Histone deacetylase inhibitors: a novel class of therapeutic agents in diabetic nephropathy

Histone deacetylase (HDAC) inhibitors are currently being tested as anticancer agents in clinical trials. Chromatin remodeling, such as through histone acetylation, is a fundamental phenomenon in eukaryotic cell biology, bearing implications to numerous physiological and pathological phenomena. Here, we discuss recent data from our own laboratory and those of others demonstrating antifibrotic and renoprotective effect of HDAC inhibitors in diabetic kidneys, and the possible mechanisms including the role of reactive oxygen species. HDAC inhibitors may prove to be a novel class of multitarget agents in the treatment of diabetic nephropathy.     

Yoga Training Improves Metabolic Parameters in Obese Boys

Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.     

Development and validation of an LC–ESI–MS/MS method for simultaneous determination of levodopa, dopamine, L-α-methyldopa and 3-O-methyldopa in rat plasma

Parkinson??s disease (PD) is a progressive degenerative disorder of the central nervous system. Levodopa (L-dopa), dopamine precursor is the most effective therapeutic drug for PD patients. Levodopa (LDP) and its three metabolites in rat plasma were determined using high performance liquid chromatography coupled with tandem mass spectrometry (LC?CMS/MS). Method validation was conducted in terms of linearity, accuracy, precision, recovery, specificity, limit of detection, limit of quantification and stability. Correlation coefficients (r ²) were above 0.9965. The intra-day accuracy values at LLOQ (low limit of quantification), LQC (low quality control), MQC (medium quality control) and HQC (high quality control) levels were 85.7?C103.3, 96.5?C105.1, 90.7?C100.1 and 94.2?C101.3?%, respectively. The inter-day accuracy values at LLOQ, LQC, MQC and HQC levels were 77.6?C112.0, 91.1?C109.3, 84.3?C101.0 and 88.2?C103.9?%, respectively. The coefficient of variation (RSD) values of both intra- and inter-day results were within 6.7 and 8.5?%, respectively. The recoveries (mean?±?%SD) for LLOQ, LQC, MQC and HQC were 82.7?±?3.7?C113?±?2.8?%, 86.6?±?5.7?C110.3±3.4?%, 90.9?±?3.6?C106?±?6.5 and 89.7?±?4.5?C97.4?±?6.7?%, respectively. The coefficient of variation (RSD) values of both intra- and inter-day results were within 6.7 and 8.5?%, respectively. The validated LC?CMS/MS method was applied successfully to the measurement of LDP and its metabolites in the rat plasma samples.     

Momilactone B,an Allelochemical of Rice Hulls,Induces Apoptosis on Human Lymphoma Cells (Jurkat) in a Micromolar Concentration

Although momilactone B has been studied as an allelochemical of rice (Oryza sativa L.), to date we have no report showing the effect of momilactone B on mammalian cells. This study was undertaken to examine whether this allelochemical has anticancer activity on cancer cells. We show here that momilactone B at micromolar doses has antitumor efficacy by inducing apoptosis in several blood cancer cells including human leukemic T cells. In addition, our study elucidated that anticancer activity of momilactone B on human leukemic T cells resulted from the induction of apoptosis via caspase and mitochondria. From these results, momilactone B can be considered as a novel therapeutic strategy for human leukemic T cells from its direct apoptosis-inducing activity.     

Lycopene supplementation suppresses oxidative stress induced by a high fat diet in gerbils

The effect of lycopene supplementation on the antioxidant system was investigated by analyzing lipid peroxide levels, glutathione contents, and antioxidant enzyme activities in Mongolian gerbils fed a high fat diet. Gerbils were fed on each experimental diet for 6 weeks; normal diet (NC), normal diet with 0.05% lycopene (NL), high fat diet (HF), and a high fat diet with 0.05% lycopene (HFL). Dietary supplementation of lycopene increased hepatic lycopene level in gerbils fed a normal or high fat diet (P < 0.05). Liver and erythrocyte concentrations of lipid peroxide increased in gerbils fed a high fat diet, whereas lycopene supplementation decreased liver and erythrocyte concentrations of lipid peroxide (P < 0.05). Hepatic total glutathione content was higher in the NL group than that in the NC group (P < 0.05). Total antioxidant status in plasma increased following lycopene supplementation compared with that of the non-lycopene supplemented groups (P < 0.05). Hepatic catalase activity increased following dietary lycopene supplementation (P < 0.05). Superoxide dismutase activity in liver remained unchanged with lycopene supplementation, but erythrocyte superoxide dismutase activity increased in NL group compared with NC group (P < 0.05). Glutathione-S-transferase activity increased in the NL group compared to NC group (P < 0.05). Liver and erythrocyte glutathione peroxidase activity increased significantly in the NL group compared to that in the HF group (P < 0.05). Liver glutathione reductase activity was higher in the NL group than that in the NC group (P < 0.05). These results suggest that lycopene supplementation may be efficient for preventing chronic diseases induced by oxidative stress related to high fat diet.