Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation

Kutanıs, Dilek; Ertürk, Engin; Beşir, Ahmet; Demirci, Yücel; Kayır, Selçuk; Akdoğan, Ali; Kural, Birgül Vanizör; Bahat, Zümrüt; Canyılmaz, Emine; Kara, Hanife

doi:10.1016/j.jclinane.2016.06.031

Cited by 16 publications

(6 citation statements)

References 27 publications

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“…In the current study, exposure to IR led to an elevation in the expression of PARP‐1, as shown by western blot analysis, aiming to counteract the excessive DNA strand breaks caused by IR‐induced oxidative stress. These findings are consistent with previous research where the elevated level of free radicals and the degradation of endogenous antioxidant enzymes by IR can eventually lead to DNA damage causing the PARP‐1 enzyme to become overactive 24,54 . RSV caused a reduction/ablation of PARP‐1 expression, which in turn might boost NAD + levels and consequently lead to SIRT‐1 activation, an effect which was abolished by using NAM.…”

Section: Discussionsupporting

confidence: 92%

“…These findings are consistent with previous research where the elevated level of free radicals and the degradation of endogenous antioxidant enzymes by IR can eventually lead to DNA damage causing the PARP-1 enzyme to become overactive. 24,54 RSV caused a reduction/ablation of PARP-1 expression, which in turn might boost NAD + levels and consequently lead to SIRT-1 activation, an effect which was abolished by using NAM. PARP is involved in the expression of several cytokines and other inflammatory mediators, as well as the recruitment of the inducible nitric oxide synthase (iNOS) enzyme involved in the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of radiation‐induced liver damage by modulation of SIRT‐1 activity: In vivo rat model

El-Sheikh

Abdel‐Naby

El-Hazek

et al. 2022

Cell Biochemistry & Function

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Silent information regulator 1 (SIRT-1), a nicotinamide adenine dinucleotidedependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT-1 in regulating forkhead box O/poly ADP-ribose polymerase-1 (FOXO-1/PARP-1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT-1 activity toward radiation sensitivity.In the present study, the SIRT-1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT-1 activator) versus nicotinamide (NAM, SIRT-1 inhibitor) in case of liver damage induced by whole-body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT-1, FOXO-1, and cleaved PARP-1 in the liver was analyzed. RSV improved radiation-induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase-3, lactate dehydrogenase, complex-I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT-1, whereas cleaved PARP-1 and FOXO-1 were suppressed. These protective effects were suppressed by inhibition of SIRT-1 activity using NAM. These findings suggest that RSV can attenuate radiation-induced hepatic injury by reducing apoptosis and inflammation via SIRT-1 activity modulation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Regulation of radiation‐induced liver damage by modulation of SIRT‐1 activity: In vivo rat model

El-Sheikh

Abdel‐Naby

El-Hazek

et al. 2022

Cell Biochemistry & Function

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“…Dexmedetomidine (DEX) is a selective α 2 -adrenoreceptor (α 2 -AR) agonist with sedative, analgesic, and anti-anxiety effects ( Shen et al, 2017 ). In addition, several animal studies have noted antioxidant, anti-apoptosis, and anti-inflammatory effects of DEX, although some of the molecular pathways remain unclear ( Kutanis et al, 2016 ; Wang et al, 2019 ). Many studies have demonstrated that DEX can decrease endotoxin-induced upregulation of inflammatory molecules and attenuate renal function associated with AKI ( Lai et al, 2009 ; Liang et al, 2017 ; Qiu et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Enhances Autophagy via α2-AR/AMPK/mTOR Pathway to Inhibit the Activation of NLRP3 Inflammasome and Subsequently Alleviates Lipopolysaccharide-Induced Acute Kidney Injury

et al. 2020

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Background: Acute kidney injury (AKI) is a severe complication of sepsis; however, no effective drugs have been found. Activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome is a major pathogenic mechanism of AKI induced by lipopolysaccharide (LPS). Autophagy, a process of intracellular degradation related to renal homeostasis, effectively restricts inflammatory responses. Herein, we explored the potential protective mechanisms of dexmedetomidine (DEX), which has confirmed antiinflammatory effects, on LPS-induced AKI. Methods: AKI was induced in rats by injecting 10 mg/kg of LPS intraperitoneally (i.p.). Wistar rats received intraperitoneal injections of DEX (30 µg/kg) 30 min before an intraperitoneal injection of LPS. Atipamezole (ATI) (250 µg/kg) and 3-methyladenine (3-MA) (15 mg/kg) were intraperitoneally injected 30 min before the DEX injection. Results: DEX significantly attenuated renal injury. Furthermore, DEX decreased activation of the NLRP3 inflammasome and expression of interleukins 1b and 18. In addition, autophagy-related protein and gene analysis indicated that DEX could significantly enhance autophagy. Finally, we verified the pharmacological effects of DEX on the 5′adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathway. Atip and 3-MA significantly reversed the protective effects of DEX. Conclusions: Our results suggest that the protective effects of DEX were mediated by enhanced autophagy via the a 2-adrenoreceptor/AMPK/mTOR pathway, which decreased

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“…One of the difficulties in evaluating the anti-inflammatory effects of Dex is determining its dose. In previous studies, the protective effect [35,39,48,[54][55][56][57][58][59]. In practice, lower doses may not protect against damage, whereas hemodynamic adverse effects may occur at higher doses.…”

Section: Discussionmentioning

confidence: 92%

Tailored Therapeutic Doses of Dexmedetomidine in Evolving Neuroinflammation after Traumatic Brain Injury

et al. 2021

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Background: Understanding the secondary damage mechanisms of traumatic brain injury (TBI) is essential for developing new therapeutic approaches. Neuroinflammation has a pivotal role in secondary brain injury after TBI. Activation of NLRP3 inflammasome complexes results in the secretion of proinflammatory mediators and, in addition, later in the response, microglial activation and migration of the peripheral immune cells into the injured brain are observed. Therefore, these components involved in the inflammatory process are becoming a new treatment target in TBI. Dexmedetomidine (Dex) is an effective drug, widely used over the past few years in neurocritical care units and during surgical operations for sedation and analgesia, and has anti-inflammatory effects, which are shown in in vivo studies. The aim of this original research is to discuss the anti-inflammatory effects of different Dex doses over time in TBI. Methods:Brain injury was performed by using a weight-drop model. Half an hour after the trauma, intraperitoneal saline was injected into the control groups and 40 and 200 μg/kg of Dex were given to the drug groups. Neurological evaluations were performed with the modified Neurological Severity Score before being killed. Then, the mice were killed on the first or the third day after TBI and histopathologic (hematoxylin-eosin) and immunofluorescent (Iba1, NLRP3, interleukin-1β, and CD3) findings of the brain tissues were examined. Nonparametric data were analyzed by using the Kruskal-Wallis test for multiple comparisons, and the Mann-Whitney U-test was done for comparing two groups. The results are presented as mean ± standard error of mean. Results:The results showed that low doses of Dex suppress NLRP3 and interleukin-1β in both terms. Additionally, high doses of Dex cause a remarkable decrease in the migration and motility of microglial cells and T cells in the late phase following TBI. Interestingly, the immune cells were influenced by only high-dose Dex in the late phase of TBI and it also improves neurologic outcome in the same period. Conclusions:In the mice head trauma model, different doses of Dex attenuate neuroinflammation by suppressing distinct components of the neuroinflammatory process in a different timecourse that contributes to neurologic recovery. These results suggest that Dex may be an appropriate choice for sedation and analgesia in patients with TBI.

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Dexmedetomidine acts as an oxidative damage prophylactic in rats exposed to ionizing radiation

Cited by 16 publications

References 27 publications

Regulation of radiation‐induced liver damage by modulation of SIRT‐1 activity: In vivo rat model

Regulation of radiation‐induced liver damage by modulation of SIRT‐1 activity: In vivo rat model

Dexmedetomidine Enhances Autophagy via α2-AR/AMPK/mTOR Pathway to Inhibit the Activation of NLRP3 Inflammasome and Subsequently Alleviates Lipopolysaccharide-Induced Acute Kidney Injury

Tailored Therapeutic Doses of Dexmedetomidine in Evolving Neuroinflammation after Traumatic Brain Injury

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