4-Hydroxynonenal [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
====== 4-Hydroxynonenal ======

[[Ischemia reperfusion injury]] produce [[reactive oxygen species]] that promote the [[Lipid peroxidation]]
process resulting in the production of an endogenic [[lipid peroxide]], 4-hydroxy-trans-2-nonenal (4-HNE), a highly cytotoxic aldehyde that induces cell death.

[[4-Hydroxynonenal]], or 4-hydroxy-2-nonenal or 4-HNE or HNE, (C9H16O2), is an α,β-unsaturated hydroxyalkenal that is produced by lipid peroxidation in cells. 4-HNE is the primary alpha,beta-unsaturated hydroxyalkenal formed in this process.
----
Noguchi et al. from [[Fukuoka]], synthesized a novel 4-HNE [[scavenger]] - a [[carnosine]]-[[hydrazide]] derivative, l-carnosine hydrazide (CNN) - and examined its [[neuroprotection]] effect in a model of transient [[ischemia]]. [[PC12 ]]cells were pre-incubated with various doses (0-50 mmol/L) of CNN for 30 min, followed by incubation with 4-HNE (250 μM). An MTT assay was performed 24 h later to examine cell survival. Transient ischemia was induced by bilateral [[common carotid artery]] [[occlusion]] (BCCO) in the Mongolian gerbil. Animals were assigned to sham-operated (n = 6), placebo-treated (n = 12), CNN pre-treated (20 mg/kg; n = 12), CNN post-treated (100 mg/kg; n = 11), and histidyl hydrazide (a previously known 4-HNE scavenger) post-treated (100 mg/kg; n = 7) groups. [[Heat shock protein]] 70 immunoreactivity in the hippocampal [[CA1]] region was evaluated 24 h later, while delayed [[neuronal death]] using 4-HNE staining was evaluated 7 days later. Pre-incubation with 30 mmol/L CNN completely inhibited 4-HNE-induced cell toxicity. CNN prevented delayed neuronal death by >60% in the pre-treated group (p < 0.001) and by >40% in the post-treated group (p < 0.01). Histidyl hydrazide post-treatment elicited no protective effect. CNN pre-treatment resulted in high heat shock protein 70 and low 4-HNE immunoreactivity in CA1 pyramidal neurons. Higher 4-HNE immunoreactivity was also found in the placebo-treated animals than in the CNN pre-treated animals. Our novel compound, CNN, elicited highly effective 4-HNE scavenging activity in vitro. Furthermore, CNN administration both pre- and post-BCCO remarkably reduced delayed neuronal death in the hippocampal CA1 region via its induction of heat shock protein 70 and scavenging of 4-HNE
((Noguchi K, Ali TFS, Miyoshi J, Orito K, Negoto T, Biswas T, Taira N, Koga R,
Okamoto Y, Fujita M, Otsuka M, Morioka M. Neuroprotective effects of a novel
carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral
ischemia. Eur J Med Chem. 2018 Nov 28;163:207-214. doi:
10.1016/j.ejmech.2018.11.060. [Epub ahead of print] PubMed PMID: 30522055.
)).