Chrysin attenuates global cerebral ischemic reperfusion injury via suppression of oxidative stress, inflammation and apoptosis

Khashab, Iman H. El; Abdelsalam, Rania M.; El-Brairy, Amany I.; Attia, Amina S.

doi:10.1016/j.biopha.2019.108619

Cited by 45 publications

(35 citation statements)

References 60 publications

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“…Previous studies have demonstrated that Hsp90 was involved in apoptosis as well as inflammation in cardiac muscle and neuron cells 29,30 . Recent studies demonstrated that inhibition of Hsp90 by the 17-allylamino-17-demethoxygeldanamycin (17-AAG) or 17-DMAG attenuated UUO, indoxyl sulfate (IS), and high salt-diet-induced renal fibrosis 20,24,31 .…”

Section: Discussionmentioning

confidence: 99%

DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

Pan

et al. 2020

Nat Commun

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Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.

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Section: Discussionmentioning

confidence: 99%

DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

Pan

et al. 2020

Nat Commun

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“…The prevention and treatment of CIRI have gained increased attention in the field of global IR research (24,25). Blocking neuronal apoptosis is the most important step in alleviating CIRI (26). Apoptosis is a major mode of neuron death following CIRI, particular apoptosis induced by the ERS pathway (8).…”

Section: Discussionmentioning

confidence: 99%

Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis

Kong

Cheng

et al. 2021

Mol Med Rep

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Orexin-A (OXA) protects neurons against cerebral ischemia-reperfusion injury (CIRI). Endoplasmic reticulum stress (ERS) induces apoptosis after CIRI by activating caspase-12 and the CHOP pathway. The present study aimed to determine whether OXA mitigates CIRI by inhibiting ERS-induced neuronal apoptosis. A model of CIRI was established, in which rats were subjected to middle cerebral artery occlusion with ischemic intervention for 2 h, followed by reperfusion for 24 h. Neurological deficit examination and 2,3,5-triphenyltetrazolium chloride staining were performed to assess the level of CIRI and neuroprotection by OXA. Expression levels of ERS-related proteins and cleaved caspase-3 were measured via western blotting, while the rate of neuronal apoptosis in the cortex was determined using a TUNEL assay. OXA treatment decreased the infarct volume of rats after CIRI and attenuated neuron apoptosis. Furthermore, administration of OXA decreased the expression levels of GRP78, phosphorylated (p)-PERK, p-eukaryotic initiation factor-2α, p-inositol requiring enzyme 1α, p-JNK, cleaved caspase-12, CHOP and cleaved caspase-3, all of which were induced by CIRI. Collectively, these findings suggested that OXA attenuated CIRI by inhibiting ERS-mediated apoptosis, thus clarifying the mechanism underlying its neuroprotective effect and providing a novel therapeutic direction for the treatment of CIRI.

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“…erebral ischemia/reperfusion (I/R) injury is one of the major causes of neurological deterioration, mortality, and disability worldwide (El Khashab, Abdelsalam, Elbrairy, & Attia, 2019;Khoshnam, Sarkaki, Rashno, & Farbood, 2018;Yao et al, 2014;Zhang Yan, Li, & Yang, 2017). This injury is distinguished by a transient diminution of localized blood flow to brain tissue due to either arterial occlusion or systemic hypoperfusion (Khoshnam, Winlow, Farzaneh, Farbood, & Moghaddam, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…This injury is distinguished by a transient diminution of localized blood flow to brain tissue due to either arterial occlusion or systemic hypoperfusion (Khoshnam, Winlow, Farzaneh, Farbood, & Moghaddam, 2017). Various biomechanisms participate in the pathology of cerebral ischemia/reperfusion injury, such as excitotoxicity, inflammation, oxidative stress, and apoptotic cell death (El Khashab et al, 2019). Hippocampus, one of the most sensitive regions regard to ischemia, is the cortical structure that controls behaviors looking like cognition, locomotion, exploratory activity, and anxiety.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Chrysin Mediated by Estrogenic Receptors Following Cerebral Ischemia and Reperfusion in Male Rats

Shooshtari

Farbood

Mansouri

et al. 2021

BCN

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Introduction: Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. Neuroprotective strategies were reported to attenuate cognitive deficits after ischemic incidents. Here we studied the neuroprotective potential of chrysin in a rat model of cerebral Ischemia/Reperfusion (I/R) in the presence or absence of Estrogen Receptors (ERs). Methods: Adult male Wistar rats were pretreated with chrysin (CH) (CH; 30 mg/kg; gavage; for 21 consecutive days) alone or with selective ERs antagonists (ERα antagonist MPP; ERβ antagonist PHTPP; IP) or nonselective ERs antagonist (ICI182780; IP). Then, the bilateral common carotid arteries were occluded for 20 min, which was followed by 72 h reperfusion. Subsequently, cognitive performance was evaluated by Morris Water Maze (MWM) and shuttle box tasks, and afterward, their hippocampi were removed for ELISA assays and H&E staining. Oxidative indicators Malondialdehyde (MDA) and Glutathione Peroxidase (GPx), as well as inflammation mediators interleukin (IL)-1β and tumor necrosis factor-alpha (TNFα), were measured using commercial kits. Results: Results of the current study showed that the anti-oxidative and anti-inflammatory properties of CH are possible mechanisms that could improve cognitive deficits and prevent neuronal cell death following I/R (P<0.001). These effects were reversed by ICI182780 (P>0.05). Furthermore, when chrysin was co-treated with ERβ antagonist, PHTPP showed a weak neuroprotective effect in I/R rats. However, these parameters were not significantly different when chrysin was combined with ERα antagonist MPP. Conclusion: Our data confirm that chrysin could potentially serve as a neuroprotective agent against devastating effects of cerebral I/R injury, which may be mediated via its interaction with ERs, especially ERβ.

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Chrysin attenuates global cerebral ischemic reperfusion injury via suppression of oxidative stress, inflammation and apoptosis

Cited by 45 publications

References 60 publications

DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis

Neuroprotective Effects of Chrysin Mediated by Estrogenic Receptors Following Cerebral Ischemia and Reperfusion in Male Rats

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