Rutin hydrate inhibits apoptosis in the brains of cadmium chloride-treated rats via preserving the mitochondrial integrity and inhibiting endoplasmic reticulum stress

Mostafa, Dalia G.; Khaleel, Eman F.; Badi, Rehab M.; Abdel-Aleem, Ghada A.; Abdeen, Hanaa M.

doi:10.1080/01616412.2019.1596206

Cited by 29 publications

(25 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, the timing of these events strongly suggested that ROS could be the initiator of the ER stress. Furthermore, transient up-regulation of the GRP78 protein, here observed upon 16 h of Cd treatment, is in agreement with the cytoprotective role of this chaperone [97,98], supporting the role of ER stress in trying to maintain cell homeostasis [54,55,56].…”

Section: Discussionsupporting

confidence: 77%

“…Furthermore, it is worth noting that a large volume of data points out that the neurotoxic effects of Cd ions are mainly mediated by the indirect production of high levels of reactive oxygen species (ROS) and induction of apoptosis [52,53]. On the other hand, the contribution of the endoplasmic reticulum (ER) stress response to oxidative stress in maintaining cell homeostasis and eventually triggering apoptosis signaling, as well as in playing a key role in Cd-induced mitochondrial-mediated apoptosis, has been recently demonstrated in different in vitro and in vivo studies [54,55,56].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier

Branca

Maresca

Morucci

et al. 2019

IJMS

View full text Add to dashboard Cite

Cadmium (Cd) is a highly toxic environmental pollutant released from the smelting and refining of metals and cigarette smoking. Oral exposure to cadmium may result in adverse effects on a number of tissues, including the central nervous system (CNS). In fact, its toxicity has been related to neurological disorders, as well as neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Under normal conditions, Cd barely reaches the brain in adults because of the presence of the blood–brain barrier (BBB); however, it has been demonstrated that Cd-dependent BBB alteration contributes to pathogenesis of neurodegeneration. However, the mechanism underlying Cd-dependent BBB alteration remain obscure. Here, we investigated the signaling pathway of Cd-induced tight junction (TJ), F-actin, and vimentin protein disassembly in a rat brain endothelial cell line (RBE4). RBE4 cells treated with 10 μM cadmium chloride (CdCl2) showed a dose- and time-dependent significant increase in reactive oxygen species (ROS) production. This phenomenon was coincident with the alteration of the TJ zonula occludens-1 (ZO-1), F-actin, and vimentin proteins. The Cd-dependent ROS increase elicited the upregulation of GRP78 expression levels, a chaperone involved in endoplasmic reticulum (ER) stress that induces caspase-3 activation. Further signal profiling by the pannexin-1 (PANX1) specific inhibitor 10Panx revealed a PANX1-independent increase in ATP spillage in Cd-treated endothelial cells. Our results point out that a ROS-dependent ER stress-mediated signaling pathway involving caspase-3 activation and ATP release is behind the BBB morphological alterations induced by Cd.

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier

Branca

Maresca

Morucci

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…23,30 It was also revealed that cadmium can induce the mitochondrial apoptotic pathway via up-regulation of JNK and p38 MAPKs resulting in increased Bax/Bcl-2 ratio, and caspase-3 activity. 25,31 This is similar to the current work, which showed that cadmium exposure increased p-JNK and p38 MAPKs, NF-κB p65, Bax/Bcl-2 ratio and caspase-3 and in rat pancreas. Besides, previous investigations, similar to the present one, showed that NGN and VLN provided their anti-inflammatory and anti-apoptotic effects via down-regulation of JNK and p38 MAPKs signaling pathways with subsequent reduction of inflammatory cytokines, Bax/Bcl-2 ratio and caspase-3.…”

Section: Discussionsupporting

confidence: 90%

“…Subsequently, activation of caspase family of proteases takes place and activated caspased-3 eventually executes apoptotic cell death. 24,25 Both NGN (4ˊ,5,7-trihydroxy flavanone), and VLN (4-hydroxy-3-methoxybenzaldehyde) are natural compounds with prominent antioxidant, anti-inflammatory and anti-apoptotic effects. It was reported in the literature that NGN and VLN significantly protected against oxidative stress and inflammatory injuries of various organs, including the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Naringenin and Vanillin Mitigate Cadmium-Induced Pancreatic Injury in Rats via Inhibition of JNK and p38 MAPK Pathways

Fouad¹,

Amin²,

Ahmed³

2020

View full text Add to dashboard Cite

Chemicals NGN, VLN and CdCl 2 were purchased from Sigma-Aldrich, USA. VLN and CdCl 2 were ABSTRACT Background: Cadmium can induce pancreatic injury via oxidative stress, inflammation and apoptosis. Naringenin (NGN) and vanillin (VLN) exert antioxidant, anti-inflammatory, and antiapoptotic effects. Objective: The likely ameliorative effects of NGN, VLN and their combination were studied in rats exposed to cadmium-induced pancreatic injury. Materials and Methods: Rats received NGN (50 mg/kg/day, p.o.), VLN (100 mg/ kg/day, p.o.), or NGN + VLN for 7 days and one injection of CdCl 2 (2 mg/kg, i.p.) on the 6 th day. Results: Cadmium significantly lowered serum amylase and insulin levels. Cadmium also caused significant increments of malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65, Bax/Bcl-2 ratio and phosphorylated c-Jun N-terminal kinase (p-JNK) and p38 mitogen-activated protein kinases (MAPKs) and significant decrements of reduced glutathione and catalase in the pancreas of rats received CdCl 2. Additionally, CdCl 2 caused marked histopathological necrosis and significantly increased caspase-3 expression in pancreatic tissue. The cadmium-induced biochemical, histopathological and immunohistochemical changes were significantly ameliorated by NGN, VLN and NGN + VLN. However, NGN + VLN caused more significant ameliorative effects than did NGN and VLN alone. Conclusion: NGN, VLN and NGN + VLN afforded significant protection of pancreas in rats exposed to cadmium insult through modulation of JNK and p38 MAPK pathways and inhibition of oxidative stress, inflammation and apoptosis.

show abstract

“…22,23 Rutin inhibits apoptosis through preserving mitochondrial integrity in the brain of CdCl 2 -treated rats and mice with traumatic brain injury. 40,41 Mitochondrial apoptosis The generation of intracellular ROS triggers the activation of the mitochondrial apoptotic pathway. 43 In H 2 O 2 -treated human umbilical vein endothelial cells, pretreatment rutin attenuates excessive ROS generation.…”

Section: Effects Of Rutin On Bisgma-inhibited Aoe Activities In Rawmentioning

confidence: 99%

Rutin‐protected BisGMA‐induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes

Huang

Chang

et al. 2020

Environmental Toxicology

View full text Add to dashboard Cite

Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and-9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with Yin-Che Lu and Yu-Hsiang Kuan contributed equally to this work.

show abstract

Rutin hydrate inhibits apoptosis in the brains of cadmium chloride-treated rats via preserving the mitochondrial integrity and inhibiting endoplasmic reticulum stress

Cited by 29 publications

References 48 publications

Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier

Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier

Naringenin and Vanillin Mitigate Cadmium-Induced Pancreatic Injury in Rats via Inhibition of JNK and p38 MAPK Pathways

Rutin‐protected BisGMA‐induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes

Contact Info

Product

Resources

About