β-Alanine uptake is upregulated in FeC13-induced cortical scars

Robitaille, Yves; Kemball, Kevin; Sherwin, Allan L.

doi:10.1016/0022-510x(95)00214-m

Cited by 4 publications

(1 citation statement)

References 39 publications

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“…It is important to emphasize that GAD is highly sensitive to free radicals, and its inhibition amplifies epileptogenesis induced by FeCl 3 (Robitaille et al. 1995 ). In this way, it is probable that the antioxidant activity of lasiodiplodan (Giese et al.…”

Section: Discussionmentioning

confidence: 99%

Intracerebroventricular administration of the (1→6)-β- d -glucan (lasiodiplodan) in male rats prevents d -penicillamine-induced behavioral alterations and lipoperoxidation in the cortex

Malfatti

Santos

Wouk

et al. 2017

Pharmaceutical Biology

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Context: Lasiodiplodan, an exocellular (1→6)-β-d-glucan of molecular weight >1.4 × 106 Da produced by MMPI strain of Lasiodiplodia theobromae (Pat.) Griffon & Maubl. (Brotyosphaeriaceae) is known to exhibit anti-proliferative activity on breast cancer cells (MCF-7), anticoagulant activity when sulfonylated, and reduction in transaminase activity when administered in rats.Objective: The effect of intracerebroventricular (I.C.V) injection of lasiodiplodan on neurotoxicity and behavioural changes induced by d-penicillamine was investigated.Materials and methods: Twenty-four male Wistar rats were initially separated in groups of six and treated with 0.15 μmol/μL of NaCl (Groups Ct and d-Pen) and 0.01 μg/μL of lasiodiplodan (Groups Las and Las + d-Pen). After 15 min, they received 6 μmol/μL of NaCl (Groups Ct and Las) and 2 μmol/μL of d-penicillamine (Groups d-Pen and Las + d-Pen). The animal behavior was observed in an open-field test for 60 min. Twenty-four h later, the animals were sacrificed and histopathological analysis and Thiobarbituric acid reactive substances (TBARS) production measurements were performed.Results: Lasiodiplodan prevented neurotoxicity induced by d-penicillamine significantly reducing the production of TBARS (308%; p < 0.05), and behavioural signs; convulsive and pre-convulsive. No histopathological alterations in the cerebral cortex were observed.Discussion and conclusion: The reduction of TBARS production and convulsive episodes suggests that the protector effect provided by lasiodiplodan passes thought an antioxidant path, possibly interfering in a cascade of neurochemical events, triggering cell death and convulsive episodes. These results demonstrated that lasiodiplodan can be effective in treating neurotoxicity, and reducing damage triggered by convulsions in neuropathies related to GABAergic system.

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Section: Discussionmentioning

confidence: 99%

Intracerebroventricular administration of the (1→6)-β- d -glucan (lasiodiplodan) in male rats prevents d -penicillamine-induced behavioral alterations and lipoperoxidation in the cortex

Malfatti

Santos

Wouk

et al. 2017

Pharmaceutical Biology

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A neuronal disruption in redox homeostasis elicited by ammonia alters the glycine/glutamate (GABA) cycle and contributes to MMA-induced excitability

et al. 2016

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Hyperammonemia is a common finding in children with methylmalonic acidemia. However, its contribution to methylmalonate-induced excitotoxicty is poorly understood. The aim of this study was to evaluate the mechanisms by which ammonia influences in the neurotoxicity induced by methylmalonate (MMA) in mice. The effects of ammonium chloride (NH4Cl 3, 6, and 12 mmol/kg; s.c.) on electroencephalographic (EEG) and behavioral convulsions induced by MMA (0.3, 0.66, and 1 µmol/2 µL, i.c.v.) were observed in mice. After, ammonia, TNF-α, IL1β, IL-6, nitrite/nitrate (NOx) levels, mitochondrial potential (ΔΨ), reactive oxygen species (ROS) generation, Methyl-Tetrazolium (MTT) reduction, succinate dehydrogenase (SDH), and Na(+), K(+)-ATPase activity levels were measured in the cerebral cortex. The binding of [(3)H]flunitrazepam, release of glutamate-GABA; glutamate decarboxylase (GAD) and glutamine synthetase (GS) activity and neuronal damage [opening of blood brain barrier (BBB) permeability and cellular death volume] were also measured. EEG recordings showed that an intermediate dose of NH4Cl (6 mmol/kg) increased the duration of convulsive episodes induced by MMA (0.66 μmol/2 μL i.c.v). NH4Cl (6 mmol/kg) administration also induced neuronal ammonia and NOx increase, as well as mitochondrial ROS generation throughout oxidation of 2,7-dichlorofluorescein diacetate (DCFH-DA) to DCF-RS, followed by GS and GAD inhibition. The NH4Cl plus MMA administration did not alter cytokine levels, plasma fluorescein extravasation, or neuronal damage. However, it potentiated DCF-RS levels, decreased the ΔΨ potential, reduced MTT, inhibited SDH activity, and increased Na(+), K(+)-ATPase activity. NH4Cl also altered the GABA cycle characterized by GS and GAD activity inhibition, [(3)H]flunitrazepam binding, and GABA release after MMA injection. On the basis of our findings, the changes in ROS and reactive nitrogen species (RNS) levels elicited by ammonia alter the glycine/glutamate (GABA) cycle and contribute to MMA-induced excitability.

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Convulsions induced by methylmalonic acid are associated with glutamic acid decarboxylase inhibition in rats: A role for GABA in the seizures presented by methylmalonic acidemic patients?

Malfatti¹,

Perry²,

Schweigert³

et al. 2007

Neuroscience

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β-Alanine uptake is upregulated in FeC13-induced cortical scars

Cited by 4 publications

References 39 publications

Intracerebroventricular administration of the (1→6)-β- d -glucan (lasiodiplodan) in male rats prevents d -penicillamine-induced behavioral alterations and lipoperoxidation in the cortex

Intracerebroventricular administration of the (1→6)-β- d -glucan (lasiodiplodan) in male rats prevents d -penicillamine-induced behavioral alterations and lipoperoxidation in the cortex

A neuronal disruption in redox homeostasis elicited by ammonia alters the glycine/glutamate (GABA) cycle and contributes to MMA-induced excitability

Convulsions induced by methylmalonic acid are associated with glutamic acid decarboxylase inhibition in rats: A role for GABA in the seizures presented by methylmalonic acidemic patients?

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