Ozone ameliorates methotrexate-induced intestinal injury in rats

Abstract

Methotrexate (Mtx) is an effective chemotherapeutic agent used in various cancer treatments. Gastrointestinal toxicity is the drug's major limiting factor, arising mainly from oxidative damage. It has been proposed that ozone (O(3)) is an activator of antioxidant enzymes. Thus, this study was designed to investigate the efficacy of ozone therapy in the prevention of Mtx-induced intestinal injury in rats. Twenty rats were allocated into three groups: sham, Mtx alone (untreated) and Mtx + O(3) (treated with ozone). Ozone was administered at a dose of 0.72 mg/kg daily via an intraperitoneal route for 15 d. On d 16, Mtx was applied via an intraperitoneal injection at a dose of 6 mg/kg for 5 d. All rats were sacrificed at d 21. Efficacy of the treatment was assessed by measuring the histopathologic injury score (HIS), and biochemically by determining tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in ileum, liver and kidney homogenates. Although two rats (25%) died in the untreated group, all rats in the sham and treatment groups survived the study. The HIS, antioxidant enzyme and MDA levels of the ileal tissue were significantly lower in the ozone treated group than the untreated group (p < 0.05). Although the antioxidant enzyme and MDA levels of liver and kidney were significantly lower in the ozone treated group (p < 0.05), there was no significant change in histopathology (p > 0.05). Thus, ozone preconditioning shows a preventative effect in the ileum by decreasing tissue damage and increasing antioxidant enzyme activity in an experimental model of Mtx-induced intestinal injury.

Effects of Polyphenols from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) on Methotrexate-Induced Intestinal Injury in Rats

“…Our results revealed that MTX induced severe morphological intestinal injury and increase in the level of lipid oxidation marker, MDA, and decrease in the levels of the antioxidant markers, GSH and GSH-Px, similarly to previous studies [12,16,25,29]. JHP supplementation ameliorated the MTX-induced morphological intestinal injury and preserved intestinal MDA, GSH and GSH-Px levels.…”

“…MTX reportedly causes morphological intestinal injury associated with oxidative damages [12,16,20,29]. Our results revealed that MTX induced severe morphological intestinal injury and increase in the level of lipid oxidation marker, MDA, and decrease in the levels of the antioxidant markers, GSH and GSH-Px, similarly to previous studies [12,16,25,29].…”

“…It was also demonstrated that MTX caused a significant reduction in antioxidant protein and enzyme levels and an increase in levels of oxidant markers such as malondialdehyde (MDA) [12,16,25,29]. Therefore, In order to minimize side-effects of MTX in patients, the studies focused on antioxidants [12,16,25,29,32].Many polyphenols are known to be antioxidants, and the possibility exists that they protect against oxidative damage by directly neutralizing reactive oxidants [8,14,21,22,24,30]. However, to our knowledge, there are no reports showing the protective effects of polyphenols from seed shells of Japanese horse chestnut (JHP) against oxidative stressrelated pathologic conditions in vivo.…”

“…It was also demonstrated that MTX caused a significant reduction in antioxidant protein and enzyme levels and an increase in levels of oxidant markers such as malondialdehyde (MDA) [12,16,25,29]. Therefore, In order to minimize side-effects of MTX in patients, the studies focused on antioxidants [12,16,25,29,32].…”

The Effectiveness of Grape Extract in Rats with Methotrexate Induced Intestinal Mucositis

“…In order to minimize side-effects of MTX in patients, the studies focused on antioxidants. [28][29][30][31] One of them, GE, was mostly emphasized on its antioxidant properties in a number of in vitro and in vivo studies. 17,32,33 Various studies also presented that GE has been tried in the repair of MTX-induced intestinal injury.…”