Protective Effect of Quercetin against Oxidative Stress and Brain Edema in an Experimental Rat Model of Subarachnoid Hemorrhage

Dong, Yushu; Wang, Ju-lei; Feng, Dayun; Qin, Huaizhou; Hua, Wen; Yin, Zhongmin; Gao, Guodong; Li, Chuan

doi:10.7150/ijms.7634

Cited by 114 publications

(82 citation statements)

References 51 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…i.e., it has been reported that Caspase-3 expression was amplified in cortical neurons after brain ischemic injuries and inhibition of Caspase-3 reduces the neuronal loss and brain edema [20,21]. Our recent study also demonstrated that Caspase-3 is upregulated in in the rat hippocampus after CA [16].…”

Section: Introductionmentioning

confidence: 55%

“…Caspase-3 is a predominant target involved in the reactive oxygen species-mediated ischemia induced apoptosis in neuronal cells, and neuronal apoptosis results in blood brain barrier dysfunction, inflammation and oxidative cascades and thereby leading to brain damage [25,26]. It has been reported that Caspase-3 expression was exaggerated in cortical neurons after brain ischemic injuries and inhibition of Caspase-3 reduces the neuronal loss and brain edema [20,26]. In addition, a greater number of neurons that are stained with terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) are found in hippocampus as apoptosis is engaged in the pathological process of global ischemia-induced neuronal loss due to CA [14].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

Xing

2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1α) in regulating pro-inflammatory cytokines (PICs) pathway in the rat hippocampus after cardiac arrest (CA) induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR). Those PICs include interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1α and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1β, IL-6 and TNF-α were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1α and the time courses for HIF-1α and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1α by systemic administration of ML228, HIF-1α activator, significantly attenuated the amplified IL-6/IL-6R and TNF-α /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1β and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1β, IL-6 and TNF-α and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1α plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1α improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that HIF-1α plays an important role in regulating PIC signal pathways and Caspase-3. The subsequent induction of HIF-1α and its target signals is likely a part of the intrinsic neuroprotective effects aimed at attenuating damage as a result of global cerebral ischemia. Thus, targeting one or more of these signaling molecules has clinical implications for treatment and improvement of CA-evoked global cerebral ischemia often observed in clinics.

show abstract

Section: Introductionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

Xing

2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…We used 18 male albino Wistar rats, about 2 months old, weighing 200-220 g to exclude possible protective effects of oestradiol against provoked oxidative stress (15,16 (4,(17)(18)(19)(20)(21) and correspond to the human daily dietary intake of quercetin and vitamin C enriched food and the daily nicotine intake in people who smoke 10-20 cigarettes per day (2,4).…”

Section: Experimental Designmentioning

confidence: 99%

Protective effects of quercetin and vitamin C against nicotine-induced toxicity in the blood of Wistar rats

Paunović

Ognjanović

Matić

et al. 2016

Archives of Industrial Hygiene and Toxicology

View full text Add to dashboard Cite

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. The aim of our study was to investigate the prooxidative effects of nicotine and protective (additive or synergistic) effects of quercetin and vitamin C in the blood of experimental animals, to determine whether the combination of these antioxidants might be beneficial for clinical purposes. Wistar albino rats were receiving intraperitoneal nicotine injection (0.75 mg kg -1 per day) or saline (control group) or nicotine plus quercetin (40 mg kg -1 per day) and vitamin C (100 mg kg -1 per day) for three consecutive days. On day 4, we determined their blood lipid profile, liver enzymes, oxidative stress parameters, and antioxidative system parameters. Compared to untreated control, nicotine significantly increased total cholesterol, LDLcholesterol, triglycerides, liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) and oxidative stress parameters (superoxide anion, hydrogen peroxide, and lipid peroxide) and decreased HDL-cholesterol, glutathione, and superoxide dismutase/catalase activity. Quercetin + vitamin C reversed these values significantly compared to the nicotine alone group. Our results confirm that nicotine has significant prooxidative effects that may disrupt the redox balance and show that the quercetin + vitamin C combination supports antioxidant defence mechanisms with strong haematoprotective activity against nicotine-induced toxicity. In practical terms, this means that a diet rich in vitamin C and quercetin could prevent nicotine-induced toxicity and could also be useful in the supportive care of people exposed to nicotine.

show abstract

“…Neuronal apoptosis result in blood brain barrier dysfunction, inflammation and oxidative cascades and thereby leading to brain damage [23,24]. It has been reported that Caspase-3 expression was exaggerated in cortical neurons after subarachnoid hemorrhage and inhibition of Caspase-3 reduces the neuron loss and brain edema [24,25]. Our current study showed that activated Caspase-3 by ICH was significantly attenuated by ICV infusion of ML288 stabilizing HIF-1α levels after induction of ICH.…”

Section: Discussionmentioning

confidence: 48%

Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes

Tang

Chen

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.Copyright © 2015 S. Karger AG, Basel Key Words Intracerebral hemorrhage • HIF-1α • VEGF • DiabetesAbstract Background/Aims: HIF-1α is accumulated in the cellular nucleus and cytoplasm under conditions of oxygen deprivation and engaged in pathophysiologic changes of homeostasis by modulating the expression of several target genes. As an endogenous signaling protein, HIF-1α contributes to in neuroprotection, erythropoiesis, and apoptosis modulation. The purpose of this study was to examine the role played by HIF-1α in regulating neurological injury evoked by intracerebral hemorrhage (ICH) through its downstream product, namely vascular endothelial growth factor (VEGF). In particular, we examined the effects of diabetic hyperglycemia on HIF-1α response in the processing of ICH. Methods: ELISA was used to measure HIF-1α and VEGF; and Western Blot analysis to examine the protein expression of VEGFR-2 and Caspase-3. Neurological Severity Score and brain water content were used to indicate neurological function and brain edema. Results: HIF-1α and VEGF were significantly increased in the brain after induction of ICH in non-diabetic control rats and diabetic rats; however, the amplified levels of HIF-1α and VEGF were attenuated in diabetic rats (P<0.05 vs. non-diabetic rats) as compared with non-diabetic rats. Also, the protein expression of VEGF receptor subtype 2 was significantly less in the brain of diabetic rats (P<0.05 vs. nondiabetic rats). Further, cerebral infusion of HIF-1 activator stabilized VEGF levels, attenuated Caspase-3 and improved neurological deficits induced by ICH and the effects are smaller in diabetic animals. Conclusion: HIF-1α activated by ICH likely plays a beneficial role via VEGF mechanisms and response of HIF-1α is largely impaired in diabetes. This has pharmacological implications to target specific HIF-1α and VEGF pathway for neuronal dysfunction and vulnerability related to ICH.

show abstract

Protective Effect of Quercetin against Oxidative Stress and Brain Edema in an Experimental Rat Model of Subarachnoid Hemorrhage

Cited by 114 publications

References 51 publications

HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

Protective effects of quercetin and vitamin C against nicotine-induced toxicity in the blood of Wistar rats

Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes

Contact Info

Product

Resources

About