TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

Silymarin inhibits cell cycle progression and mTOR activity in activated human T cells: therapeutic implications for autoimmune diseases.

Silymarin, a complex flavonolignan from the 'milk thistle' (Silybum marianum) plant, exhibits anticarcinogenic, anti-inflammatory and cytoprotective effects. Several reports have demonstrated immunosuppressive activity of silymarin; however, the molecular mechanisms involved in immunomodulatory activities of silymarin are not fully understood yet. In this study, the effect of silymarin on cell cycle and PI3K/Akt/mTOR signalling pathway of activated T lymphocytes was investigated in vitro. Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers and activated with anti-CD3 (5 µg/ml) and anti-CD28 (2 µg/ml) monoclonal antibodies. Cells were cultured in Complete RPMI medium with 10, 50 and 100 µM silymarin or dimethyl sulphoxide (DMSO) and incubated for 24-96 hrs. Cell cycle analysis was performed by PI staining and flow cytometry. The effect of silymarin on PI3K/AKT signalling pathway and mTOR activity was determined in activated T cells after 72-hr incubation with silymarin or DMSO. A significant G1 arrest in cell cycle of activated T lymphocytes was found after 96-hr incubation with 100 µM silymarin without causing cell death. Silymarin also significantly inhibited the level of phospho-S6 ribosomal protein and mTOR activity in cell lysates of activated T cells after 72-hr incubation in comparison with DMSO. This study shows that silymarin inhibits cell proliferation through G1 cell cycle arrest and also through the suppression of the mTOR signalling pathway in human activated T lymphocytes in vitro. Characterizing molecular mechanism of such immunomodulatory effects may have a great potential in future practical application of silymarin in transplantation and auoimmunity.

Adenosine A2A receptors and uric acid mediate protective effects of inosine against TNBS-induced colitis in rats.

Inflammatory bowel disease comprises chronic recurrent inflammation of gastrointestinal tract. This study was conducted to investigate inosine, a potent immunomodulator, in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced chronic model of experimental colitis, and contribution of adenosine A(2A) receptors and the metabolite uric acid as possible underlying mechanisms. Experimental colitis was rendered in rats by a single colonic administration of 10 mg of TNBS. Inosine, potassium oxonate (a hepatic uricase inhibitor), SCH-442416 (a selective adenosine A(2A) receptor antagonist), inosine+potassium oxonate, or inosine+SCH-442416 were given twice daily for 7 successive days. At the end of experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1beta (IL-1ß) levels, and myeloperoxidase (MPO) activity were assessed. Plasma uric acid level was measured throughout the experiment. Both macroscopic and histological features of colonic injury were markedly ameliorated by either inosine, oxonate or inosine+oxonate. Likewise, the elevated amounts of MPO and MDA abated as well as those of TNF-α and IL-1ß (P<0.05). SCH-442416 partially reversed the effect of inosine on theses markers, while inosine+oxonate showed a higher degree of protection than each treatment alone (P<.0.05). No significant difference was observed between TNBS and SCH-442416 groups. Uric acid levels were significantly higher in inosine or oxonate groups compared to control. Inosine+oxonate resulted in an even more elvelated uric acid level than each treatment alone (P<0.05). Inosine elicits notable anti-inflammatory effects on TNBS-induced colitis in rats. Uric acid and adenosine A(2A) receptors contribute to these salutary properties.

Abortifacient effect of Prangos ferulacia on pregnant rats.

PURPOSE: Prangos ferulacea grows in southern Iran and used in Iranian herbal medicine for gastrointestinal disorders, but it seems it has an abortifacient effect on pregnant women. To verify its potential as an abortifacient agent, we administered the leaves of this plant to pregnant rats. MATERIAL AND METHODS: Hydroalcoholic and aqueous extract of the leaves was administered orally at different doses to 60 rats on the first 18 days of pregnancy. Group 1 (G1) was considered as control group and was given only water. Groups 2-5 (G2-G5) received 25, 50, 100 mg/g per day and Groups 6-8 (G6-G8) received 300, 500 and 1000 mg/g per day, respectively. On Day 18 of pregnancy, they were killed and laparotomized. The uterine horns of each group were opened to see whether they contained any live and degenerated/dead fetuses. We used Student's t-test to analyze the data (p < or = .05 was considered significant). RESULTS: Of the total 504 fetuses in the studied groups, 13 fetuses (2.57%) were aborted. The abortion rate in the control group was 2 (1.94%) of 103 fetuses; the abortion rate was higher in the treated groups but not statistically significant. There was no relationship between the dose and type of extract and abortion rate in all studied groups. CONCLUSION: This study shows that the aqueous or hydroalcoholic extract of P. ferulacea is ineffective on the rate of abortion of pregnant rats. Future studies should be performed with higher doses to test the efficacy of this agent on other animals.