Oxidative Stress in the Newborn Period: Useful Biomarkers in the Clinical Setting

Abstract

Aerobic metabolism is highly efficient in providing energy for multicellular organisms. However, even under physiological conditions, an incomplete reduction of oxygen produces reactive oxygen species and, subsequently, oxidative stress. Some of these chemical species are highly reactive free radicals capable of causing functional and structural damage to cell components (protein, lipids, or nucleotides). Oxygen is the most used drug in ill-adapted patients during the newborn period. The use of oxygen may cause oxidative stress-related diseases that increase mortality and cause morbidity with adverse long-term outcomes. Conditions such as prematurity or birth asphyxia are frequently treated with oxygen supplementation. Both pathophysiological situations of hypoxia–reoxygenation in asphyxia and hyperoxia in premature infants cause a burst of reactive oxygen species and oxidative stress. Recently developed analytical assays using mass spectrometry have allowed us to determine highly specific biomarkers with minimal samples. The detection of these metabolites will help improve the diagnosis, evolution, and response to therapy in oxidative stress-related conditions during the newborn period.

Oxidative Stress in Preterm Infants: Overview of Current Evidence and Future Prospects

“…The results of these determinations are expressed as ratios, such as the o-Tyr/Phe, m-Tyr/Phe, 3NO2-Tyr/p-Tyr, and 3Cl-Tyr/p-Tyr ratios. These markers have been validated and extensively applied in the clinical setting in various human biofluid matrices, such as amniotic fluid, urine, plasma, cerebrospinal fluid, or human milk in the newborn period [16,24,29,31,36,[61][62][63][64]. In urine, in a pre-clinical study conducted on pig pups, we found a significant increase in both urinary o-tyrosine and 8-oxodG levels after 15 min of hyperoxia by resuscitation [62].…”

“…These are non-enzymatic products from the oxidation of amino acid-free radicals and other PUFAs, and are chemically stable. These compounds have been detected electively in lipid-rich tissues, such as brain tissue, which, being rich in polyunsaturated lipids, is highly sensitive to oxidative stress [ 16 , 17 , 18 , 19 , 20 , 21 , 25 , 29 , 30 , 33 , 34 , 35 , 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 61 , 65 , 66 , 67 ].…”

“…Several amino acid residues can undergo oxidative modifications, including the oxidation of sulfur-containing amino acid residues, the hydroxylation of aromatic groups, the nitration of tyrosine residues, the chlorination of aromatic groups, or the conversion of some amino acid residues to carbonyl derivatives [29]. Proteins are one of the main targets of ROS and RNS damage.…”

“…The oxidation of Phe is due to the attack of the hydroxyl radical (OH), which converts Phe into ortho-tyrosine (o-Tyr) or meta-tyrosine (m-Tyr). Moreover, other byproducts of tyrosine, such as 3-nitrotyrosine (3NO2-Tyr) and 3-chlorothyrosine (3Cl-Tyr), are also useful as biomarkers of nitrosative stress and inflammation, respectively [29]. In the presence of peroxynitrite (ONOO), p-Tyr can be converted into 3NO2-Tyr, a specific biomarker for protein nitration [58].…”

“…Hydroxyl radicals can attack the DNA chain and the nitrogen bases of DNA nucleotides or deoxyribose. The main damage for OS to DNA is generally produced by guanosine-based oxidation products, such as 7,8-hydroxy-2 -deoxyguanosine (8-oxodG or 8-OHdG), which can be measured quantitatively in urine, plasma, and cerebrospinal fluid, among others, by high-performance liquid or gas chromatography coupled with mass spectrometry (UPLC-MS/MS) [29,33,58,59,61,[65][66][67]. Sánchez-Illana et al, have described a method for the simultaneous detection of a panel of oxidative stress-related biomarkers for the quantification of damage to proteins and DNA in human breast milk samples.…”