Efficacy of royal jelly on methotrexate-induced systemic oxidative stress and damage to small intestine in rats

Abstract

The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1 st group as placebo for 10 days and MTX (20 mg/kg, intraperitoneal: ip) on the 7 th day. The 2 nd group received RJ (50mg/kg, po) for 10 days and normal saline (NS) instead of MTX. RJ (50mg/kg) was given to the 3 rd group for 10 days and MTX on the 7 th day. The 4 th group received RJ (100 mg/kg, po) for 10 days and NS was given intraperitoneally. RJ (100mg/kg) was given to the 5 th group for 10 days and a single dose of MTX. Distilled water was given to the 6 th (control) group for 10 days and intraperitoneal NS on the 7 th day. Malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase were analyzed in blood samples on the 11 th day. Morphological and histopathological changes were examined in the intestinal tissue samples. Villus length and mucosal thickness, as well as the villus length/crypt ratio, were significantly decreased with MTX administration, and the semiquantitative histological evaluation (SQHE) score was measured high (p<0.001). In addition, a decrease in the antioxidant parameters and an increase in the MDA levels were identified. The villus length and SQHE were significantly different in the groups receiving RJ (p<0.001) as compared to the MTX group. Although RJ addition had no effect on the decreased mucosal thickness and villus/crypt ratio in MTX groups, it caused an improvement in the antioxidant levels and a remarkable decrease in MDA levels. Adding RJ has a decreasing effect on the MTX-induced intestinal damage and it has a suppressive effect on MTX-induced oxidative stress by means of increasing antioxidant enzyme activity and decreasing lipid peroxidation.

Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

“…Kaynar et al demonstrated that oxidant parameters were increased and antioxidant parameters decreased in small intestines of the rats administered MTX, in addition reported marked villus and crypt epithelial damage, mixed inflammatory cell infiltration containing PMNL and eosinophil leukocytes [12]. MTX was reported to cause hyperemia, inflammatory cell infiltration and loss of villus epithelial cells in the small intestines of rats [6].…”

“…Kolli et al reported that, oxidants such as malondialdehyde (MDA) which is a product of lipid peroxidation and MPO which is the marker of neutrophil activation and infiltration increase, while the levels of non-enzymatic and enzymatic antioxidants such as glutathione (GSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), glutathione s-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) decrease in MTX induced small intestine mucositis [13]. Elevation in the oxidant parameters and reduction in the antioxidant parameters in duodenal and jejunal tissues given MTX have also been emphasized in the experimental trials by Kaynar et al and Gulgun et al [9, 12]. …”

Complementary Therapies in the Management of Induced Oral Mucositis during Cancer Treatment

“…Klinik öncesi araştırma sonuçları; arı sütünün antioksidan etki sağla-dığını ve topikal olarak uygulanan arı sütünün oral mukozit tedavisinde kullanılabileceğini destekler niteliktedir. [67,68] Klinik araştırmalar incelendiğinde; arı sütünün oral mukozit yöneti-minde etkisini değerlendiren iki çalışmaya rastlanmıştır. Farklı kanser türlerinde kemoterapi ve radyoterapi alan hastalarla yü-rütülen yarı deneysel bir araştırmada, hastalardan günlük doz 1 gram olacak şekilde günde iki kez 30 saniye boyunca arı sütü ile ağızlarını çalkalamaları ve yutmaları istenmiştir, araştırma sonucunda standart bakıma ek olarak uygulanan arı sütünün oral mukozit iyileşme süresini kısalttığı belirtilmiştir.…”

Steamed root of Rehmannia glutinosa Libosch (Plantaginaceae) alleviates methotrexate-induced intestinal mucositis in rats

“…The remnant jejunum was rinsed with ice-cold 0.1 m phosphate buffer solution (PBS, pH 7.2), and the mucosa was collected by scraping and homogenized in 10 times the volume of icecold PBS using a glass homogenizer. After centrifugation (4°C, 1000 g, 10 min), the homogenate was stored at À 80°C for the determinations of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and tumor necrosis factor alpha (TNF-α) (see details below) (Kaynar et al, 2012;Leblond et al, 2008;Logan et al, 2007).…”

“…In the present study, a rat model of chemotherapy-induced intestinal mucositis was established by intraperitoneal administration of methotrexate (MTX), an inhibitor for dihydrofolate reductase commonly used as a chemotherapeutical agent (Fijlstra et al, 2013;Kaynar et al, 2012;Kolli et al, 2008;Maeda et al, 2010). The effect of SRR on the alleviation of the adverse effects of high-dose MTX was evaluated in comparison to the effect of calcium folinate (CF), a clinical antidote of MTX (Fan et al, 2011a;2011b;Madhyastha et al, 2008) and the combined effect of SRR plus CF.…”