Investigation of the Drug–Drug Interaction Between α-Lipoic Acid and Valproate via Mitochondrial β-oxidation

Phua, Lee Cheng; New, Lee Sun; Goh, Catherine W.; Neo, Aveline H.; Browne, Edward R.; Chan, Eric Chun Yong

doi:10.1007/s11095-008-9681-5

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…The histological features showed that ALA preserved the normal structure of the liver under valproate administration. The previous investigations reported a hepatoprotective effect of ALA [5][6][7]. A study reported that ALA protects hepatocytes by suppressing hepatic oxidative stress as well as downregulating the expression of hepatic pro-inflammatory cytokines, iNOS, and NF-κB [14].…”

Section: Discussionmentioning

confidence: 99%

“…ALA, known as thioctic acid or 1, 2-dithiolane-3-pentanoic acid (C 8 H 14 O 2 S 2 ), is an essential cofactor in mitochondrial dehydrogenase reactions, soluble in water and lipid, and widely distributed in the cellular membrane, cytosol, and extracellular space [4]. Several investigations have reported the hepatoprotective effects of ALA [5][6][7]; however, there is a lack of information regarding the role of ALA in sodium valproate-induced liver injury.…”

Section: Introductionmentioning

confidence: 99%

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Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice

et al. 2020

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Aim: This study examines the effect of alpha-lipoic acid (ALA) on sodium valproate-induced liver injury through histological features of mice liver tissue. Materials and Methods: Mice were divided into three groups; (1) vehicle group, (2) sodium valproate group, and (3) sodium valproate-ALA group. The vehicle group was injected with saline intraperitoneal (i.p.) for 28 days. The sodium valproate group was injected with sodium valproate 300 mg/kg, i.p. daily for 2 weeks, after which the vehicle was administered daily until day 28. The sodium valproate-ALA group was injected with sodium valproate 300 mg/kg daily for 2 weeks before the administration of ALA 100 mg/kg i.p. until day 28. The mice were euthanized, and the liver was extracted for histopathological examination. Results: Histopathological examination of the liver section of the vehicle group showed a normal structure of the liver. Two weeks after the administration of sodium valproate, histopathological examination showed an abnormal structure of the liver, with necrotic appearance and inflammatory cells. Moreover, treatment with ALA after the administration of sodium valproate notably ameliorated hepatic histopathological lesions and the liver structure corresponded to a normal liver structure. Conclusion: ALA ameliorates sodium valproate-induced liver injury in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice

et al. 2020

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“…Alternatively, it may relate to intrinsic properties of LA or its delivery system. 4–6 Yet unknown is if the PK variability and rapid clearance of LA impacts its therapeutic efficacy or has dosing implications for clinical trials or clinical use. Further development of LA may depend on improving its bioavailability and tolerability.…”

Section: Discussionmentioning

confidence: 99%

Lipoic acid pharmacokinetics at baseline and 1 year in secondary progressive MS

Bittner

Murchison

Koop

et al. 2017

Neurol Neuroimmunol Neuroinflamm

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“…Bioanalysis (2014) 6(3) addition, COA and its derivatives such as succinyl COA have previously been reported as IS in some literatures for both LC-MS/MS and HPLC ana lysis [15,23,24]. Optimization of both source and compound dependant parameters was carried out for analytes to maximize the signal intensity.…”

Section: Research Article | Damavandi Chan Kraus Ho and Kangmentioning

confidence: 99%

“…This has been largely attributed to the method's selectivity and sensitivity [13]. Consequently, liquid LC-MS/MS methods have been developed to separate and quantify several intracellular COA-esters [14,15]. These methods were demonstrated to be reliable for the determination of intracellular concentrations of COA-esters, and LC-MS/MS methods have since been introduced for the routine clinical laboratory screening of methyl malonyl acid and acylglycine in plasma and urine, for the screening of inborn error metabolisms such as methyl malonyl acidemia and PA [16][17][18].…”

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confidence: 99%

Development of an UPLC–MS/MS Method for Assaying The Enzymatic Activity of Propionyl Coenzyme-A Carboxylase

et al. 2014

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Propionic acidemia (PA) is a rare and life threatening metabolic disorder caused by deficiency of a mitochondrial biotin-dependent enzyme known as propionyl coenzyme-A carboxylase (PCC). PCC is required for the catabolism of metabolites that arise from the normal turnover of several essential amino acids (e.g., methionine, isoleucine, valine and threonine) and odd chain fatty acids [1,2]. Specifically, PCC catalyzes the carboxylation of the metabolic intermediate propionyl coenzyme-A (PP-COA) to methyl malonyl coenzyme-A (MM-COA) in the matrix of mitochondria (Figure 1) [3]. The native PCC holoenzyme comprises six a and six b subunits [4]. Studies on the biochemical aspects of PCC have shown that PA can occur in patients that have mutations in one or both genes coding for the PCCa and PCCb subunits [1].The deficiency of PCC and the subsequent accumulation of PP-COA lead to the pathogenesis of PA. The most common clinical manifestations of PA include high anion-gap metabolic acidosis, ketonuria and hyperammonemia, which are frequently of sufficient severity to result in neonatal death [3]. Moreover, increased organic acids in the urine, elevated plasma glycine levels, and the characteristic increase in propionylcarnitine (C3) levels are also observed in PA patients. Therefore, detection of the accumulation of propionic acid and other related metabolites forms the basis for the initial screening and examination of patients with suspected PA. In Background: Propionyl coenzyme-A carboxylase (PCC) is a mitochondrial enzyme previously quantifiable only by radiometric assay. Herein, we report a UPLC-MS/MS method as a superior alternative method for assaying PCC's activity. Methodology & Results: For the development of the UPLC-MS/MS method, the mass spectra of propionyl coenzyme-A and methyl malonyl coenzyme-A precursor ions, and their full scan product ions were determined. MRM was used for the quantification of the analytes. The method showed good linearity and selectivity for further bioanalytical study. Conclusion: The developed UPLC-MS/MS method is capable of rapidly quantifying PCC's enzymatic activity and demonstrated suitability for assaying PCC's activity in complex biological samples. Thus, the method will be useful in validating recombinant expression of PCC, and potentially for routine quantification of mitochondrial PCC's activity level in patient cells.

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Investigation of the Drug–Drug Interaction Between α-Lipoic Acid and Valproate via Mitochondrial β-oxidation

Cited by 8 publications

References 23 publications

Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice

Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice

Lipoic acid pharmacokinetics at baseline and 1 year in secondary progressive MS

Development of an UPLC–MS/MS Method for Assaying The Enzymatic Activity of Propionyl Coenzyme-A Carboxylase

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