2018
DOI: 10.1002/jcb.27332
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Oxidative damage in glutaric aciduria type I patients and the protective effects of l‐carnitine treatment

Abstract: The deficiency of the enzyme glutaryl-CoA dehydrogenase, known as glutaric acidemia type I (GA-I), leads to the accumulation of glutaric acid (GA) and glutarilcarnitine (C5DC) in the tissues and body fluids, unleashing important neurotoxic effects. l-carnitine (l-car) is recommended for the treatment of GA-I, aiming to induce the excretion of toxic metabolites. l-car has also demonstrated an important role as antioxidant and anti-inflammatory in some neurometabolic diseases. This study evaluated GA-I patients … Show more

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Cited by 34 publications
(16 citation statements)
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“…Although it is difficult to establish the relevance of each mechanism, the available data in the literature obtained from patients and animal models of GA I indicate that oxidative stress associated with neuroinflammation and excitotoxicity induced by the major accumulating organic acids (GA and 3−OHGA) play a key role in GA I pathophysiology. In this particular, recent findings obtained in blood and urine of patients with GA I support oxidative stress associated with inflammation in the pathogenesis of this disease (Guerreiro et al, 2018). Finally, investigation of the role of mitochondrial targeted antioxidants or compounds that increase mitochondrial biogenesis and dynamics, such as resveratrol and bezafibrate, firstly in Gcdh-/-mice tissues and cells from patients affected by GA I, may represent in the future novel therapies aiming to reduce reactive species levels and improve cellular respiration in this disease.…”
Section: Discussionsupporting
confidence: 57%
See 1 more Smart Citation
“…Although it is difficult to establish the relevance of each mechanism, the available data in the literature obtained from patients and animal models of GA I indicate that oxidative stress associated with neuroinflammation and excitotoxicity induced by the major accumulating organic acids (GA and 3−OHGA) play a key role in GA I pathophysiology. In this particular, recent findings obtained in blood and urine of patients with GA I support oxidative stress associated with inflammation in the pathogenesis of this disease (Guerreiro et al, 2018). Finally, investigation of the role of mitochondrial targeted antioxidants or compounds that increase mitochondrial biogenesis and dynamics, such as resveratrol and bezafibrate, firstly in Gcdh-/-mice tissues and cells from patients affected by GA I, may represent in the future novel therapies aiming to reduce reactive species levels and improve cellular respiration in this disease.…”
Section: Discussionsupporting
confidence: 57%
“…Diagnosis is mostly performed by elevated levels of GA and 3−OHGA in urine, as well as by glutarylcarnitine (C5DC) in blood of patients and confirmed by detection of deficient activity of GCDH activity in fibroblasts or leukocytes. The prognosis of GA I depends on early diagnosis and treatment based on restricted intake of Lys/protein, as well as by supplementation of L‐carnitine and in some cases arginine (Goodman et al, 2001; Kölker et al, 2002; Boy et al, 2017a; Guerreiro et al, 2018).…”
Section: Glutaric Acidemia Type I (Ga I)mentioning
confidence: 99%
“…Initial oral dosage of 100 mg L-carnitine/kg per day is commonly used. 24 The role of riboflavin is not clearly understood. All of our patients were given carnitine 100 mg/ kg/day, riboflavin 100 mg per day, pacitane (trihexyphenidyl) for severe dystonia, and a protein-restricted diet with restriction on lysine rich food items.…”
Section: Journal Of Pediatric Geneticsmentioning
confidence: 99%
“…Since cathepsin-d seems to be involved in inflammatory progression associated with redox homeostasis disruption and neurotoxicity (Egberts et al, 2004;Emert-Sedlak et al, 2005), it was hypothesized that high levels of this cytokine could be capable of triggering processes of apoptosis in MSUD (Scaini et al, 2017). It should be also noted that GA1 patients present high levels of proinflammatory cytokines (Guerreiro et al, 2018), as well as marked elevation of various parameters of oxidative stress in plasma and urine (Guerreiro et al, 2015;Mescka et al, 2013). In line with these findings, disturbance of redox homeostasis, glutamatergic neurotransmission, vascular alterations, and inflammatory processes were also observed in cortex and striatum of the GA1 knockout animal model (Amaral et al, 2015;Rodrigues et al, 2016;Wajner et al, 2019).…”
Section: We Investigated Various Markers Of Neurodegeneration and Infmentioning
confidence: 99%