Effect of PJ-34 PARP-Inhibitor on Rat Liver Microcirculation and Antioxidant Status

Szíjártó, Attila; Batmunkh, Enkhjargal; Hahn, Oszkár; Mihály, Zsuzsanna; Kreiss, Adám; Kiss, András; Lotz, Gábor; Schaff, Zsuzsa; Váli, László; Blázovics, Anna; Gerö, Domokos; Szabó, Csaba; Kempler, Péter

doi:10.1016/j.jss.2006.08.003

Cited by 12 publications

(14 citation statements)

References 38 publications

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“…It is involved in a wide range of physiological processes including DNA repair, gene transcription and genomic stability maintenance, cell cycle progression, and apoptosis [18]. Several studies showed that inhibition of PARP has a protective effect on various organs during I/R [12][13][14]19]. In this study, increased concentration of MDA, an index of oxidative stress, and activation of PARP were strongly associated with increased apoptosis in the bladder after AUR and subsequent empting.…”

Section: Discussionsupporting

confidence: 51%

“…This is the main limitation of the present study. However, several recent reports have indicated that AUR not only induces bladder damage, but also induces functional and structural impairment of the heart, liver, and kidney [35][36][37] and inhibition of PARP-attenuated damage to several organs such as brain, kidney, liver, and heart under I/R conditions [12][13][14]19]. Considering these reports, we presume that inhibition of PARP may have beneficial effects on attenuating damage to other organs aside from the bladder.…”

Section: Discussionmentioning

confidence: 80%

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PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

2011

Apoptosis

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It has been demonstrated that increases in poly(ADP-ribose) polymerase (PARP) activity causes damage to several organs under ischemia/reperfusion (I/R) conditions. The aims of this study were to investigate whether inhibition of PARP could suppress apoptosis in the bladder following acute urinary retention (AUR) and subsequent bladder emptying. Twelve-week-old male Sprague Dawley rats were divided into a control group, saline treated group, and 3-aminobenzamide (3-AB, a specific PARP inhibitor)-treated group. Sixty minutes after the administration of saline and 3-AB, the saline and 3-AB-treated groups had 60 min of over-distension and followed by 2 h of drainage. The degree of bladder apoptosis, levels of malondialdehyde (MDA), ATP and nicotinamide adenine dinucleotide (NAD+); expression of poly(ADP-ribose) (PAR), phosphorylation of protein kinase B (Akt); and levels of Bcl-2, Bax, and caspase 3 activity in the bladder were determined. Molecular and histological analyses showed that bladder apoptosis was associated with increases in the amount of PAR and decreases in ATP and NAD+ levels in the saline treated group. In addition, phosphorylated Akt and Bcl-2/Bax ratio were significantly decreased. The activity of caspase 3 was significantly increased in the saline treated group. Inhibition of PARP significantly increased the levels of ATP and NAD+, phosphorylation of Akt, and Bcl-2/Bax ratio, and significantly reduced the activation of caspase 3. As a result, apoptosis in the bladder was attenuated. These results indicate that PARP activation may be involved in apoptosis in the bladder induced by AUR and subsequent emptying via energy depletion and suppression of Akt activity.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 80%

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

2011

Apoptosis

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“…The operative procedure was performed as described previously [19]. Sixty min warm ischemia of the median and lateral lobes (lobes III-V, 65%-70% of the total hepatic mass) was induced by clamping of the portal veins, hepatic arteries, and biliary branches at the level of the hilum, using atraumatic microvascular clips.…”

Section: Operative Proceduresmentioning

confidence: 99%

Reduction of Liver Ischemia-Reperfusion Injury Via Glutamine Pretreatment

Stangl

Szíjártó

Ónody

et al. 2011

Journal of Surgical Research

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“…Így az enzimműködés gátlása a nekrózis elkerülé-sével és az apoptotikus folyamatok dominálásával a gyulladás csökkenéséhez vezethet [40], amelyet a korábbi, vitatott eredmények közül több megerősít [41]. Munkacsoportunk ezzel egybehangzó következtetésekre jutott saját, PJ-34 PARP-inhibitor-kezelést alkalmazó kísérle-tében, ahol a máj I-R károsodásának mérséklődésével párhuzamosan szignifi kánsan magasabb TUNEL-pozitivitás, a nekrózis hiánya és a máj szabadgyök-terhelésének csökkenése igazolódott [42].…”

Section: Kondicionáló Eljárások éS Máj Ischaemiareperfúzió -áLlatkíséunclassified

Szabad gyökök és a máj ischaemiás-reperfúziós károsodása

Szíjártó

2015

Orvosi Hetilap

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Az ischaemiás-reperfúziós károsodás kiemelkedő jelentősége számos szerv és klinikai szituáció esetén jól bizonyított. A posztoperatív komplikációk prevalenciáját, a célszerv sérülését és a szisztémás szövődmények előfordulását jelentő-sen meghatározó károsodás mediálásában központi szerep jut a szabad gyököknek. A szabadgyök-stresszre kimondottan érzékeny máj anatómiailag és patofi ziológiailag speciális ischaemiás-reperfúziós károsodása májsebészeti szempontból kulcsfontosságú. A reperfúziós károsodás mérséklésére számos kondicionáló eljárás (adaptív technikák, kémiai vegyületek) ismert. Jelen összefoglaló célja az ischaemiás-reperfúziós károsodás mérséklésére irányuló technikák áttekintése a szerző kutatócsoportjának eddigi munkássága (ischaemiás prekondicionálás, -perkondicionálás, glutaminszupplementáció, adenozin-, inozin-, levosimendan-, poli-ADP-ribóz polimerázgátlás szerepe) alapján, külö-nös tekintettel a máj ischaemiás-reperfúziós károsodására, valamint a szabad gyökök abban betöltött patofi ziológiai szerepére. Orv. Hetil., 2015, 156(47), 1904-1907. Kulcsszavak: ischaemiás-reperfúziós károsodás, máj, szabad gyök, ischaemiás prekondicionálás Free radicals and hepatic ischemia-reperfusionThe critical importance of the ischemic-reperfusive injury is well documented with regards to numerous organs and clinical conditions. Oxygen free radicals play a central role in the mediation of the injury, which dominantly infl uences the prevalence of postoperative complications, (long term) organ damage, and the potential manifestation of systemic reactions. The both anatomically and pathophysiologically unique ischemic-reperfusive injury of the liver, which is expressively vulnerable to free radicals, is of utmost importance in liver surgery. Several techniques (adaptive maneuvers, chemical agents) are known to ameliorate the reperfusive injury. Based on the prior research of the workgroup of the author, the aim of the current article is to overview the set of measures capable of attenuating ischemic-reperfusive injury (ischemic preconditioning, -perconditioning, administration of adenosine, -inosine, -levosimendan, and -poly-ADP-ribose-polymerase inhibitor), with special attention to the ischemic-reperfusive injury of the liver, as well as the special pathophysiological role of free radicals in mediating hepatic damage. Keywords: ischemia-reperfusion injury, liver, free radicals, ischemic preconditioningSzijártó, A. [Free radicals and hepatic ischemia-reperfusion]. Orv. Hetil., 2015, 156(47), 1904-1907. (Beérkezett: 2015 elfogadva: 2015. szeptember 23.) Rövidítések ADP = adenozin-difoszfát; ALP = alkalikus foszfatáz; ALT = alanin-aminotranszferáz; AMP = adenozin-monofoszfát; ATP = adenozin-triszfoszfát; CARS = compensatory anti-infl ammatory response syndrome; CX = (circumfl ex artery) bal szívkoszorúér körbefutó ága; DAMP = danger-associated molecular pattern; DNS = dezoxiribonukleinsav; GSH = glutation redukált forma; I-R = ischaemia-reperfúzió; ic. = intracelluláris; IFN-γ = interferon-γ; IL-1β = interleuk...

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Effect of PJ-34 PARP-Inhibitor on Rat Liver Microcirculation and Antioxidant Status

Cited by 12 publications

References 38 publications

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying

Reduction of Liver Ischemia-Reperfusion Injury Via Glutamine Pretreatment

Szabad gyökök és a máj ischaemiás-reperfúziós károsodása

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