ABSTRACT
OBJECTIVES: The objective of this study is to investigate and evaluate the effect of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats with methotrexate (MTX) through biochemical, gene expression, and histopathological examinations. METHODS: Experimental animals were divided into a healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group that received MTX (MTXG). The HREM and HREG groups of rats was administered 50 mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This procedure was repeated for 1 month. At the end of this period, all of the animals were sacrificed with a high dose of anesthesia. Then, the amounts of malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed oropharyngeal tissues. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) gene expressions were measured, and all the tissues were studied histopathologically. RESULTS: The amount of MDA was significantly increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). MTX significantly decreased the amount of tGSH in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers in the animal group in which the levels of MDA, IL-1β, and TNF-α were high and the level of tGSH was low. However, histopathologic examination revealed mucin pools in wide areas due to ruptured oropharynx glands, and proliferated, dilated, and congested blood vessels and dilated ductal structures in some areas. CONCLUSION: HRE protected oropharyngeal oxidative damage induced by MTX. As an inexpensive and natural product, HRE has important advantages in the prevention of oropharyngeal damage induced by MTX.
Subject(s)
Animals , Rats , Anesthesia , Blood Vessels , Estrogens, Conjugated (USP) , Gene Expression , Glutathione , Hippophae , Malondialdehyde , Methotrexate , Mucins , Mucositis , Necrosis , Oropharynx , Stomatitis , Ulcer , WaterABSTRACT
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-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha] and myeloperoxidase [MPO] were also performed. Hematoxylin and eosin-stained paraffinembedded 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 micro mol/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-1beta [40.33 +/- 5.43 gene expression levels], TNF-alpha [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-1beta, TNF-alpha 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