فهرست مطالب sara darakhshan

Despite clinical use, the efficacy of methotrexate is often limited by some adverse effects, mainly nephrotoxicity. The most common mechanism of methotrexate-induced kidney damages is oxidative stress. Harmine as a plant-derived compound has antioxidant and anti-inflammatory properties, The aim of this study was to evaluate the therapeutic effect of harmine, against methotrexate -induced nephrotoxicity.

The mice were divided into six groups: control (saline only); 20 mg/kg methotrexate; 20 mg/kg harmine, and 20 mg/kg methotrexate + harmine at three doses of 5, 10, or 20 mg/kg. Administrations were intraperitoneally and the treatment period was a 14-days. After this time, the sera and kidneys were collected from each group for the following analyses. Samples were analyzed by hematoxylin-eosin (H&E) staining, qRT-PCR, and biochemical assays.

The mice that received methotrexate showed significant increase in creatinine and blood urea nitrogen levels, and 10, or 20 mg/kg harmine mitigated these results. The number and diameter of glomeruli were improved by harmine in methotrexate -treated groups. Moreover, malondialdehyde and nitric oxide levels showed significant increase in the kidney of the mice that received methotrexate, while total antioxidant capacity and superoxide dismutase were diminished. Harmine treatment suppressed oxidative stress markers and also enhanced antioxidant defense parameters. Harmine inhibited methotrexate-induced oxidative stress as shown by the decreased expression of Nqo1, Ho-1, Trx1 and Nrf2 at mRNA level. Harmine also ameliorated histological alterations induced by methotrexate.

Our results suggested that harmine has the potential to protect against methotrexate-induced nephrotoxicity.

Hypertrophic scars are dermal complication that may lead to considerable morbidity. There is an intense medical need for novel therapies for this disease. Tranilast is an anti-allergic agent that clinically used for the treatment of keloids and hypertrophic scars. In this study, we aimed to evaluate the effect of tranilast 0.5% topical formulation on hypertrophic scars resulted by burn injury in rats.

Burn wounds were inflicted on the skin area of the backs of all rats, following that the scars are created, treatment started and continued for 28 days. Animals were divided into two groups (n=8): the control scar group, which received a placebo and the treatment group that received 0.5% tranilast gel. After this period, skin biopsies were collected from each group for the following analyses. The tissue samples were analyzed by hematoxylin-eosin, Masson’s trichrome staining and qRT-PCR.

Histologically, topical tranilast reduced hypertrophic scar signs as compared to placebo. Tranilast treatment also resulted in a reduction in type I and III collagen, transforming growth factor-beta1, Smad2 and vascular endothelial growth factor , and increased Smad7 mRNA expression in the skin scar site.

These findings showed that the 0.5% tranilast topical gel could be effective in the treatment of hypertrophic scars in a rat experiment.

The mercury-induced liver pathogenesis is mainly mediated by oxidative stress. The aim of the current study was to evaluate the possible ameliorative effect of harmine, a natural compound, on liver toxicity induced by mercury chloride (HgCl2).

Forty-two male Balb/c mice were randomly divided into six groups (n = 7): Control, HgCl2 (0.5 mg/kg), harmine (20 mg/kg), and HgCl2 (0.5 mg/kg) + harmine (5, 10, or 20 mg/kg). The mice received treatments once per day for two weeks. After this period, the blood and tissue samples were collected for analyses.

HgCl2 caused a significant increase in levels of hepatic enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase; while harmine ameliorated these effects. Harmine in HgCl2-intoxicated mice, showed protective effects as evidenced by the increase in liver relative weight to body as well as the diameter of central vein in the co-treated group. Serum levels of malondialdehyde and nitric oxide increased in HgCl2, while they were declined in harmine co-treated groups compared to HgCl2 group. The serum level of superoxide dismutase and total antioxidant capacity improved following harmine treatment in the co-administrated group compared to HgCl2 group. Moreover, gene expression analysis demonstrated that harmine treatment improved the HgCl2-induced decreasing of Ho-1, Nrf2, Hqo1, and Trx1. The histopathological examination confirmed the protective effects of harmine.

Mercury can induce toxicity by elevation of oxidative stress in the liver and harmine attenuates hepatic injury induced by HgCl2, at least in part, through its antioxidant activities.

It has been reported that CXCL12 binding to CXCR4 induces several intracellular signaling pathways, and enhances survival, proliferation, and migration of malignant cells. Herein we examined the effects of anti-estrogen tamoxifen and anti-allergic tranilast drugs as a single or in combination on invasion by two in vitro invasion assays, wound-healing and matrigel invasion on MCF-7 and MDA-MB-231 human breast cancer cell lines. The mRNA expression levels of CXCR4 and CXCL12 were measured by quantitative real time-RT PCR and CXCL12 protein levels were evaluated by ELISA assay. The data showed that treatment with tamoxifen and tranilast as a single or in combination resulted in decreased CXCR4 and CXCL12 mRNA and CXCL12 protein expression levels. Both in vitro invasion assays markedly showed synergistic effect of tamoxifen when combined with tranilast drug. Either ER-positive or ER-negative breast cancer cells were sensitive to this combination therapy. In conclusion, tranilast increases antimetastatic effect of tamoxifen. The synergistic effect of tranilast is not estrogen dependent; however tamoxifen may sensitize the cells for the action of tranilast. The data also support the importance of the CXCR4/CXCL12 interaction in breast cancer metastasis, and further suggest that CXCR4 and CXCL12 are critical targets for tamoxifen and tranilast in combination or alone.