sirolimus and trimethyloxamine

Plant-based diets are becoming more popular for many reasons, and epidemiological as well as clinical data also suggest that a well-balanced vegan diet can be adopted for the prevention, and in some cases, in the treatment of many diseases. In this narrative review, we provide an overview of the relationships between these diets and various conditions and their potential biochemical background. As whole plant foods are very rich in food-derived antioxidants and other phytochemicals, they have many positive physiological effects on different aspects of health. In the background of the beneficial health effects, several biochemical processes could stand, including the reduced formation of trimethylamine oxide (TMAO) or decreased serum insulin-like growth factor 1 (IGF-1) levels and altered signaling pathways such as mechanistic target of rapamycin (mTOR). In addition, the composition of plant-based diets may play a role in preventing lipotoxicity, avoiding N-glycolylneuraminic acid (Neu5Gc), and reducing foodborne endotoxin intake. In this article, we attempt to draw attention to the growing knowledge about these diets and provide starting points for further research.

Topics: Animals; Antioxidants; Biochemical Phenomena; Diet; Diet, Vegan; Endotoxemia; Humans; Insulin-Like Growth Factor I; Methylamines; Neoplasms; Sirolimus; TOR Serine-Threonine Kinases; Vegans

Metabonomics is the latest "omics" science and provides metabolic endpoints of drug toxicity, drug efficacy, and pathophysiology. With high-resolution 'H-NMR (nuclear magnetic resonance)spectroscopy on body fluids (eg, urine, blood samples) used in combination with statistical tools, metabolic biomarkers of drug toxicity can be distinguished and validated. For 2 decades, immuno-suppressant cyclosporine (CsA) has been used in transplantation medicine as a potent calcineurin inhibitor with well-known nephrotoxic side effects. The combination of CsA with novel macrolide immunosuppressants-sirolimus (SRL) or everolimus (RAD)-has proved to have a beneficial synergistic immunosuppressive effect but may also possess an increased nephrotoxic potential. 1H-NMR spectroscopy was performed on the blood from CsA-, SRL-, and RAD (alone and in combination)-treated rats to predict metabolic toxicity and to identify and quantify specific metabolic biomarkers. After 6 days of treatment with 10 mg/kg CsA, a significant increase in blood glucose, hydroxybutyrate, creatine+creatinine, trimethylamine-N-oxide (TMAO), and cholesterol as well as a decrease in total glutathione concentrations were observed. SRL (3 mg/kg) enhanced the magnitude of CsA metabolic changes (enhanced toxicity),whereas combination with RAD (3 mg/kg) partly curtailed them. Together with pharmacokinetic studies, quantitative NMR-based metabonomics represents a powerful tool for pharmacokinetic-pharmacodynamic-toxicodynamic evaluation in drug research.

Topics: Animals; Biomarkers; Blood Glucose; Cholesterol; Creatine; Creatinine; Cyclosporine; Deuterium; Drug Interactions; Drug Monitoring; Everolimus; Glutathione; Hydroxybutyrates; Immunosuppressive Agents; Lactates; Magnetic Resonance Spectroscopy; Methylamines; Rats; Reproducibility of Results; Sirolimus; Time Factors