Rutin ameliorates methotrexate induced hepatic injury in rats

Erdoğan, Esra; Ilgaz, Yasin; Gürgör, Pınar Naile; Öztaş, Yeşim; Topal, Turgut; Öztaş, Emin

doi:10.1590/s0102-865020150110000009

Cited by 52 publications

(41 citation statements)

References 22 publications

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“…RUT, like many flavonoids, has demonstrated antioxidant properties [52], in addition to the ability to relieve oxidative stress in biological systems. We observed that RUT exhibited antioxidant effects against intestinal mucositis, increasing GSH levels and decreasing MDA levels in mice presenting 5-FU-induced intestinal mucositis; this was consistent with the findings of previous studies that demonstrated that RUT exerts antioxidant effects by decreasing MDA levels [53,54] and increasing GSH and superoxide dismutase levels [55][56][57].…”

Section: Discussionsupporting

confidence: 92%

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

et al. 2020

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Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.

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Section: Discussionsupporting

confidence: 92%

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

et al. 2020

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“…Furthermore, rutin always provided significant improvement regarding liver injury in the results, which suggested that it can be regarded as the functional compound of red quinoa bran. In the previous study, rutin also has been proven the protective effect on methotrexate-induced liver injury in rats [19].…”

Section: Discussionmentioning

confidence: 99%

Red Quinoa Bran Extracts Protects against Carbon Tetrachloride-Induced Liver Injury and Fibrosis in Mice via Activation of Antioxidative Enzyme Systems and Blocking TGF-β1 Pathway

Lin

Cheng

et al. 2019

Nutrients

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The late stages of liver fibrosis are considered to be irreversible. Red quinoa (Chenopodium formosanum Koidz), a traditional food for Taiwanese aborigines, was gradually developed as a novel supplemental food due to high dietary fibre and polyphenolic compounds. Its bran was usually regarded as the agricultural waste, but it contained a high concentration of rutin known as an antioxidant and anti-inflammatory agent. This study is to explore the effect of red quinoa bran extracts on the prevention of carbon tetrachloride (CCl4)-induced liver fibrosis. BALB/c mice were intraperitoneally injected CCl4 to induce liver fibrosis and treated with red quinoa whole seed powder, bran ethanol extracts, bran water extracts, and rutin. In the results, red quinoa powder provided more protection than rutin against CCl4-induced oxidative stress, pro-inflammatory factor expression and fibrosis development. However, the bran ethanol extract with high rutin content provided the most liver protection and anti-fibrosis effect via blocking the tumor necrosis factor alpha (TNF-α)/interleukin 6 (IL-6) pathway and transforming growth factor beta 1 (TGF-β1) pathway.

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“…Rubin (2001) postulated that severe degeneration of cell organelles especially the mitochondria and the rough endoplasmic reticulum, could be attributed to the oxygen metabolites with deficiency of the protective enzymes from the liver following drug treatments. Erdogan et al (2015) suggested that Mtx increased MDA levels which confirmed the oxidative stress and explained the tissue damage.…”

Section: Discussionmentioning

confidence: 85%

“…The mechanisms of Mtx toxicity are not yet fully understood, but recent studies have shown that a decrease in the levels of cellular glutathione (GSH) and oxygen radicals are linked with the development of Mtx-induced toxicity ( Johovic et al, 2003 ;Cetinkaya et al, 2006;Sener et al, 2006 ;Cetin et al, 2008;Erdogan et al, 2015).It was demonstrated that cytosolic nicotinamide adenosine diphosphate (NADP)-dependent dehydrogenases are inhibited by Mtx, suggesting that the drug decreases the availability of NADPH in cells. Under normal conditions, NADPH is used by glutathione reductase to maintain the reduced state of GSH, an important cytosolic antioxidant that protects cells against reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

Hepatotoxicity of Methotrexate and the Possible Ameliorative Effect of L-Carnitine: Ultrastructural Study

Kadry

Ashry

Abuzeid

et al. 2016

Journal of Scientific Research in Science

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Methotrexate (Mtx) is widely used in various cancer and inflammatory diseases. Hepatotoxicity is the most serious side effect in long-term Mtx treatment. Therefore, the present study aimed to investigate the protective effect of L-Carnitine against Mtx-induced injury in rat's hepatocytes. Fifty male albino rats, each weighing 120-130g were used. The experimental animals were equally divided into five groups , 10 rats each, and treated intraperitoneally (twice /week) as follows : (1) rats did not receive any treatment (control group ); (2) rats given 300mg L-Carnitine /100g b.w. for 4 weeks ; (3) rats given 0.045mg Mtx /100g b.w. for 4 weeks ; (4) rats given 0.045mg Mtx /100g b.w. with 300mg L-Carnitine /100g b.w. for 4 weeks ; (5) rats given 0.045mg Mtx /100g b.w. for 4 weeks then given 300mg L-Carnitine /100g b.w. for other 4 weeks.In Methotrexate-treated group, the ultrastructural study on hepatocytes revealed pyknotic nuclei with abnormally electron-dense chromatin, irregular nuclear envelopes, electron-dense mitochondria and fragmented rough endoplasmic reticulum.In addition to dilatation and congestion of the hepatic sinusoids as well as increase in lipid droplets and collagen fibers. Rats co-treated with L-Carnitine against Mtx showed significant improvement in the ultrastructure abnormalities of hepatocytes caused by Mtx. On the other hand, mild to moderate improvement in hepatocytes were observed in the group treated with Mtx followed by L-Carnitine. These results indicated that co-and post L-Carnitine treatment can diminish Mtx-induced liver ultrastructural injuries. The beneficial effect was more pronounced in L-Carnitine co treated with Methotrexate.

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Rutin ameliorates methotrexate induced hepatic injury in rats

Abstract: Rutin may be a potential adjuvant drug to reduce the hepatic side effects observed during Mtx therapy for various clinical conditions.

Cited by 52 publications

References 22 publications

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

Red Quinoa Bran Extracts Protects against Carbon Tetrachloride-Induced Liver Injury and Fibrosis in Mice via Activation of Antioxidative Enzyme Systems and Blocking TGF-β1 Pathway

Hepatotoxicity of Methotrexate and the Possible Ameliorative Effect of L-Carnitine: Ultrastructural Study

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