The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke.
Bioenergetics; CDGSH; iron-sulfur; OXPHOS; PAMPA; t-MCAO
Purpose: Therapeutic strategies to treat ischemic stroke are limited due to the heterogeneity of cerebral ischemic injury and the mechanisms that contribute to the cell death. Since oxidative stress is one of the primary mechanisms that cause brain injury post-stroke, we hypothesized that therapeutic targets that modulate mitochondrial function could protect against reperfusion-injury after cerebral ischemia, with the focus here on a mitochondrial protein, mitoNEET, that modulates cellular bioenergetics.; Method: In this study, we evaluated the pharmacology of the mitoNEET ligand NL-1 in an in vivo therapeutic role for NL-1 in a C57Bl/6 murine model of ischemic stroke.; Results: NL-1 decreased hydrogen peroxide production with an IC 50 of 5.95 μM in neuronal cells (N2A). The in vivo activity of NL-1 was evaluated in a murine 1 h transient middle cerebral artery occlusion (t-MCAO) model of ischemic stroke. We found that mice treated with NL-1 (10 mg/kg, i.p.) at time of reperfusion and allowed to recover for 24 h showed a 43% reduction in infarct volume and 68% reduction in edema compared to sham-injured mice. Additionally, we found that when NL-1 was administered 15 min post-t-MCAO, the ischemia volume was reduced by 41%, and stroke-associated edema by 63%.; Conclusion: As support of our hypothesis, as expected, NL-1 failed to reduce stroke infarct in a permanent photothrombotic occlusion model of stroke. This report demonstrates the potential therapeutic benefits of using mitoNEET ligands like NL-1 as novel mitoceuticals for treating reperfusion-injury with cerebral stroke.
Saralkar P; Mdzinarishvili A; Arsiwala TA; Lee Y; Sullivan PG; Pinti MV; Hollander JM; Kelley EE; Ren X; Hu H; Simpkins J; Brown C; Hazlehurst LE; Huber JD; Geldenhuys WJ
Pharmaceutical Research
2021
2021-05-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1007/s11095-021-03046-4" target="_blank" rel="noreferrer noopener">10.1007/s11095-021-03046-4</a>
Suppression of the inflammatory cascade is implicated in resveratrol chemoprevention of experimental hepatocarcinogenesis.
Animals; Anticarcinogenic Agents/*therapeutic use; Chemoprevention; Cyclooxygenase 2/immunology; Diethylnitrosamine; Female; HSP70 Heat-Shock Proteins/immunology; Humans; Inflammation/prevention & control; Liver Neoplasms/chemically induced/*immunology/*prevention & control; Liver/drug effects/pathology; NF-kappa B/immunology; Rats; Resveratrol; Sprague-Dawley; Stilbenes/*therapeutic use
PURPOSE: Resveratrol, present in grapes and red wine, has been found to prevent diethylnitrosamine (DENA)-initiated rat liver tumorigenesis, though the chemopreventive mechanisms are not completely elucidated. The current study was designed to explore whether the antiinflammatory properties of resveratrol play a role in its antihepatocarcinogenic action. METHODS: Liver samples were harvested from a 20-week chemopreventive study in which resveratrol (50, 100 and 300 mg/kg) was shown to inhibit DENA-induced hepatocyte nodules in Sprague-Dawley rats in a dose-responsive manner. Hepatic preneoplastic and inflammatory markers, namely heat shock protein (HSP70), cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB), were studied using immunohistochemical as well as Western blot techniques. RESULTS: Resveratrol dose-dependently suppressed DENA-induced increased expressions of hepatic HSP70 and COX-2. Resveratrol also attenuated the
Bishayee Anupam; Waghray Abhijeet; Barnes Kendra F; Mbimba Thomas; Bhatia Deepak; Chatterjee Malay; Darvesh Altaf S
Pharmaceutical research
2010
2010-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s11095-010-0144-4" target="_blank" rel="noreferrer noopener">10.1007/s11095-010-0144-4</a>