[13C]Methionine breath test: a novel method to detect antiretroviral drug-related mitochondrial toxicity

Milazzo, Laura; Piazza, Manuela; Sangaletti, O.; Gatti, Nadia; Cappelletti, Anna; Adorni, Fulvio; Antinori, Spinello; Galli, Massimo; Moroni, Mauro; Riva, Agostino

doi:10.1093/jac/dkh497

Cited by 37 publications

(29 citation statements)

References 28 publications

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“…Methionine transamination is another potential pathway of methionine catabolism that results in the conversion of the methyl or carboxyl carbon to CO 2 and occurs primarily in the liver. However, this pathway does not occur under normal metabolic conditions in mammals (18,24).Each of the pathways, as noted earlier, produces CO 2 in the intermediary metabolism of methionine. By relying on the pathways of methionine degradation to CO 2 , previous studies suggest that a 13 C-labeled methionine ([ 13 C]-Met) breath test ([ 13 C]-MBT) could be used to evaluate the methionine oxidative capacity of the liver (9).…”

mentioning

confidence: 87%

900 13C-Methionine Breath Test to Assess Intestinal Failure Associated Liver Disease

Duro¹,

Fitzgibbons²,

Valim³

et al. 2009

Gastroenterology

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Oxidation of L[1-13 C]methionine ([ 13 C]-Met) in liver mitochondria can be quantified by measuring exhaled 13 CO 2 . We hypothesized that 13 CO 2 recovery after i.v. administered [ 13 C]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-13 C]-Met breath tests ([ 13 C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [ 13 C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for 13 CO 2 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO 2 ) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mo) underwent a total of 34 [ 13 C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The Intestinal failure (IF) is a clinical condition in which the body is incapable of supporting growth and/or fluid and electrolyte homeostasis because of inadequate functional intestinal surface area. In the neonatal population, recent reports estimate an incidence of up to 0.7% in very low birth weight infants, and up to 1.1% in extremely low birth weight infants. The associated mortality of IF in very low birth weight infants is thought to be as high as 20% (1).The mainstay of modern medical therapy for IF is parenteral nutrition (PN), but unfortunately, this therapy can be accompanied by liver injury that is termed intestinal failure-associated liver disease (IFALD). The etiology of IFALD can be multifactorial, and beyond its association with PN, IFALD has been linked with prematurity, number of infectious episodes, ability to tolerate enteral nutrition, number of laparotomies, number of days on antibiotics, and other yet to be identified factors (2). Although liver biopsy remains the gold standard for the evaluation of IFALD, the invasive nature of this test precludes its use as a frequent measure of disease progression or recovery. Conventional static biochemical liver tests (transaminase, bilirubin, alkaline phosphatase and albumin plasma levels, or prothrombin time) have been used to assess injury and function but vary widely in specificity and sensitivity (7-9). For example, patients with IFALD with normal or mildly elevated bilirubin can often have cirrhosis as determined by liver biopsy (10).In recognition of these deficiencies, the Child-Turcotte and Pugh (CTP) scoring system was initially developed in 1964 to assess the severity of chronic liver disease (11) and more recently, another widely used scoring system, the model for end-stage liver disease (MELD), was developed using serum creatinine, international normalized ratio (INR), and bilirubin to predict survival in adult patients with chronic liver disease (12). The pediatric end-stage liver disease (PELD) score is similar ...

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mentioning

confidence: 87%

900 13C-Methionine Breath Test to Assess Intestinal Failure Associated Liver Disease

Duro¹,

Fitzgibbons²,

Valim³

et al. 2009

Gastroenterology

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“…Rather than inferring metabolism paths from detailed genetic testing, the patient is given a benign surrogate that is isotopically labeled, and then, the metabolism pathway is directly monitored via an exhaled gas, typically 13 C-labeled CO 2 (Modak 2007). For example, cancer patients are treated with 13 C-labeled methionine to assess mitochondrial toxicity of antiretroviral drugs (Milazzo et al 2005), or with [ 13 C]-dextromethorphan to assess breast cancer therapy with tamoxifen (Opdam et al 2015 …”

Section: Isotopically Labeled Tracer Compoundsmentioning

confidence: 99%

Breath biomarkers in toxicology

Pleil

2016

Arch Toxicol

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“…[76][77][78] Flow cytometric techniques employ a cationic lipophilic fluorochrome with an affinity for mitochondria with high membrane potential. This method has the added advantage that circulating leukocyte subsets are easily separated and compared.…”

Section: Research History Of Nucleoside Reverse Transcriptase Inhibitmentioning

confidence: 99%

“…The authors concluded that hepatic mitochondrial dysfunction is drug related as opposed to HIV related and that the 13 C methionine breath test is superior to lactate measurement for detection of subclinical toxicity. 77 Paediatric HIV presents additional scenarios where children who do not contract HIV are exposed to ART, either in utero during maternal treatment, or perinatally during prevention of mother to child transmission (PMTCT) of HIV. In addition, most HIV-infected children are not ART naïve prior to initiation of therapy, and clinical mitochondrial dysfunction has been described in over 30% of perinatally infected children followed up longitudinally.…”

Section: Research History Of Nucleoside Reverse Transcriptase Inhibitmentioning

confidence: 99%

Mitochondrial dysfunction and human immunodeficiency virus infection

Watt

2011

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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Human immunodeficiency virus (HIV) infection and the pharmacological treatment thereof have both been shown to affect mitochondrial function in a number of tissues, and each may cause specific organ pathology through specific mitochondrial pathways. HIV has been shown to kill various tissue cells by activation of mitochondrial apoptosis. Nucleoside analogues, used extensively to treat HIV infection, are known to influence a number of steps affecting mitochondrial DNA integrity. This review describes the basic physiology, pharmacology and pathophysiology of HIV infection and the nucleoside analogues regarding mitochondrial function and discusses the progress made in this field with respect to the measurement of these effects and the prediction of potential drug toxicity.Peer reviewed.

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[13C]Methionine breath test: a novel method to detect antiretroviral drug-related mitochondrial toxicity

Cited by 37 publications

References 28 publications

900 13C-Methionine Breath Test to Assess Intestinal Failure Associated Liver Disease

900 13C-Methionine Breath Test to Assess Intestinal Failure Associated Liver Disease

Breath biomarkers in toxicology

Mitochondrial dysfunction and human immunodeficiency virus infection

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