Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure

Czarnecka, Anna; Milewski, Krzysztof; Jaźwiec, Radosław

doi:10.1007/s12640-016-9668-7

Cited by 10 publications

(14 citation statements)

References 56 publications

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“…A significant impact of ADMA on CBF regulation under resting and pathologically changed conditions by NOS inhibition has been previously indicated (Iadecola 1993). Previously, we demonstrated that TAA administration resulted in a significant increase in the ADMA concentration in microdialysates of the prefrontal cortex, brain tissue homogenate and peripheral blood Czarnecka et al 2017b). Concentration of ADMA is higher in cerebellum and blood vessels than in other regions of the brain (Ueno et al 1992), what may explain why in TAA rats L-arginine led to dilation of the MCAs and improved CBF more effectively in the cerebellum than in the prefrontal cortex.…”

Section: Discussionsupporting

confidence: 55%

“…; Czarnecka et al . ). Concentration of ADMA is higher in cerebellum and blood vessels than in other regions of the brain (Ueno et al .…”

Section: Discussionmentioning

confidence: 97%

“…Based on power calculations on previously published results (microdialysis: Czarnecka et al 2017b;MCAs reactivity: Aleksandrowicz et al 2017) it was assumed that a sample size of n = 5 per group would be necessary and sufficient to provide meaningful results to achieve 90% power at a significance level of 5%. Animals were divided into two experimental groups: control and TAAtreated rats.…”

Section: Study Design and Animal Groupsmentioning

confidence: 99%

“…Bilateral microdialysis of the prefrontal cortex was performed 24 h after the last TAA administration as described previously (Czarnecka et al 2017b). The rats were anesthetized with 5% isoflurane in air within 2 min and then anesthesia was maintained during the whole experiment with a 2% isoflurane-air mixture.…”

Section: Microdialysis Of the Rat Prefrontal Cortexmentioning

confidence: 99%

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Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L‐glutamine and asymmetric dimethylarginine in L‐arginine‐induced response

Czarnecka

Aleksandrowicz

Jasiński

et al. 2018

Journal of Neurochemistry

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Cerebral blood flow (CBF) is impaired in acute liver failure (ALF), however, the complexity of the underlying mechanisms has often led to inconclusive interpretations. Regulation of CBF depends at least partially on variations in the local brain L-arginine concentration and/or its metabolic rate. In ALF, other factors, like an increased concentration of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor and elevated level of L-glutamine, may contribute to CBF alteration. This study demonstrated strong differences in the reactivity of the middle cerebral arteries and their response to extravascular L-arginine application between vessels isolated from rats with thioacetamide (TAA)-induced ALF and control animals. Our results also showed the decrease in the cerebral perfusion in TAA rats measured by arterial spin labeling perfusion magnetic resonance. Subsequently, we aimed to investigate the importance of balance between the concentration of ADMA and L-arginine in the CBF regulation. In vivo, intraperitoneal L-arginine administration in TAA rats corrected: (i) decrease in cerebral perfusion, (ii) decrease in brain extracellular L-arginine/ADMA ratio and (iii) increase in brain L-glutamine concentration. Our study implicates that impaired vascular tone of cerebral arteries is most likely associated with exposure to high ADMA and L-glutamine levels resulting in limited availability of L-arginine and might be responsible for reduced cerebral perfusion observed in ALF.

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Section: Discussionsupporting

confidence: 55%

“…; Czarnecka et al . ). Concentration of ADMA is higher in cerebellum and blood vessels than in other regions of the brain (Ueno et al .…”

Section: Discussionmentioning

confidence: 97%

Section: Study Design and Animal Groupsmentioning

confidence: 99%

Section: Microdialysis Of the Rat Prefrontal Cortexmentioning

confidence: 99%

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Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L‐glutamine and asymmetric dimethylarginine in L‐arginine‐induced response

Czarnecka

Aleksandrowicz

Jasiński

et al. 2018

Journal of Neurochemistry

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“…Taurine has an antioxidant effect, restores the expression of endothelial NO synthase, which is the main endothelium protective pharmacodynamic effect (Battson et al 2017, Ito et al 2012, Rukan et al 2013. Ademethionine is involved in transmethylation, transsulfurization, and transamination reactions, and by inhibiting the PRMT enzyme and preventing the ADMA formation, leads to an increased expression of the eNOS enzyme (Czarnecka et al 2017, Kim et al 2013, Sukhanov et al 2014, Tang et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological correction of endothelial dysfunction using ademethionin and taurine

Khadieva¹,

Pokrovskaya²,

Belousova³

2019

RRP

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Introduction: Рharmacological correction of endothelial dysfunction is a urgent problem of modern medicine. Materials and methods: Endothelial dysfunction was simulated in male rats using the e-NOS inhibitor L-NAME (25 mg/kg/day intraperitoneally, for 7 days). Simulation of ADMA-like preeclampsia was performed by intraperitoneal injection of L-NAME to females in the same doses for 7 days (14-20th days of pregnancy). These pathologies were corrected by administering ademethionine in dose 150 mg/kg and taurine at a dose of 260 mg/kg, as well as their combination at the same doses, intragastrically, through an atraumatic probe, once a day. Results: In the group with use of taurine at a dose of 260 mg/kg the coefficient of endothelial dysfunction decreased to the level of intact animals. Use of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg combined resulted in the most pronounced endothelioprotective effect on the ADMA-like preeclampsia model. The coefficient of endothelial dysfunction decreased more than when using monotherapy of these drugs. Morphological studies of myocardiocytes showed that the combination of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg prevented an increase in the cross-section of cardiomyocytes. Discussion: Possibly, ademethionine and taurine have an endothelioprotective effect because of their ability to decrease hyperhomocysteinemia. Conclusion: The investigated drugs showed pronounced endothelioprotective activity and can be recommended for further pre-clinical studies.

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Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association?

Czarnecka

Milewski

2016

Neurochem Res

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The methylated derivative of l-arginine, asymmetric dimethylarginine (ADMA) is synthesized in different mammalian tissues including the brain. ADMA acts as an endogenous, nonselective, competitive inhibitor of all three isoforms of nitric oxide synthase (NOS) and may limit l-arginine supply from the plasma to the enzyme via reducing its transport by cationic amino acid transporters. Hepatic encephalopathy (HE) is a relatively frequently diagnosed complex neuropsychiatric syndrome associated with acute or chronic liver failure, characterized by symptoms linked with impaired brain function leading to neurological disabilities. The l-arginine—nitric oxide (NO) pathway is crucially involved in the pathomechanism of HE via modulating important cerebral processes that are thought to contribute to the major HE symptoms. Specifically, activation of this pathway in acute HE leads to an increase in NO production and free radical formation, thus, contributing to astrocytic swelling and cerebral edema. Moreover, the NO-cGMP pathway seems to be involved in cerebral blood flow (CBF) regulation, altered in HE. For this reason, depressed NO-cGMP signaling accompanying chronic HE and ensuing cGMP deficit contributes to the cognitive and motor failure. However, it should be remembered that ADMA, a relatively little known element limiting NO synthesis in HE, may also influence the NO-cGMP pathway regulation. In this review, we will discuss the contribution of ADMA to the regulation of the NO-cGMP pathway in the brain, correlation of ADMA level with CBF and cognitive alterations observed during HE progression in patients and/or animal models of HE.

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Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure

Cited by 10 publications

References 56 publications

Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L‐glutamine and asymmetric dimethylarginine in L‐arginine‐induced response

Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L‐glutamine and asymmetric dimethylarginine in L‐arginine‐induced response

Pharmacological correction of endothelial dysfunction using ademethionin and taurine

Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association?

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