10-nitro-oleic-acid and Obesity

10-nitro-9(E)-octadec-9-enoic acid (CXA-10), a novel nitro fatty acid compound, demonstrates potential as a therapeutic agent in multiple disease indications in which oxidative stress, inflammation, fibrosis, and/or direct tissue toxicity play significant roles. Phase I studies were conducted in healthy and obese subjects to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of oral CXA-10 after single and multiple doses in the fed and fasted states that would confirm the mechanisms of action of CXA-10. After single and multiple ascending doses, CXA-10 demonstrated dose-proportional increases in plasma exposure. CXA-10 decreased levels of biomarkers associated with altered inflammation and metabolic stress observed from nonclinical studies. In CXA-10-202, a consistent decrease from baseline was observed with CXA-10 150 mg dose, but not 25 or 450 mg doses, for biomarkers of altered inflammation and metabolic dysfunction, including leptin, triglycerides, cholesterol, MCP-1, and IL-6. In CXA-10-203, after coadministration with CXA-10, geometric mean peak plasma concentration (C

Topics: Abdominal Pain; Administration, Oral; Adult; Area Under Curve; Biomarkers; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fasting; Female; Healthy Volunteers; Humans; Incidence; Inflammation; Lipid Metabolism; Male; Middle Aged; Nausea; Nitro Compounds; Obesity; Oleic Acids; Postprandial Period; Young Adult

Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO

Topics: Adolescent; Adult; Animals; Anti-Asthmatic Agents; Antigens, Dermatophagoides; Asthma; Bile Acids and Salts; Diet, High-Fat; Drug Evaluation, Preclinical; Fatty Acids; Female; Forced Expiratory Volume; Glycocholic Acid; Humans; Liver; Lung; Male; Mice; Mice, Inbred C57BL; Middle Aged; Nitro Compounds; Obesity; Oleic Acids; Respiratory Hypersensitivity; Thinness; Ursodeoxycholic Acid; Vital Capacity; Young Adult