Effect of lutein on methotrexate-induced oxidative lung damage in rats: a biochemical and histopathological assessment

BACKGROUND/AIMS@#This study aimed to investigate the effect of lutein on methotrexate (MTX)-induced pulmonary toxicity in rats biochemically and histopathologically.@*METHODS@#The rats in the MTX + lutein (MTXL, n = 6) group were given 1 mg/kg of lutein orally. A 0.9% NaCl solution was administered orally to the MTX (n = 6) group and the healthy group (HG, n = 6). One hour later, a single 20 mg/kg dose of MTX was injected intraperitoneally in the MTXL and MTX. Lutein or 0.9% NaCl solution was administered once a day for 5 days. At the end of this period, malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) were measured in the lung tissues from the animals euthanized with 50 mg/kg thiopental sodium anesthesia. Subsequently, histopathological examinations were performed.@*RESULTS@#The levels of MDA, MPO, IL-1β, and TNF-α in the lung tissue of the MTX were significantly higher than those of the MTXL and HG groups (p < 0.0001), and the amount of tGSH was lower. The histopathological findings in the MTX group, in which the oxidants and cytokines were higher, were more severe.@*CONCLUSIONS@#Lutein prevented the MTX-induced oxidative lung damage biochemically and histopathologically. This result indicates that lutein may be useful in the treatment of MTX-induced lung damage.

Effect of Hippophae rhamnoides Extract on Oxidative Oropharyngeal Mucosal Damage Induced in Rats Using Methotrexate

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.

Effect of etoricoxib on experimental oxidative testicular ischemia-reperfusion damage in rats induced with torsion-detorsion

Etoricoxib features antioxidant and anti-inflammatory properties concomitantly, suggesting that it may be beneficial in testicular ischemia reperfusion (I/R) damage. Our aim is to investigate the effects of etoricoxib on testicular I/R damage induced with torsion-detorsion (TD). The etoricoxib + torsion-detorsion (ETD) groups of animals were given etoricoxib in 50 and 100 mg/kg of body weight (ETD-50 and ETD-100), while the testes torsion-detorsion (TTD) and sham operation rat group (SOG) animals were given single oral doses of distilled water as a solvent. TTD, ETD-50 and ETD-100 groups were subjected to 720° degrees torsion for four hours, and detorsion for four hours. The SOG group was not subjected to this procedure. Biochemical, gene expression and histopathological analyses were carried out on the testicular tissues. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were significantly higher, and the levels of total glutathione (tGSH) and glutathione reductase (GSHRd) were significantly lower in the TTD group, compared to the ETD-50, ETD-100 and SOG groups. Etoricoxib at a dose of 100 mg/kg better prevented I/R damage than the 50 mg/kg dose. Etoricoxib may be useful in clinical practice in the reduction of I/R damage on testes caused by torsion-detorsion.

impact of resveratrol on oxidative stress induced by methotrexate in rat ileum tissue: evaluation of biochemical and histopathological features and analysis of gene expression

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