Effects of Anesthesia with Pentobarbital/Ketamine on Mitochondrial Permeability Transition Pore Opening and Ischemic Brain Damage
| Autor: | Evelina Rekuviene, Laima Ivanoviene, Vilmante Borutaite, Ramune Morkuniene |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Biomedicines, Vol 12, Iss 10, p 2342 (2024) |
| Druh dokumentu: | article |
| ISSN: | 12102342 2227-9059 |
| DOI: | 10.3390/biomedicines12102342 |
| Popis: | Background and Objective: The alteration of mitochondrial functions, especially the opening of the mitochondrial permeability transition pore (mPTP), has been proposed as a key mechanism in the development of lesions in cerebral ischemia, wherefore it is considered as an important target for drugs against ischemic injury. In this study, we aimed to investigate the effects of mitochondrial complex I inhibitors as possible regulators of mPTP using an in vitro brain ischemia model of the pentobarbital/ketamine (PBK)-anesthetized rats. Results: We found that PBK anesthesia itself delayed Ca2+-induced mPTP opening and partially recovered the respiratory functions of mitochondria, isolated from rat brain cortex and cerebellum. In addition, PBK reduced cell death in rat brain slices of cerebral cortex and cerebellum. PBK inhibited the adenosine diphosphate (ADP)-stimulated respiration of isolated cortical and cerebellar mitochondria respiring with complex I-dependent substrates pyruvate and malate. Moreover, pentobarbital alone directly increased the resistance of isolated cortex mitochondria to Ca2+-induced activation of mPTP and inhibited complex I-dependent respiration and mitochondrial complex I activity. In contrast, ketamine had no direct effect on functions of isolated normal cortex and cerebellum mitochondria. Conclusions: Altogether, this suggests that modulation of mitochondrial complex I activity by pentobarbital during PBK anesthesia may increase the resistance of mitochondria to mPTP opening, which is considered the key event in brain cell necrosis during ischemia. |
| Databáze: | Directory of Open Access Journals |
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