benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and deoxynivalenol

DON is commonly found in foods and feeds; it presents health risks, especially an increase of growth inhibition in humans, particularly infants and young children. However, there are relatively few research studies devoted to the mechanism of DON-mediated growth retardation. Interestingly, our results showed that DON does not cause any significant production of ROS but results in a persistent and significant release of NO with iNOS increasing activity, mitochondrial ultrastructural changes and decreasing ΔΨm. Moreover, the significant decreases in GH production and secretion induced by DON were dose-dependent, accompanied by an increase of caspase 3, 8 and 9, IL-11, IL-lβ and GHRH. NO scavenging agent (haemoglobin) and free radical scavenging agent (N-acetylcysteine) partially reversed mitochondrial damage, and Z-VAD-FMK increased the levels of GH and decreased the levels of caspase 3, 8 and 9, while haemoglobin decreased the levels of caspase 3, 8 and 9, indicating that NO is the primary target of DON-mediated inhibition. Present research study firstly demonstrated that NO is a key mediator of DON-induced growth inhibition and plays critical roles in the interference of GH transcription and synthesis. The current research is conducive to future research on the molecular mechanisms of DON-induced growth inhibition in humans, especially children.

Topics: Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Caspases; Cell Line, Tumor; Child; Child, Preschool; Environmental Exposure; Food Contamination; Growth Disorders; Growth Hormone; Growth Hormone-Releasing Hormone; Hemoglobins; Humans; Infant; Interleukins; Mitochondria; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Rats; Reactive Oxygen Species; Signal Transduction; Trichothecenes