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

Amelioration of oxidative damage parameters by carvacrol on methanol-induced liver injury in rats

The methanol metabolite that causes hepatotoxicity is formic acid, generating reactive oxygen radical formation and cell damage. Carvacrol is an antioxidant monoterpenic phenol produced from Thymus vulgaris. This study aimed to investigate the effects of carvacrol on methanol-induced oxidative liver damage in rats. Eighteen rats were divided into three groups. Methotrexate was administered orally for 7 days to methotrexate+methanol (MTM) and methotrexate+methanol+carvacrol (MMC) groups. Methotrexate was given before methanol to cause methanol poisoning. Distilled water was given to the healthy group (HG) as a solvent. At the end of the 7th day, 20% methanol was administered orally at a dose of 3 g/kg to the MTM and MMC groups. Four hours after methanol administration, 50 mg/kg carvacrol was injected intraperitoneally into the MMC group. Animals were sacrificed 8 h after carvacrol injection. Biochemical markers were studied in the excised liver tissue and blood serum samples, and histopathological evaluations were made. Severe hemorrhage, hydropic degeneration, pycnosis, and mononuclear cell infiltration were observed in the liver of the MTM group. Additionally, the levels of malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly higher, and total glutathione (tGSH) and total antioxidant status (TAS) were significantly lower in the MTM group compared to HG (P<0.001). Carvacrol prevented the increase in MDA, TOS, ALT and AST levels with methanol and the decrease in tGSH and TAS levels (P<0.001), and alleviated the histopathological damage. Carvacrol may be useful in the treatment of methanol-induced liver damage

Effects of Mirtazapine on Liver Ischemia-Reperfusion Injury in Rats

Background and Objective: Ischemia-reperfusion (I/R) injury begins with tissue oxygen deprivation and continues with oxidative stress and inflammatory response. Mirtazapine is an antidepressant drug with antioxidant and anti-inflammatory properties. The current study was to investigate the effect of mirtazapine against I/R induced liver injury in rats. Materials and Methods: Albino Wistar-type male rats were divided into sham operation (SHAM), I/R (IR) and I/R+mirtazapine administrated (IRM) groups. One hour before anaesthesia, 20 mg kg(-1) mirtazapine was administered to the IRM group of the animals and distilled water was applied to the SHAM and IR groups as a solvent. I/R was achieved by clamping the hepatic artery (except for the SHAM group). Following I/R, all rat groups were killed with high-dose anaesthesia. Malondialdehyde (MDA), total glutathione (tGSH), nuclear factor kappa B (NF-kappa B), interleukin 1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) were determined in liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in blood serum. In addition, histopathological examination was performed on liver tissue samples. Results: Mirtazapine prevented increased levels of MDA, NF-kappa B, IL-1 beta, TNF-alpha, ALT and AST in liver tissue with I/R and a decrease in tGSH. Furthermore, mirtazapine has alleviated I/R-associated severe hepatocyte degeneration, necrosis and other structural disorders in the liver. Conclusion: Biochemical and histopathological experimental results suggest that mirtazapine may be useful in the treatment of I/R-induced liver injury

Everolimus-Induced Oral Mucositis Can be Prevented by Hippophae Rhamnoides Extract in Rats

Objectives: Oral mucositis is a significant toxicity related to the mammalian target of rapamycin inhibitor everolimus.Oxidative stress and pro-inflammatory cytokines, which contribute to treatment-related mucositis, can betargeted with Hippophae rhamnoides extract (HRE). Herein, we assessed the effects of HRE on everolimus-inducedmucositis in rats.Methods: Eighteen rats were equally divided into healthy, everolimus, and everolimus plus HRE groups. Malondialdehyde(MDA) and total glutathione (tGSH) levels along with interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha(TNF-α) gene expression levels were measured in the tongue and buccal mucosa tissues of all groups, histopathologicalchanges were also evaluated. We tested the significance of variations with one-way variance analysis. We also analyzedthe differences between groups with Kruskal–Wallis test and Mann–Whitney U-test.Results: HRE significantly decreased MDA and increased tGSH levels and reduced IL-1β and TNF-α gene expression inboth tissues administered everolimus (p&lt;0.001 for each). Histological examination revealed that HRE improved epithelialformation and keratinization, disrupted by everolimus, and alleviated everolimus-related mononuclear cell infiltration(p&lt;0.05 for each).Conclusion: In light of these results, HRE may be a promising agent to manage oral mucositis caused by everolimus,given the lack of effective therapeutic options for this type of adverse event.Keywords: Everolimus, hippophae rhamnoides, oral mucositis</p