Cardioprotective effects of sodium thiosulfate against doxorubicin-induced cardiotoxicity in male rats.

BACKGROUND: Doxorubicin (DOX) is an effective antitumor agent, but its clinical usage is limited due to adverse cardiotoxic effects. Several compounds have been studied to reduce DOX cardiotoxicity to improve its therapeutic index. This study was aimed to investigate the protective effects of sodium thiosulfate (STS) pre-treatment against DOX-induced cardiomyopathy in rats. METHODS: Male Wistar rats were randomized into 4 groups: control (saline), DOX (2.5 mg/kg, 3 times per week, intraperitoneal [i.p.]), STS (300 mg/kg, 3 times per week, i.p), and DOX + STS (30 min prior to DOX injection, 3 times per week, i.p.) over a period of 2 weeks. The body weight, electrocardiography, histopathology, papillary muscle contractility, and oxidative stress biomarkers in heart tissues were assessed. RESULTS: The results indicated that STS significantly improved the body weight (P < 0.01), decreased QRS complex and QT interval on ECG (P < 0.05 and P < 0.001, respectively), as well as declined the papillary muscle excitation, and increased its contraction (P < 0.01) compared to DOX-treated rats. STS strongly suppressed oxidative stress induced by DOX through the significant improvement of the cardiac tissue antioxidant capacity by increasing glutathione, superoxide dismutase (P < 0.001), and decreasing the level of lipid peroxidation (P < 0.01). CONCLUSION: Taken together, the results of this study demonstrated that STS showed potent cardioprotective effects against DOX-induced cardiotoxicity by suppressing oxidative stress.

Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition.

PURPOSE: Glioblastoma multiforme (GBM) is one of the most aggressive human cancers. The c-MET receptor tyrosine kinase (RTK) which is frequently deregulated in GBM is considered as a promising target for GBM treatment. The c-MET plays a key role in cell proliferation, cell cycle progression, invasion, angiogenesis, and metastasis. Here, we investigated the anti-tumour activity of foretinib, a c-MET inhibitor, on three human GBM cells (T98G, U87MG and U251). METHODS: Anti-proliferative effect of foretinib was determined using MTT, crystal violet staining, and clonogenic assays. PI and Annexin V/PI staining flow cytometry were used to evaluate the effects of foretinib on cell cycle and apoptosis, respectively. Scratch assay, qRT-PCR, western blot, and zymography analyses were applied to elucidate the molecular mechanisms underlying the anti-tumour activity of foretinib. RESULTS: Foretinib treatment reduced phosphorylation of c-MET on T98G and U251 cells, but not in U87MG cells. The highest inhibitory effect was observed in T98G cells (IC50 = 4.66 ± 0.29 µM) and the lowest one in U87MG cells (IC50 = 29.99 ± 1.31 µM). The results showed that foretinib inhibited the proliferation of GBM cells through a G2/M cell cycle arrest and mitochondrial-mediated apoptosis in association with alternation in expression of the related genes and protein-regulated G2/M phase and apoptosis. Foretinib diminished GBM cell invasion through downregulation of the proteolytic cascade of MMP2, uPA and uPAR and epithelial-mesenchymal transition (EMT)-related genes. A different GBM cell sensitivity pattern was noticeable in all experiments which demonstrated T98G as a sensitive and U87MG as a resistant phenotype to foretinib treatment. CONCLUSION: The results indicated that foretinib might have the therapeutic potential against human GBM which deserve further investigation.

A study of difference in serum 25-hydroxyvitamin D concentrations in patients with angiographically-defined coronary disease and healthy subjects.

BACKGROUND: Cardiovascular disease (CVD) is one of the most important causes of death in developing countries. The current study evaluates the serum 25-hydroxyvitamin D (25OHD), phosphate and calcium levels in patients with angiographically-defined coronary artery disease (CAD) and healthy subjects in a sample population in northeastern Iran. METHODS: There were 566 subjects aged between 20-80 years out of whom283 subjects with CAD were divided into two study groups based on their angiogram results; those with > 50% stenosis of one or more coronary arteries and those with ≤ 50% stenosis. Serum 25OHD levels and anthropometric parameters were measured for all subjects. RESULTS: There were approximately 53% (n = 303) males and 47% (n = 269) females in the population sample. We found that crude serum 25OHD concentrations were significantly higher in both the Angio- (21.6 ±â€¯11.8 ng/ml) and Angio+ (21.3 ±â€¯10.2 ng/ml) groups compared to the control subjects (16.4 ±â€¯9.5 ng/ml) (P < 0.001). CONCLUSION: The findings show that 25OHD state could be a risk factor for CAD, although this would need to be explored further, taking the potential confounding effects of diet into account in future studies.