Neuroprotective Effects of Tryptanthrin-6-Oxime in a Rat Model of Transient Focal Cerebral Ischemia.

Autor: Plotnikov MB; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia.; Faculty of Radiophysics, National Research Tomsk State University, Tomsk 634050, Russia., Chernysheva GA; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia., Smol'yakova VI; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia., Aliev OI; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia., Anishchenko AM; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia.; Department of Pharmacology, Siberian State Medical University, Tomsk 634050, Russia., Ulyakhina OA; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia., Trofimova ES; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia.; Department of Pharmacology, Siberian State Medical University, Tomsk 634050, Russia., Ligacheva AA; Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634028, Russia., Anfinogenova ND; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634012, Russia., Osipenko AN; Department of Pharmacology, Siberian State Medical University, Tomsk 634050, Russia., Kovrizhina AR; Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia., Khlebnikov AI; Kizhner Research Center, Tomsk Polytechnic University, Tomsk 634050, Russia., Schepetkin IA; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA., Drozd AG; Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk 634050, Russia., Plotnikov EV; Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk 634050, Russia.; Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk 634014, Russia., Atochin DN; Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02115, USA., Quinn MT; Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Jul 25; Vol. 16 (8). Date of Electronic Publication: 2023 Jul 25.
DOI: 10.3390/ph16081057
Abstrakt: The activation of c -Jun N-terminal kinase (JNK) plays an important role in stroke outcomes. Tryptanthrin-6-oxime (TRYP-Ox) is reported to have high affinity for JNK and anti-inflammatory activity and may be of interest as a promising neuroprotective agent. The aim of this study was to investigate the neuroprotective effects of TRYP-Ox in a rat model of transient focal cerebral ischemia (FCI), which involved intraluminal occlusion of the left middle cerebral artery (MCA) for 1 h. Animals in the experimental group were administered intraperitoneal injections of TRYP-Ox 30 min before reperfusion and 23 and 47 h after FCI. Neurological status was assessed 4, 24, and 48 h following FCI onset. Treatment with 5 and 10 mg/kg of TRYP-Ox decreased mean scores of neurological deficits by 35-49 and 46-67% at 24 and 48 h, respectively. At these doses, TRYP-Ox decreased the infarction size by 28-31% at 48 h after FCI. TRYP-Ox (10 mg/kg) reduced the content of interleukin (IL) 1β and tumor necrosis factor (TNF) in the ischemic core area of the MCA region by 33% and 38%, respectively, and attenuated cerebral edema by 11% in the left hemisphere, which was affected by infarction, and by 6% in the right, contralateral hemisphere 24 h after FCI. TRYP-Ox reduced c -Jun phosphorylation in the MCA pool at 1 h after reperfusion. TRYP-Ox was predicted to have high blood-brain barrier permeability using various calculated descriptors and binary classification trees. Indeed, reactive oxidant production was significantly lower in the brain homogenates from rats treated with TRYP-Ox versus that in control animals. Our data suggest that the neuroprotective activity of TRYP-Ox may be due to the ability of this compound to inhibit JNK and exhibit anti-inflammatory and antioxidant activity. Thus, TRYP-Ox may be considered a promising neuroprotective agent that potentially could be used for the development of new treatment strategies in cerebral ischemia.
Databáze: MEDLINE
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