The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression

Abstract

Objective: The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue. Materials and Methods: Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA. Results: The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 μmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1β (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1β, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group. Conclusion: In this study, ileal damage caused by MTX was inhibited by RST.

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

“…Previous studies have demonstrated that various organs, such as the liver, brain, kidney and lung, in F2 hybrid mice appear to have oxidative DNA damage with aging (12,16,17). However, the oral absorption of resveratrol may reduce the high levels of oxidative damage markers induced by aging (18). Therefore, the aim of the present study was to investigate the protective effects of resveratrol in a rat model of osteoporosis and examine the associated mechanisms of its action.…”

Resveratrol Siçanlarda Oksi̇dati̇f Stresi̇ Ve Apoptozu Baskilayarak Metotreksat Kaynakli Yumurtalik Hasarini Hafi̇fleti̇r

“…Many studies have examined the use of RES as a therapeutic agent to treat various pathological and metabolic disorders (15). In previous studies, the protective effects of resveratrol on MTX-induced liver damage (29), intestinal damage (30,31) and ileum damage (32) has been reported.…”

Impact of the induction phase chemotherapy on cytokines and oxidative markers in peripheral and bone marrow plasma of children with acute lymphocytic leukemia

“…These findings suggest that positive MRD status, i.e., the presence of residual treatment-resistant tumor cells at the end of the treatment may be required for the production of lipoperoxides observed in this study. MRD occurs significantly in some cases of ALL ( Ozcicek et al, 2016 ) and its assessment is primordial to classify the risk of patient relapse at this stage ( Li et al, 2009 ). An in vitro study ( Reddy et al, 2011 ) identified that oxidative stress generation in mitochondria is linearly correlated with chemotherapeutic resistance in acute lymphoblastic leukemia, which allows for redox adaptation and an increase in MRD in patients.…”