Early onset of renal oxidative stress in small for gestational age newborn pigs

Hitesh Soni,Taisiya Yakimkova,Anberitha T Matthews,Paul K Amartey,Robert W Read,Randal K Buddington,Adebowale Adebiyi

doi:10.1080/13510002.2019.1596429

Hitesh Soni, Taisiya Yakimkova + Show 5 more

Open Access

https://doi.org/10.1080/13510002.2019.1596429

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Abstract

ABSTRACTObjective: Oxidative stress, a common feature in cardiovascular and renal disease is associated with the causes and consequences of fetal growth restriction. Hence, renal redox status is likely an early determinant of morbidity in small-for-gestational-age (SGA) infants. In this study, we examined renal oxidative stress in naturally-farrowed SGA newborn pigs.Methods: We studied SGA newborn pigs with 52% less body weight and 59% higher brain/liver weight ratio compared with their appropriate-for-gestational-age (AGA) counterparts.Results: The kidneys of the SGA newborn pigs weighed 56% less than the AGA group. The glomerular cross-sectional area was also smaller in the SGA group. SGA newborn pigs exhibited increased renal lipid peroxidation, reduced kidney and urine total antioxidant capacity, and increased renal nitrotyrosine immunostaining. Whereas the protein expression level of NADPH oxidase (NOX)2 was unchanged, NOX4 expression was significantly higher in SGA kidneys. The level of serum potassium was lower, but serum sodium and creatinine were similar in SGA compared with AGA newborn pigs. The serum concentrations of C‐reactive protein and NGAL, the biomarkers of inflammation and early acute kidney injury were significantly elevated in the SGA group.Conclusion: Early induction of oxidative stress may contribute to the onset of kidney injury in growth-restricted infants.

Highlights

Low birth weight due to premature birth or intrauterine growth restriction (IUGR) is associated with infant and adult cardiovascular, metabolic, and kidney disorders [1,2,3,4]
The weights of the right and left kidneys were ∼54% and 57% less, respectively in SGA compared with AGA newborn pigs (Figure 1(c))
The kidney to body weight ratio was comparable in both groups, indicating that differences in kidney weights were related to body weight variances (Figure 1(d))

Summary

Introduction

Low birth weight due to premature birth or intrauterine growth restriction (IUGR) is associated with infant and adult cardiovascular, metabolic, and kidney disorders [1,2,3,4]. Chronic treatment with the free radical scavenger TEMPOL reversed elevated arterial pressure in male [22], while antioxidant resveratrol promoted recovery from ischemia/reperfusion-induced myocardial injury in both male and female growth-restricted rat offspring [23,24]. These studies indicate that oxidative stress contributes to the etiology and consequences of IUGR. It remains unclear whether basal redox status is altered in naturally-occurring SGA fetal or newborn kidneys

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Conclusion