Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats

Kurt, Nezahat/0000-0002-1685-5332; Arslan, Aynur/0000-0001-5968-5823WOS: 000361557500026PubMed: 26379839The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. the rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. the rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion

Protective effects of Rutin against methanol induced acute toxic optic neuropathy: an experimental study

AIM: To determine the effects of Rutin on methanol induced optic neuropathy and compare the results with the effects of ethanol. METHODS: Totally 30 rats were divided into 5 groups, with 6 rats in each group as follows: healthy controls (C), methotrexate (MTX), methotrexate+methanol (MTM), methotrexate+methanol+ethanol (MTME) and methotrexate+ methanol+Rutin (MTMR). In all rabbits except those of the control group, MTX, diluted in sterile serum physiologic, 0.3 mg/kg per oral was applied for 7d by the aid of a tube. After this procedure to the rats of MTM, MTME and MTMR groups, 20% methanol with a dose of 3 g/kg per oral was given by the aid of a tube. In MTME group, 4h after the application of methanol, 20% ethanol was applied by the same way with a dose of 0.5 g/kg. On the other hand, in MTMR group 4h after the application of methanol, Rutin, which was dissolved in distilled water, was applied by the same way with a dose of 50 mg/kg. RESULTS: There were statistically significant differences in tissue 8- hydroxy-2 deoxyguanine (8-OHdG), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO). glutathione peroxidase (tGSH) and superoxide dismutase (SOD) levels between groups (P<0.001). In MTMR group tissue 8-OHdG, IL-1β, MDA, and MPO levels were similar with the healthy controls but significantly different than the other groups. In histopathological evaluations, in MTX group there was moderate focal destruction, hemorrhage and decrease in number of astrocytes and oligodendrocytes; in MTM group there was severe destruction and edema with decrease in number of astrocytes and oligodendrocytes; in MTME group there was mild hemorrhage, mild edema, mildly dilated blood vessels with congestion while in MTMR group, optic nerve tissue was resembling the healthy controls. CONCLUSION: Rutin may prevent methanol-induced optic neuropathy via anti-inflammatory effects and decreasing the oxidative stress. New treatment options are warranted in this disease to avoid loss of vision in patients

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

Arslan, Aynur/0000-0001-5968-5823; Cetin, Nihal/0000-0003-3233-8009;WOS: 000387526400001PubMed: 27333839Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. the control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. the duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide