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) [ Citrus maxima (Burm.) Merr. (Rutaceae)] is reported to possess antioxidant and antimelanogenic activities. Objective To investigate the effect of PPO [ Citrus maxima (Burm.) Merr. cv. Shatian Yu ] 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 ( p < 0.05). Discussion and conclusions The neuroprotective effects of PPO in the CA rats suggested that PPO possibility as a health product enhances the resistance ability against brain injury for humans.

Pomelo Peel Essential Oil Ameliorates Cerebral Ischemia-Reperfusion Injury through Regulating Redox Homeostasis in Rats and SH-SY5Y Cells

“…We used NDS to identify the protective effect of PPEO and determine the efficacy and safety dose at 50 mg/kg. In fact, different dose of PPEO was adopted due to different research aim in our other studies in the same period [ 6 , 7 ]. Nissl staining and electron microscopy were used to observe the protective effect of PPEO from general to ultrastructural level, respectively.…”

“…However, studies report that citrus and its products have good antioxidant properties because of its high content of active substances such as terpenes, aldehydes, esters, and ketones [ 5 ]. PPEO, a crude compound extracted from pomelo peel, is considered to have potential therapeutic effects for its antioxidant properties or other biological activities [ 6 , 7 ]. In this study, we selected Shatian pomelo peculiar belonging to Rongxian, Guangxi, and extracted the essential oil from outer peel by distillation.…”

Targeting TNFα‑mediated cytotoxicity using thalidomide after experimental cardiac arrest in rats: An exploratory study

“…CA also triggers a sepsis-like inflammatory response with expression of TNFα up-regulated in cerebral ischemia. Systemic selective anti-TNFα therapies improved early recovery from CA, in both small and large animal models (4,5). Our prior studies in multiple models of CA in rats, identified a unique early cytokine response specifically in striatum, showing a dramatic >100-fold increase of TNFα vs. other brain regions including hippocampus, where no increase in TNFα was seen (6)(7)(8).…”

“…While early ischemic brain injury is the result of energy failure, neuro-inflammation could contribute, or even represent a major cause of delayed neuronal death. Tumor necrosis factor alpha (TNFα) is a pivotal cytokine that can induce neuronal apoptosis and/or necroptosis, and increase neuroinflammation (2)(3)(4).…”