantly reduce nephrotoxicity, So this study recommend the use of grape seeds especially grape seeds oil or grape seeds extract for humans suffering nephrotoxicity, could be of value.

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“…[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. In the present study, the dilution of the concentrated GE which included skin, seed and juice was tried after inducing intestinal damage with MTX.…”

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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Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract

Cited by 29 publications

References 30 publications

Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats

Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats

Inhibitory Effects of Grape Seeds Powder, Extract and Oil on Gentamicin Induced Nephrotoxicity in Rats

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

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