Effect of Rutin on Cisplatin-induced Small Intestine (Jejunum) Damage in Rats

Bilg, Asli Ozbek; Topal, İsmail; Akbul, Ulas Emre; Cimen, Orhan; Kolkiran, Abdulkerim; Akturan, Selçuk; Cim, Ferda Keskin; Çankaya, Murat; Eden, Arif Onur; Süleyman, Zeynep

doi:10.3923/ijp.2018.1136.1144

Cited by 4 publications

(1 citation statement)

References 27 publications

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“…Furthermore, RUT prevented histopathological alterations at the 200 mg/kg dose. The protective abilities of RUT in the gastrointestinal tract have been reported in the literature [42,43] at doses similar to those used in the present study, corroborating the results obtained.…”

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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Effect of rutin on experimentally induced small intestinal ischemia reperfusion injury in rats: A biochemical and histopathological evaluation

Çimen¹,

Cimen²,

Altuner³

et al. 2021

Journal of Surgery and Medicine

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Background/Aim: The large amount of oxygen presented to the ischemic tissue in reperfusion causes the formation of excess free oxygen radicals and results in oxidative damage. Rutin is a flavonoid with potent antioxidant and anti-inflammatory effects. The aim of this study is to examine the effect of rutin on I/Rinduced small intestinal (ileum) oxidative damage in rats. Methods: The animals were divided into three groups as follows: Intestinal ischemia-reperfusion (IIR), 50 mg/kg rutin+intestinal ischemia reperfusion (RIIR) and sham operation (Sham). Rutin was administered at a dose of 50 mg/kg by oral catheterization one hour prior to thiopental sodium anesthesia. Distilled water was administered with the same method to IIR and Sham groups as a solvent. To induce intestinal ischemia in RIIR and IIR groups, the superior mesenteric artery was suspended from the point where it left the aorta, and ischemia was induced for 45 minutes with the help of an atraumatic microvascular clamp followed by 60 minutes of reperfusion. Biochemical and histopathological examinations were performed on the dissected ileal tissues. Results: The amount of MDA and MPO activity increased, while tGSH levels and CAT activity decreased significantly in the intestinal tissue of the IIR group compared to sham group (P<0.001). Rutin treatment decreased the increase in MDA and MPO activity and increased the decrease of tGSH levels and CAT activity significantly compared to the IIR group (P<0.001). Histopathological changes such as PNL infiltration, edema, hemorrhage, and destruction were observed in the ileal tissue of the rats in the IIR group. However, there were no pathological findings in the RIIR group treated with rutin except for mildly dilated congested blood vessels. Conclusion: Rutin may be useful against intestinal I/R oxidative damage in clinical practice.

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Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models

Huang¹,

Hwang²,

Jia³

et al. 2022

IJMS

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Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen’s Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.

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Effect of Rutin on Cisplatin-induced Small Intestine (Jejunum) Damage in Rats

Cited by 4 publications

References 27 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

Effect of rutin on experimentally induced small intestinal ischemia reperfusion injury in rats: A biochemical and histopathological evaluation

Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models

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