RETRACTED: Vinpocetine ameliorates L-arginine induced acute pancreatitis via Sirt1/Nrf2/TNF pathway and inhibition of oxidative stress, inflammation, and apoptosis

Abdelzaher, Walaa Yehia; Ahmed, Sabreen Mahmoud; Welson, Nermeen N.; Marraiki, Najat; Batiha, Gaber El‐Saber; Kamel, Maha Yehia

doi:10.1016/j.biopha.2020.110976

Cited by 40 publications

(36 citation statements)

References 28 publications

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“…We assume that the inhibition of the NF-κB/TNF-α pathway mediates the therapeutic effect of rupatadine against AP consistent with (Chen et al 2019). The increased IL-1β production in the AP group was consistent with the finding of (Wu et al 2021) who reported that IL-1β production by activated neutrophils causes more tissue damage during AP progression. The precursor of IL-1β in AP is converted into an active form through the NLRP3 inflammasome (Hoque et al 2011), which is a cytosolic multiprotein complex responsible for the initiation of the inflammatory response as a part of the innate immune system.…”

Section: R a F Tsupporting

confidence: 91%

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

Mohamed

Mohammed

Khalaf

2022

Can. J. Physiol. Pharmacol.

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Acute pancreatitis (AP) is an abrupt inflammatory disorder causing high morbidity and mortality. As AP is an insidious medical emergency, a curative modality is required instead of a preventive measure. Thus, we investigated the possible curative effect of rupatadine on a rat model of AP. Rupatadine is a potent histamine receptor 1 (H1R) and platelet-activating factor (PAF) blocker. We used four groups of six Wistar rats as follows: the control group received vehicle; the rupatadine control group received rupatadine as 6 mg/kg orally; the AP group received l-arginine intraperitoneally, and the treatment group received rupatadine at 1, 6, and 24 h after l-arginine injection. The levels of serum amylase, pancreatic oxidative parameters, and pancreatic cytokines were measured. PAF, histamine, and myeloperoxidase levels were determined in the pancreas. Histopathological and immunohistochemical examinations were performed to determine nuclear factor kappa-B (NF-κB) and caspase 3 expressions. Oxidative damage and severe inflammation were detected in the pancreas of the AP group. Rupatadine reduced the oxidative damage and the levels of proinflammatory cytokines, PAF, histamine, myeloperoxidase, NF-κB, and caspase 3 expressions. It restored the pancreatic acini to almost normal condition. Rupatadine induced important anti-inflammatory and antiapoptotic effects against l-arginine-induced AP.

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Section: R a F Tsupporting

confidence: 91%

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

Mohamed

Mohammed

Khalaf

2022

Can. J. Physiol. Pharmacol.

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“…Oxidative stress is recognized as a major culprit in the pathogenesis of AP with impaired nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) signaling and downstream cascade being implicated as a crucial underlying mechanism [ 6 , 7 ]. Inflammatory events have been encountered in different models of AP, of which activated NF-κβ signaling has been a major trigger.…”

Section: Introductionmentioning

confidence: 99%

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

2022

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The currently available management strategies for acute pancreatitis are inadequately effective which calls for exploration of new approaches to treat this condition. Caffeic acid phenethyl ester (CAPE) is a major bioactive constituent of honeybee propolis with promising therapeutic and preventive applications. However, its pharmaceutical potential and clinical use are hindered by its poor water solubility and limited plasma stability. In this study, we aimed to prepare, characterize and evaluate a CAPE-loaded nanoliposomal formulation to improve the efficacy of CAPE for the management of acute pancreatitis. The CAPE-loaded nanoliposomes (CAPE-loaded-NL) were prepared by a thin layer evaporation technique and were optimized using three edge activators. CAPE-loaded-NL were characterized for their vesicle size (VS), zeta potential (ZP), encapsulation efficiency (EE), polydispersity index (PDI), crystalline state and morphology. The protective effect of the optimal CAPE-loaded-NL was evaluated in a rat model of acute pancreatitis induced by administering a single intraperitoneal injection of L-ornithine. Oral pretreatment with CAPE-loaded-NL significantly counteracted ornithine-induced elevation in serum activities of pancreatic digestive enzymes and pancreatic levels of malondialdehyde, nuclear factor kappa B (NF-κB) p65, tumor necrosis factor-alpha, nitrite/nitrate, cleaved caspase-3 and myeloperoxidase activity. Moreover, pretreatment with CAPE-loaded-NL significantly reinstated the ornithine-lowered glutathione reductase activity, glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 levels and ATP/ADP ratio, and potentiated the Bcl-2/Bax ratio in pancreatic tissue. CAPE-loaded-NL displayed superior antioxidant, anti-inflammatory and anti-apoptotic effects compared to free CAPE oral suspension and achieved a more potent correction of the derangements in serum amylase and pancreatic myeloperoxidase activities. The histological observations were in line with the biochemical findings. Our results suggest that CAPE-loaded-NL provide a promising interventional approach for acute pancreatitis mainly through the enhancement of the exerted antioxidant, anti-inflammatory and anti-apoptotic effects which may be mediated, at least in part, through modulation of Nrf2 and NF-κβ signaling.

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“…Moreover, it has been demonstrated that the intraperitoneal administration of arginine can induce selective and dose-dependent experimental pancreatitis in rats [ 27 ]. The action mechanism of arginine-induced pancreatitis was reported to be mediated by oxidative stress, inflammation, and apoptosis, among other processes [ 28 ]. High concentrations of proline have also been related to pancreatic alterations.…”

Section: Discussionmentioning

confidence: 99%

Untargeted Metabolomics for the Diagnosis of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis

et al. 2021

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Background and Objectives: The clinical manifestations and course of chronic pancreatitis (CP) are often nonspecific and variable, hampering diagnosis of the risk of exocrine pancreatic insufficiency (EPI). Development of new, reproducible, and non-invasive methods to diagnose EPI is therefore a major priority. The objective of this metabolomic study was to identify novel biomarkers associated with EPI. Materials and Methods: We analyzed 53 samples from patients with CP, 32 with and 21 without EPI, using an untargeted metabolomics workflow based on hydrophilic interaction chromatography coupled to high-resolution mass spectrometry. Principal component and partial least squares-discriminant analyses showed significant between-group differentiation, and univariate and multivariate analyses identified potential candidate metabolites that significantly differed between samples from CP patients with EPI and those without EPI. Results: Excellent results were obtained using a six-metabolic panel to diagnose the presence of EPI in CP patients (area under the ROC curve = 0.785). Conclusions: This study confirms the usefulness of metabolomics in this disease setting, allowing the identification of novel biomarkers to differentiate between the presence and absence of EPI in CP patients.

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RETRACTED: Vinpocetine ameliorates L-arginine induced acute pancreatitis via Sirt1/Nrf2/TNF pathway and inhibition of oxidative stress, inflammation, and apoptosis

Cited by 40 publications

References 28 publications

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

Untargeted Metabolomics for the Diagnosis of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis

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