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Pomelo peel oil suppresses TNF-α-induced necroptosis and cerebral ischaemia-reperfusion injury in a rat model of cardiac arrest.

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PMID:  Pharm Biol. 2021 Dec ;59(1):401-409. PMID: 33794116 Abstract Title:  Pomelo peel oil suppresses TNF-α-induced necroptosis and cerebral ischaemia-reperfusion injury in a rat model of cardiac arrest. Abstract:  CONTEXT: Pomelo peel oil (PPO) [(Burm.) Merr. (Rutaceae)] is reported to possess antioxidant and antimelanogenic activities.OBJECTIVE: To investigate the effect of PPO [(Burm.) Merr.] on tumour necrosis factor-α (TNF-α)-induced necroptosis in cerebral ischaemia-reperfusion injury (CIRI) after cardiac arrest (CA).MATERIALS AND METHODS: Male Sprague Dawley rats were randomly assigned to six groups: sham group, PP0-L (10 mg/kg), PPO-M (20 mg/kg), PPO-H (40 mg/kg) and two control groups (CA, 0.9% saline; Gly, 10% glycerol). All drugs were administered intravenously to the CA/CPR rats within 10 min after return of spontaneous circulation (ROSC). After 24 h, rats were assessed for neuronal injury via the neurological deficit score (NDS), cerebral cortex staining and transmission electron microscopy (TEM) and expression levels of TNF-α and necroptosis-related proteins by immunoreactivity staining and western blotting.RESULTS: Compared to those in the sham group (survival rate, 100% and NDS, 80), the survival rate and NDS were significantly reduced in the model groups (CA, 56.25%, 70; Gly, 62.5%, 71; PPO-L, 75%, 72; PPO-M, 87.5%, 75; PPO-H, 81.25%, 74). In the PPO-M group, Nissl bodies were significantly increased (43.67 ± 1.906 vs. 17 ± 1.732), the incidence of pathomorphological injury was lower and the necroptosis markers (TNF-α, RIPK1, RIPK3, p-MLKL/MLKL) expression was downregulated compared to those in the CA group ( 

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