Correlation between plasma 5-aminolevulinic acid concentrations and indicators of oxidative stress in lead-exposed workers

Abstract 5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria and lead poisoning, undergoes metal-catalyzed aerobic oxidation at physiological pH to yield reactive free radical species (O2−·>, HO·, and ALA·). We analyzed the relationships between plasma ALA concentrations, blood concentrations of lead, protoporphyrin IX (PP-IX), superoxide dismutase (SOD), and methemoglobin (metHb), and urine chemiluminescence (CL) in samples collected from lead-exposed workers. All variables measured were substantially (P <0.01) higher (2–8-fold) in the lead-exposed workers (n = 60). Plasma ALA concentrations were, on average, 6-fold higher in lead-exposed workers. We observed positive linear relationships between ALA and lead (r = 0.992), ALA and PP-IX (r = 0.891), ALA and metHb (r = 0.984), lead and SOD (r = 0.948), ALA and urine CL (r = 0.987), and lead and PP-IX (r = 0.993). These data are consistent with our free radical hypothesis for lead poisoning, where ALA distribution to and accumulation in several organs may trigger oxidative stress responses.

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Damage to rat liver mitochondria promoted by δ-aminolevulinic acid-generated reactive oxygen species: connections with acute intermittent porphyria and lead-poisoning

Biochimica et Biophysica Acta (BBA) - Bioenergetics ◽

10.1016/s0005-2728(05)80072-6 ◽

1991 ◽

Vol 1056 (1) ◽

pp. 57-63 ◽

Cited By ~ 105

Author(s):

Marcelo Hermes-Lima ◽

Valderez G.R. Valle ◽

Anibal E. Vercesi ◽

Etelvino J.H. Bechara

Keyword(s):

Reactive Oxygen Species ◽

Rat Liver ◽

Lead Poisoning ◽

Aminolevulinic Acid ◽

Reactive Oxygen ◽

Acute Intermittent Porphyria ◽

Liver Mitochondria ◽

Rat Liver Mitochondria ◽

Oxygen Species

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Hematin administration to an adult with lead intoxication

Blood ◽

10.1182/blood.v53.5.1007.bloodjournal5351007 ◽

1979 ◽

Vol 53 (5) ◽

pp. 1007-1011

Author(s):

JM Lamon ◽

BC Frykholm ◽

DP Tschudy

Keyword(s):

Lead Poisoning ◽

Aminolevulinic Acid ◽

Acute Intermittent Porphyria ◽

Lead Intoxication ◽

Neurologic Manifestations ◽

Heme Metabolism ◽

Urinary Ala

Lead poisoning and acute intermittent porphyria (AIP) may exhibit similar neurologic manifestations, and they have in common elevated excretion of urinary aminolevulinic acid (ALA). Despite their similarities, the possible pathophysiologic connection between AIP and lead poisoning in not known. Because intravenous hematin administration has produced biochemical improvement in AIP, a hematin trial in lead intoxication was of interest with respect to some of the heme metabolism abnormalities observed in the condition. Significant diminution of urinary ALA and coproporphyrin excretion occurred in association with intravenous hematin administration.

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Abstract P198: Redox Monitoring Reveals Increased Susceptibility of Whole Blood to Oxidative Stress During Hemorrhagic Shock

Circulation ◽

10.1161/circ.118.suppl_18.s_1488-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Nathan J White ◽

Maryanne M Collinson ◽

Richard A Boe ◽

Kevin R Ward

Keyword(s):

Oxidative Stress ◽

Free Radical ◽

Redox Potential ◽

Stress Responses ◽

Whole Blood ◽

P Value ◽

Redox Potentials ◽

Redox Stress ◽

Voltage Potential ◽

Severe Shock

Introduction: The oxidation/reduction (redox) chemistry of blood during resuscitation is not well defined. Improved understanding of whole blood redox behavior would assist in developing better resuscitation monitoring and possibly reducing free radical injury both of which are PULSE initiative priorities. We use direct electrochemical measurement of equilibrium redox potential to assess the hypothesis that the overall response of blood to strong oxidant/reductant challenge is altered during shock. Methods: Five swine underwent hemorrhage to an oxygen debt (OD) of 80 cc/kg. Arterial blood was tested at baseline (BL) and after hemorrhage when OD equaled 40 and 80 cc/kg. Native redox potential was measured as the equilibrium voltage potential recorded between a freshly polished 2mm Au and standard Ag/AgCl electrode submerged in whole blood (n=34). The oxidative and reductive stress responses at each level of OD were defined as the change from native voltage potential induced by the addition of a strong oxidant (KMnO4) (n=18) or reductant (Dithiotreitol) (n=18). Mean native redox potentials and mean redox stress responses were compared for differences at increasing levels of OD using repeated measures ANCOVA. Results: Lactate increased significantly with OD (mean diff BL vs. OD=80, +4.7 mmol/L [1.3, 8.1]). No effect of OD was found on native redox potential (p value =0.233). A significant effect of OD was found on redox stress response (p value =0.0276). The redox response to oxidative stress increased from BL with increasing oxygen debt, and became significantly greater at OD=80 cc/kg (mean diff =+31.9 Rmv [3.9, 59.9]). Conclusions: Whole-blood redox potential did not change significantly even with severe shock, suggesting active redox buffering. However, our results suggest that the oxidative buffering capacity of blood may become impaired during severe shock as demonstrated by the significantly more positive redox potentials elicited by oxidative stress when OD was elevated. Impaired redox buffering during shock may exacerbate free radical injury induced by the oxidative stress of resuscitation. Monitoring the response of blood to oxidative stress may be a useful way to determine susceptibility to oxidative damage during resuscitation.

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Antioxidant Effect of Melatonin in Preterm Newborns

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6308255 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Lucia Marseglia ◽

Eloisa Gitto ◽

Elisa Laschi ◽

Maurizio Giordano ◽

Carmelo Romeo ◽

...

Keyword(s):

Oxidative Stress ◽

Placebo Group ◽

Free Radical ◽

Preterm Infants ◽

Plasma Concentrations ◽

Preterm Neonates ◽

Double Blind ◽

Blood Concentrations ◽

Melatonin Administration ◽

Preterm Newborns

Introduction. Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. Objective. The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. Methods. A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. Results. At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group ( 52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group ( 36.48 ± 33.85 pg/mL vs. 89.97 ± 52.01 pg/mL). Conclusions. Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

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Correlation between clinical indicators of lead poisoning and oxidative stress parameters in controls and lead-exposed workers

Toxicology ◽

10.1016/j.tox.2003.09.009 ◽

2004 ◽

Vol 195 (2-3) ◽

pp. 147-154 ◽

Cited By ~ 180

Author(s):

Hande Gurer-Orhan ◽

Handan U Sabır ◽

Hilal Özgüneş

Keyword(s):

Oxidative Stress ◽

Lead Poisoning ◽

Clinical Indicators ◽

Oxidative Stress Parameters ◽

Exposed Workers ◽

And Oxidative Stress ◽

Stress Parameters

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Hematin administration to an adult with lead intoxication

Blood ◽

10.1182/blood.v53.5.1007.1007 ◽

1979 ◽

Vol 53 (5) ◽

pp. 1007-1011 ◽

Cited By ~ 13

Author(s):

JM Lamon ◽

BC Frykholm ◽

DP Tschudy

Keyword(s):

Lead Poisoning ◽

Aminolevulinic Acid ◽

Acute Intermittent Porphyria ◽

Lead Intoxication ◽

Neurologic Manifestations ◽

Heme Metabolism ◽

Urinary Ala

Abstract Lead poisoning and acute intermittent porphyria (AIP) may exhibit similar neurologic manifestations, and they have in common elevated excretion of urinary aminolevulinic acid (ALA). Despite their similarities, the possible pathophysiologic connection between AIP and lead poisoning in not known. Because intravenous hematin administration has produced biochemical improvement in AIP, a hematin trial in lead intoxication was of interest with respect to some of the heme metabolism abnormalities observed in the condition. Significant diminution of urinary ALA and coproporphyrin excretion occurred in association with intravenous hematin administration.

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