Toxicological evaluation and anti-inflammatory activity of a golden gelatinous sorghum bran extract.

Golden gelatinous sorghum (GGS) is rich in phytochemicals and anti-oxidants. We investigated the toxicity and anti-inflammatory properties of a GGS extract. We observed no toxic effects after a daily dose of up to 5000 mg/kg body weight of the GGS extract administered orally to rats for 14 d. The exposure of mice ears to 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a marked increase in ear thickness, which was significantly inhibited by treating with the GGS extract; this inhibition of inflammatory response was clearly confirmed by a histological analysis. The TPA-induced mice ear edema model, indicated that treating with the GGS extract inhibited the expression levels of such inflammatory mediators as cyclooxygenase-2 and inducible nitric oxide synthase. The nitric oxide level in lipopolysaccharide (LPS)-induced Raw264.7 cells in vitro was lower in the GGS extract-treated group than in the LPS-only treated group. These results suggest that sorghum would be a safe, nontoxic product, and that the GGS extract possessed significant anti-inflammatory activity.

Cardioprotective effects of 3-phosphoinositide-dependent protein kinase-1 on hypoxic injury in cultured neonatal rat cardiomyocytes and myocardium in a rat myocardial infarct model.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) is involved in numerous cellular responses. In this study, we investigated the protective effects of PDK1 gene expression against hypoxic conditions in cultured rat CMCs (rCMCs) and in a rat myocardial infarction (MI) model using the lentiviral vector (LeV) system. LeV-PDK1 transfer effectively reduced the apoptotic cell death caused by hypoxic injury as compared to LeV-GFP transfer in rCMCs the expression of survival proteins increased in the LeV-PDK1 group, whereas apoptosis signaling decreased in the rCMCs and in infarcted hearts treated with LeV-PDK1. LeV-PDK1 transfer also reduced apoptosis and infarct size and attenuated myocardial wall thinning and ventricular remodeling in a rat MI model. These findings suggest that PDK1 has a protective role in the injured ischemic myocardium via overexpression of the cell survival pathway in CMCs. Hence PDK1 can be used as a treatment strategy for myocardial salvage inin hypoxic injury.

The PPARγ agonist protects cardiomyocytes from oxidative stress and apoptosis via thioredoxin overexpression.

Oxidative stress has been implicated in the pathogenesis of various cardiovascular diseases, including ischemic heart disease and heart failure. The peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves insulin sensitivity and limits tissue inflammation and cellular apoptosis, but there are few data on the relationship between the PPARγ agonist, rosiglitazone (RSG), and the thioredoxin (TRx) system in oxidatively stressed cardiomyocytes (CMCs). Here we provide evidence that the PPARγ agonist RSG protects rat CMCs from hydrogen peroxide (H2O2)-induced apoptosis by TRx overexpression. The expression levels of pAkt/Akt, pErk/Erk, survivin, Bcl-2/Bax-α, and manganese-superoxide dismutase were increased by RSG pretreatment in H2O2-injured rat CMCs. On the contrary, the expression levels of caspase-3 and p53 were decreased by RSG pretreatment. These effects of RSG were reversed by chemical inhibitors of TRx and the PPARγ antagonist. This suggests that RSG protects rCMCs from H2O2-induced oxidative stress through TRx overexpression and a PPARγ-dependent mechanism.

Serum thioredoxin 1 level has close relation with myocardial damage amount in acute myocardial infarction patients.

Thioredoxin-1 (Trx-1) is one of important anti-oxidative molecules to overcome the oxidative stress. The aim of the present study is to investigate the clinical relationship between serum concentration of Trx-1 on the pre-percutaneous coronary intervention (prePCI) and myocardial damage amount in the patients with acute myocardial infarction with the culprit lesion in only the left anterior descending artery on coronary angiography (n = 100). Initial value of creatine kinase (CK) was 368.3 ± 531.4 U/L, and MB isoenzyme of CK (CK-MB) level was 22.92 ± 33.8 ng/mL, and cardiac specific troponin T (cTnT) level was 0.61 ± 1.6 ng/mL. Positive correlations were observed between prePCI Trx-1 level and initial CK (P = 0.005, r = 0.281), and cTnT (P < 0.001, r = 0.453), peak CK (P = 0.001, r = 0.316) in all patients, but the statistical relation was observed only in ST segment elevation myocardial infarction (STEMI) patients (P = 0.008, r = 0.329 for initial CK, P = 0.001, r = 0.498 for initial cTnT, P = 0.005, r = 0.349 for peak CK), not in Non-STEMI patients. Conclusively, we consider prePCI serum Trx-1 as a predictor for myocardial damage amount in patients with STEMI.

Modifying effect of diallyl sulfide on colon carcinogenesis in C57BL/6J-ApcMin/⁺ mice.

Diallyl sulfide (DAS), a flavoring compound derived from garlic, is considered to have cancer chemopreventive potential in experimental animals and humans. This study was designated to examine possible chemopreventive effects of DAS on colon carcinogenesis using genetically engineered transgenic ApcMin/⁺ mice, a well-established animal model for familial adenomatous polyposis (FAP) and sporadic colorectal cancer. Male C57BL/6J-ApcMin/⁺ mice were divided into three groups. Animals of group 1 were placed on the basal diet (AIN-76A) as non-treated controls. Animals of groups 2 and 3 were given DAS- containing diets (in doses of 100 and 300 ppm, respectively). All mice were sacrificed at the end of week 10 of the experiment. Histopathological investigation revealed that the incidence of colonic polyps was decreased dose-dependently by 19% (13/16) in group 2 and by 32% (13/20) in group 3 compared to the 100% incidence (10/10) in group 1. The multiplicity of colonic polyps per mouse was also slightly decreased by DAS treatment (1.88 ± 0.35 in group 2 and 1.63 ± 0.36 in group 3) compared to 2.00 ± 0.39 in group 1. On the other hand, there were no significant differences in the numbers of total polyps per mouse in the small intestine between the groups. Taken together, we suggest that DAS may exert promising inhibitory effects on colon carcinogenesis in the transgenic ApcMin/⁺ mice.

Comparison of bare metal stent and paclitaxel-eluting stent using a novel rat aorta stent model.

The purpose of our study was to create a novel rat aorta stent implantation model. Stainless steel bare metal stents (BMS) or paclitaxel-eluting stents (PES) were implanted in male Sprague-Dawley rats (BW 400 ± 20 g). Two and four weeks after stent implantation, the aorta were collected, fixed with 2% glutaraldehyde, and cut into two segments. One segment was used for scanning electron microscopy analysis to evaluate re-endothelialization, and the other segment was used to calculate the neointimal area. At 2 weeks after stenting, the appearance of neointimal hyperplasia was less in the PES group than in the BMS group. At 4 weeks after stenting, no significant difference in neointimal hyperplasia was observed between two groups. On the other hand, the PES group showed more thrombus formation and less re-endothelialization compared to the BMS group. This study demonstrated the ability of a novel rat model of aorta stenting via a common carotid artery to measure the efficacy and safety of commercially available drug-eluting stents.