PPAR-γ activator induces neuroprotection in hypercholesterolemic rats subjected to global cerebral ischemia/reperfusion injury: In vivo and in vitro inhibition of oxidative stress

Rouq, Fawzia Al; Eter, Eman El

doi:10.1016/j.exger.2013.12.008

Cited by 17 publications

(8 citation statements)

References 38 publications

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“…14,15 Similar findings have also been reported for IR studies in kidney, intestine and brain. [16][17][18][19] These studies indicate that PPAR-γ is down-regulated in IR, and agonists such as 15-deoxy-Δ 12,14 -prostaglandin J2 and rosiglitazone can alleviate IR-induced injury. Furthermore, ROS and inflammatory factors such as TNF-α, IL-6 and IL-1β can down-regulate PPAR-γ, the status of which is mainly influenced by the mitogen-activated protein kinase (MAPK) family pathway.…”

Section: Introductionmentioning

confidence: 99%

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

Xiang

Chen

et al. 2020

DDDT

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These authors contributed equally to this workObjective: Hepatic ischemia reperfusion (IR) limits the development of liver transplantation technology. The aim of this study was to explore the protective effects of Bergenin on hepatic IR, particularly the elimination of reactive oxygen species (ROS) and activation of the peroxisome proliferators activated receptor γ (PPAR-γ) pathway. Methods: Initial experiments were performed to confirm the non-toxicity of Bergenin. Mice were randomly divided into sham, IR, and IR + Bergenin (10, 20 and 40 mg/kg) groups, and serum and tissue samples were obtained at 2, 8 and 24 h for detection of liver enzymes (ALT and AST), inflammatory factors (TNF-α, IL-6 and IL-1β), ROS, cell death markers (Bcl-2, Bax, Beclin-1 and LC3) and related important pathways (PPAR-γ, P38 MAPK, NF-κB p65 and JAK2/STAT1). Results: Bergenin reduced the release of ROS, down-regulated inflammatory factors, and inhibited apoptosis and autophagy. Additionally, expression of PPAR-γ-related genes was increased and phosphorylation of P38 MAPK, NF-κB p65 and JAK2/STAT1-related proteins was decreased in Bergenin pre-treatment groups in a dose-dependent manner. Conclusion: Bergenin exerts hepatic protection by eliminating ROS, affecting the release of inflammatory factors, and influencing apoptosis-and autophagy-related genes via the PPAR-γ pathway in this model of hepatic IR injury.

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Section: Introductionmentioning

confidence: 99%

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

Xiang

Chen

et al. 2020

DDDT

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“…PPARs are transcription factors belonging to a superfamily of nuclear receptors, and three isoforms (α, δ and γ) have been described, in which PPARα and γ are known to regulate lipid metabolism and oxidative stress (28,29). Furthermore, PPARα and γ have been previously demonstrated to exert an inhibitory effect on tumor growth, muscle atrophy, and pro-inflammatory cytokine secretion and signaling in cancer cachexia (30)(31)(32)(33).…”

mentioning

confidence: 99%

L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPARγ signaling

Jiang

Zhang

et al. 2015

Molecular Medicine Reports

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The liver is crucial for systemic inflammation in cancer cachexia. Previous studies have shown that L-carnitine, as the key regulator of lipid metabolism, exerts an anti-inflammatory effect in several diseases, and ameliorates the symptoms of cachexia by regulating the expression and activity of carnitine palmitoyltransferase (CPT) in the liver. However, the effect of L-carnitine on the liver inflammatory response in cancer cachexia remains to be elucidated. The aim of the present study was to examine the role of the CPT I-dependent peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in the ameliorative effect of L-carnitine on the liver inflammatory response. This was investigated in a colon-26 tumor-bearing mouse model with cancer cachexia. Liver sections were immunohistochemically analyzed, and mRNA and protein levels of representative molecules of the CPT-associated PPARγ signaling pathway were assessed using PCR and western blot analysis, respectively. The results showed that oral administration of L-carnitine in these mice improved hepatocyte necrosis, liver cell cord derangement and hydropic or fatty degeneration of the liver cells in the liver tissues, decreased serum levels of malondialdehyde, increased serum levels of superoxide dismutase and glutathione peroxidase, and elevated the expression levels of PPARα and PPARγ at the mRNA and protein levels. These changes induced by L-carnitine were reversed by treatment with etomoxir, an inhibitor of CPT I. The inhibitory effect of L-carnitine on the increased expression level of nuclear factor (NF)-κB p65 in the peripheral blood mononuclear cells was markedly weakened by GW9662, a selective inhibitor of PPAR-γ. GW9662 also eliminated the inhibitory effect of L-carnitine on the expression of cyclooxygenase-2 (Cox-2) in the liver, and on the serum expression levels of pro-inflammatory prostaglandin E2, C-reactive protein, tumor necrosis factor-α and interleukin-6 in the cancer cachexia model mice. This reversing effect of GW9662 on L-carnitine was restored by pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB signaling. Taken together, these results demonstrated that L-carnitine ameliorated liver inflammation and serum pro-inflammatory markers in cancer cachexia through regulating CPT I-dependent PPARγ signaling, including the downstream molecules of NF-κB p65 and Cox-2.

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“…Nategh et al (2010) demonstrated that 1 mg/kg of rosiglitazone was not beneficial for brain edema in a focal ischemia rat model, whereas Hyong et al (2008) demonstrated that brain edema was not reduced by 1 or 6 mg/kg of rosiglitazone after surgical brain injury in rodents. However, 3 mg/kg of rosiglitazone, the dosage used in our study, induced a significant attenuation of cerebral edema in response to global cerebral ischemia in rats (Al Rouq and El Eter, 2014). The brain water content was reduced after rosiglitazone treatment in our study.…”

Section: Discussionmentioning

confidence: 42%

Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats

Gu¹,

Wang²,

Li³

et al. 2015

Brain Research

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PPAR-γ activator induces neuroprotection in hypercholesterolemic rats subjected to global cerebral ischemia/reperfusion injury: In vivo and in vitro inhibition of oxidative stress

Cited by 17 publications

References 38 publications

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPARγ signaling

Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats

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