Pharmacology of Ischemia–Reperfusion. Translational Research Considerations

Prieto‐Moure, Beatriz; Lloris‐Carsí, José Miguel; Barrios, Carlos; Toledo-Pereyra, L. H.; Lajara-Romance, Jose María; Berda-Antolí, M.; Lloris-Cejalvo, José Miguel; Cejalvo‐Lapeña, Dolores

doi:10.3109/08941939.2015.1119219

Cited by 14 publications

(10 citation statements)

References 110 publications

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“…The IPC is a phenomenon triggered by short episodes of ischemia and reperfusion before a long ischemia and reperfusion. The beneficial role of IPC is clearly evident from the literature, and it has been tested in different organs including intestine, brain, spinal cord, kidney, lung, liver, and human heart [19][20][21][22][23][24][25][26]. There are some studies explaining the changes in the neutrophil behavior after IPC.…”

Section: Introductionmentioning

confidence: 99%

Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases

Tahir

Arshid

Fontes

et al. 2020

IJMS

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Intestinal ischemia reperfusion injury (iIRI) is a severe clinical condition presenting high morbidity and mortality worldwide. Some of the systemic consequences of IRI can be prevented by applying ischemic preconditioning (IPC), a series of short ischemia/reperfusion events preceding the major ischemia. Although neutrophils are key players in the pathophysiology of ischemic injuries, neither the dysregulation presented by these cells in iIRI nor the protective effect of iIPC have their regulation mechanisms fully understood. Protein phosphorylation, as well as the regulation of the respective phosphatases and kinases are responsible for regulating a large number of cellular functions in the inflammatory response. Moreover, in previous work we found hydrolases and transferases to be modulated in iIR and iIPC, suggesting the possible involvement of phosphatases and kinases in the process. Therefore, in the present study, we analyzed the phosphoproteome of neutrophils from rats submitted to mesenteric ischemia and reperfusion, either submitted or not to IPC, compared to quiescent controls and sham laparotomy. Proteomic analysis was performed by multi-step enrichment of phosphopeptides, isobaric labeling, and LC-MS/MS analysis. Bioinformatics was used to determine phosphosite and phosphopeptide abundance and clustering, as well as kinases and phosphatases sites and domains. We found that most of the phosphorylation-regulated proteins are involved in apoptosis and migration, and most of the regulatory kinases belong to CAMK and CMGC families. An interesting finding revealed groups of proteins that are modulated by iIR, but such modulation can be prevented by iIPC. Among the regulated proteins related to the iIPC protective effect, Vamp8 and Inpp5d/Ship are discussed as possible candidates for control of the iIR damage.

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Section: Introductionmentioning

confidence: 99%

Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases

Tahir

Arshid

Fontes

et al. 2020

IJMS

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“…These ROS cause cellular damage by attacking cellular membranes through the peroxidation of polyunsaturated fatty acids [ 6 ]. Several antioxidants have been found to be effective in the prevention of oxidative injury and inflammation in ovarian tissues exposed to I/R injury [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Glycyrrhetinic Acid and Chrysin against Ischemia-Reperfusion Injury in Rat Ovaries

Melekoğlu

Çiftçi

Eraslan

et al. 2018

BioMed Research International

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Objective To evaluate the protective effects of glycyrrhetinic acid (GA) and chrysin (CH) on experimental ischemia-reperfusion (I/R) injury in rat ovaries using tissue oxidative stress marker levels, hormone levels, and histopathological scores. Methods Sixty healthy rats were randomly divided into six equal groups: control, I/R, I/R + CH (50 mg/kg/day), I/R + GA (100 mg/kg/day), CH (50 mg/kg/day), and GA (100 mg/kg/day). Biochemical, hormonal, and histopathological evaluations were performed on blood and tissue samples 14 days after CH and GA treatment. Results The antioxidant defense system parameters were significantly higher in the ovarian tissues of the I/R + CH and I/R + GA groups than in those of the I/R group. Serum follicle-stimulating hormone levels were significantly reduced, and serum anti-Müllerian hormone levels were significantly increased in rats treated with CH and GA compared with those in the I/R group. Additionally, the histopathological scores of the I/R + CH and I/R + GA groups were significantly improved compared with those of the I/R group. Conclusions The significant improvements in tissue oxidative stress parameters, serum hormone levels, and histological scores observed in this study indicate that treatment with CH or GA may be a conservative approach to prevent I/R injury in adnexal torsion cases after the ovarian detorsion procedure.

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“…In animal models, xanthine oxidase may cause kidney fibrosis through inflammation, endothelial dysfunction, oxidative stress, and activation of the renin-angiotensin system [25]. In some studies, both allopurinol [26][27][28][29] and febuxosate [30][31][32][33][34] show renal protections independent from their UA lowering effect. Our present results did not support renal protection of the UA-lowering agents with statistical significance.…”

Section: Discussionmentioning

confidence: 99%

The effect of trajectory of serum uric acid on patients and renal outcomes in patients with stage-3 chronic kidney disease

Tsai

Chen

et al. 2020

Preprint

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Background Uric acid (UA) is associated with renal and patient survivals but the causal association in nature remains unclear. Also, no finding is yet available regarding longitudinal UA control (trajectory). Methods We enrolled 808 subjects diagnosed with stage 3 chronic kidney disease from 2007 to 2017. We plotted the mean UA over a period of 6 months with a minimum of three samples of UA was required. From the sampled points, we generated for each patient an interpolated line by joining mean values of the UA levels over time. And from the lines from all patients, we classified them into three groups of trajectories (low, medium and high) through group-based trajectory modeling, and then we further separated into either a treatment or no-treatment subgroups. Due to multiple comparisons, we performed post hoc analysis by Bonferroni adjustment. Using the univariate competing-risks regression, we calculated the competing risk analysis with subdistribution hazard ratio of possible confounders. Results All of the 6 trajectories appeared as gradually falling functions with time without any of the curves crossed over one another. For all-cause mortality risk, none of the variables (including age, gender, coronary arterial disease, cerebrovascular disease, diabetes mellitus, renin-angiotensin-aldosterone system inhibitors, trajectories of UA, and treatment of UA) was statistically significant. All 6 trajectories appeared as steady curve without crossovers among them over the entire period of follow-up. Patients with DM were statistically more likely to undergo dialysis. There was only a trend that the on-treatment trajectories, compared to their no-treatment trajectories, had lower risks for dialysis. There was no effect of UA control on patients’ survival. Conclusions Initial treatment of UA is utterly important for UA control. However, the long-term effects on patients and renal survivals maybe minor without statistical significance. Keyword: uric acid, patient survival, renal survival, long-term effect, trajectory, competing risk analysis

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Pharmacology of Ischemia–Reperfusion. Translational Research Considerations

Cited by 14 publications

References 110 publications

Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases

Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases

The Protective Effects of Glycyrrhetinic Acid and Chrysin against Ischemia-Reperfusion Injury in Rat Ovaries

The effect of trajectory of serum uric acid on patients and renal outcomes in patients with stage-3 chronic kidney disease

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