Inflammatory Response Modulation through a PPARγ Agonist during Surgically Induced Visceral Ischemia in an Animal Model

Pane, Bianca; Gazzola, Valerio; Spinella, Giovanni; Bagnato, Paola; Grillo, Federica; Vellone, Valerio Gaetano; Palombo, Domenico

doi:10.1016/j.avsg.2017.09.019

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…It has been shown that pioglitazone could improve diabetic kidney diseases by inhibiting insulin resistance or oxidative stress (Ali et al, 2016). Previous studies also showed that pioglitazone exhibits a protective effect against IRI via its anti-apoptotic, anti-inflammatory, and antioxidant activities (Reel et al, 2013;Ali et al, 2018;Pane et al, 2018). In this study, we created a model of renal IRI by cultivating RTECs with H/R injury under HG conditions.…”

Section: Discussionmentioning

confidence: 94%

Pioglitazone Attenuates Reoxygenation Injury in Renal Tubular NRK-52E Cells Exposed to High Glucose via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Zou

Zhou

et al. 2020

Front. Pharmacol.

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Renal ischemia-reperfusion injury is a major cause of acute kidney injury. In the present study, we investigated the effects of pioglitazone on hypoxia/reoxygenation (H/R) injury in rat renal tubular epithelial cells (RTECs) under normal-(NG) or high-glucose (HG) culture conditions via evaluating oxidative stress and endoplasmic reticulum stress (ERS). The RTECs (NRK-52E cells) were divided into six groups as follows: NG group, HG group, NG + H/R group, HG + H/R group, NG + Pio + H/R group, and HG + Pio + H/R group, among which cells in H/R groups were subjected to 4 h of hypoxia followed by 12 h of reoxygenation. After that, the cells were evaluated using the Cell Counting Kit-8 assay for the determination of their viability and flow cytometry assay for the detection of apoptosis. The levels of superoxide dismutase (SOD), glutathione reductase (GSH), catalase (CAT), and malondialdehyde (MDA) were determined via colorimetric chemical assays. In addition, the expression of ERS-associated proteins, i.e. ATF4, ATF6, GRP78, and CHOP, was determined via western blotting. A HG environment could reduce the viability and increase the apoptotic rate of NRK-52E cells with increased MDA levels and decreased SOD, CAT, and GSH levels, and upregulate the expression of ERS-associated proteins, i.e. ATF4, ATF6, and GRP78. H/R injury could further aggravate changes in the above indicators, but pioglitazone could significantly reverse such changes and alleviate cell injury. Thus, Pioglitazone exhibits a cytoprotective effect on RTECs against H/R injury under NG or HG culture conditions by inhibiting oxidative stress and ERS.

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Section: Discussionmentioning

confidence: 94%

Pioglitazone Attenuates Reoxygenation Injury in Renal Tubular NRK-52E Cells Exposed to High Glucose via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Zou

Zhou

et al. 2020

Front. Pharmacol.

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“…The surgical induction of I/R injury was performed as follows: animals were anesthetized with diazepam (subcutaneous—5 mg/kg), ketamine (intraperitoneal—75 mg/kg), and xylazine (intraperitoneal—10 mg/kg), submitted to a surgical procedure of supraceliac aorta clamping for 30 min to induce complete abdominal ischemia, as previously described [ 8 ]. As control, animals of the sham-operated groups underwent the surgical procedure for aorta isolation, without aortic clamping and blood flow interruption.…”

Section: Methodsmentioning

confidence: 99%

“…Several mediators of inflammation and vascular diseases have been demonstrated to interact with metabolic pathways and promising results have been obtained employing antidiabetic treatments in an experimental animal model of I/R [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells

Barisione

Verzola

Garibaldi

et al. 2021

IJMS

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During visceral interventions, the transient clampage of supraceliac aorta causes ischemia/reperfusion (I/R) in kidneys, sometime resulting in acute renal failure; preclinical studies identified redox imbalance as the main driver of I/R injury. However, in humans, the metabolic/inflammatory responses seem to prevail on oxidative stress. We investigated myostatin (Mstn) and proprotein convertase subtilisin/kexin type 9 (PCSK9), proatherogenic mediators, during renal I/R. Compared to sham-operated animals, the kidneys of rats who had experienced ischemia (30 min) had higher Mstn and PCSK9 expression after 4 h of reperfusion. After 24 h, they displayed tubular necrosis, increased nitrotyrosine positivity, and nuclear peroxisome proliferator-activated receptor gamma coactivator-1alpha relocation, markers of oxidative stress and mitochondria imbalance. Mstn immunopositivity was increased in tubuli, while PCSK9 immunosignal was depleted; systemically, PCSK9 was higher in plasma from I/R rats. In HK-2 cells, both ischemia and reperfusion enhanced reactive oxygen species production and mitochondrial dysfunction. H2O2 upregulated Mstn and PCSK9 mRNA after 1 and 3.5 h, respectively. Accordingly, ischemia early induced Mstn and PCSK9 mRNA; during reperfusion Mstn was augmented and PCSK9 decreased. Mstn treatment early increased PCSK9 expression (within 8 h), to diminish over time; finally, Mstn silencing restrained ischemia-induced PCSK9. Our study demonstrates that renal I/R enhances Mstn and PCSK9 expression and that Mstn induces PCSK9, suggesting them as therapeutic targets for vascular protection during visceral surgery.

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“…Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, has exhibited anti-inflammatory effects [6,7] and has been shown to prevent acute liver injury induced by ethanol and LPS through the suppression of TNF-α production in rats [8]. In addition, pioglitazone partially reduces a secondary inflammatory response in the ischemic insult especially in the endothelial and perivascular tissues of rats [9]. Activation of the PPAR-γ receptor by pioglitazone protects against neuronal and cognitive degeneration elicited by binge alcohol exposure linked to inhibition of pro-inflammatory cytokines in rats [10].…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats

Yeh

Wang

Kaizaki

et al. 2021

IJMS

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Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.

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Inflammatory Response Modulation through a PPARγ Agonist during Surgically Induced Visceral Ischemia in an Animal Model

Cited by 9 publications

References 27 publications

Pioglitazone Attenuates Reoxygenation Injury in Renal Tubular NRK-52E Cells Exposed to High Glucose via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Pioglitazone Attenuates Reoxygenation Injury in Renal Tubular NRK-52E Cells Exposed to High Glucose via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells

Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment, Brain Inflammation, White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats

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