Urinary Thiobarbituric Acid–Reacting Substances as Potential Biomarkers of Intrauterine Hypoxia

Siciarz, Ann; Weinberger, Barry; Witz, Gisela; Hiatt, Mark; Hegyi, Thomas

doi:10.1001/archpedi.155.6.718

Cited by 23 publications

(14 citation statements)

References 22 publications

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“…Furthermore, urinary MDA levels exhibited a significant correlation with serum MDA levels in these infants. Elevated urinary MDA levels have been reported earlier in term infants with acute asphyxia [3] . However, these authors failed to find any correlation between urinary MDA and DRR.…”

Section: Discussionmentioning

confidence: 61%

“…Free radicals can produce cellular injury by lipid peroxidation which can be assessed by measuring malondialdehyde (MDA) levels in biological specimens [2] . Some of the newborns requiring resuscitation at birth may subsequently develop hypoxic ischemic encephalopathy (HIE) wherein free radicals have been implicated as mediators of tissue injury [3] . The objective of this study was therefore to investigate whether urinary MDA levels are elevated in newborns following DRR.…”

Section: Introductionmentioning

confidence: 99%

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Urinary Malondialdehyde Levels in Newborns following Delivery Room Resuscitation

Kumar

Panigrahi²,

Basu³

et al. 2008

Neonatology

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Background: Delivery room resuscitation (DRR) is a common emergency in newborns, particularly in resource-poor settings where intrapartum monitoring is not readily available. It may give rise to oxidative stress in neonates due to reoxygenation and reperfusion of previously hypoxic and ischemic tissues. Urinary malondialdehyde (MDA), being non-invasive, may serve as a marker of oxidative stress in these infants. Objective: We assessed oxidative stress in term newborns requiring DRR by measuring MDA levels in urine and serum samples collected at 12–24 h of age. Methods: The study population consisted of 41 cases and 63 healthy age-matched control infants. The inclusion criterion was a need for positive pressure ventilation at birth for >1 min. MDA levels were measured colorimetrically by thiobarbituric acid reaction. Results: Urinary and serum MDA levels were found to be significantly higher in cases than in controls. Of the neonates given DRR, urinary and serum MDA values were elevated in those infants who passed meconium in utero, developed hypoxic ischemic encephalopathy or expired than in those who did not have these complications, but the difference was not significant. We found a significant correlation between urinary and serum MDA levels in infants given DRR. Conclusion: Newborns requiring DRR are subjected to significant oxidative stress which can be easily assessed by measuring urinary MDA levels.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Urinary Malondialdehyde Levels in Newborns following Delivery Room Resuscitation

Kumar

Panigrahi²,

Basu³

et al. 2008

Neonatology

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“…Unlike xanthine dehydrogenase, XO generates hydrogen peroxide as a byproduct of purine degradation 4, 6 . This hydrogen peroxide in combination with other reactive oxygen species (ROS) produced during hypoxia, oxidizes uric acid to form allantoin and reacts with lipid membranes to generate malondialdehyde (MDA) [7][8][9] …”

mentioning

confidence: 99%

Biochemical Measurement of Neonatal Hypoxia

Plank

Calderon

Asmerom

et al. 2011

JoVE

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Neonatal hypoxia ischemia is characterized by inadequate blood perfusion of a tissue or a systemic lack of oxygen. This condition is thought to cause/exacerbate well documented neonatal disorders including neurological impairment 1-3 . Decreased adenosine triphosphate production occurs due to a lack of oxidative phosphorylation. To compensate for this energy deprived state molecules containing high energy phosphate bonds are degraded 2 . This leads to increased levels of adenosine which is subsequently degraded to inosine, hypoxanthine, xanthine, and finally to uric acid. The final two steps in this degradation process are performed by xanthine oxidoreductase. This enzyme exists in the form of xanthine dehydrogenase under normoxic conditions but is converted to xanthine oxidase (XO) under hypoxia-reperfusion circumstances 4, 5 . Unlike xanthine dehydrogenase, XO generates hydrogen peroxide as a byproduct of purine degradation 4, 6 . This hydrogen peroxide in combination with other reactive oxygen species (ROS) produced during hypoxia, oxidizes uric acid to form allantoin and reacts with lipid membranes to generate malondialdehyde (MDA) [7][8][9] . Most mammals, humans exempted, possess the enzyme uricase, which converts uric acid to allantoin. In humans, however, allantoin can only be formed by ROS-mediated oxidation of uric acid. Because of this, allantoin is considered to be a marker of oxidative stress in humans, but not in the mammals that have uricase.We describe methods employing high pressure liquid chromatography (HPLC) and gas chromatography mass spectrometry (GCMS) to measure biochemical markers of neonatal hypoxia ischemia. Human blood is used for most tests. Animal blood may also be used while recognizing the potential for uricase-generated allantoin. Purine metabolites were linked to hypoxia as early as 1963 and the reliability of hypoxanthine, xanthine, and uric acid as biochemical indicators of neonatal hypoxia was validated by several investigators [10][11][12][13] . The HPLC method used for the quantification of purine compounds is fast, reliable, and reproducible. The GC/MS method used for the quantification of allantoin, a relatively new marker of oxidative stress, was adapted from Gruber et al 7 . This method avoids certain artifacts and requires low volumes of sample. Methods used for synthesis of MMDA were described elsewhere 14,15 . GC/MS based quantification of MDA was adapted from Paroni et al. and Cighetti et al. 16,17 . Xanthine oxidase activity was measured by HPLC by quantifying the conversion of pterin to isoxanthopterin 18 . This approach proved to be sufficiently sensitive and reproducible.

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“…After incubation at 100 °C, the absorbance of samples at 532 nm was measured and calculated using the molar extinction coefficient and expressed as mM/mM creatinine (19). The protein oxidation level was monitored by a spectrophotometric determination of carbonyl content by the method of Levine using 2,4-dinitrophenylhydrazine (DNPH) as a classic carbonyl reagent (20).…”

Section: Methodsmentioning

confidence: 99%

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

Cvetković¹,

Vlahović²,

Đorđević³

et al. 2008

Journal of Medical Biochemistry

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The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.

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Urinary Thiobarbituric Acid–Reacting Substances as Potential Biomarkers of Intrauterine Hypoxia

Cited by 23 publications

References 22 publications

Urinary Malondialdehyde Levels in Newborns following Delivery Room Resuscitation

Urinary Malondialdehyde Levels in Newborns following Delivery Room Resuscitation

Biochemical Measurement of Neonatal Hypoxia

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

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