Perinatal Development of Heart, Kidney, and Liver Mitochondrial Antioxidant Defense

Abstract

ABSTRACT. Development of the mitochondrial antioxidant defense system was studied to assess its potential role in the newborn mammal's tolerance to oxidative challenge and to gain insight into the fetal adaptation to a relatively hyperoxic adult environment. Isolated heart, kidney, and liver mitochondria from fetal, newborn, and adult guinea pigs were used. In situ function of the antioxidant enzymes was estimated in mitochondrial suspensions after the addition to selenite or tert-butyl hydroperoxide by determining NAD(P)H oxidation rates spectrophotometrically at 340-375 nm. Kidney and liver mitochondria from newborn animals were less susceptible to selenite and tert-butyl hydroperoxide-induced NAD(P)H oxidation. The pattern of change, however, varied widely with tissue type. Kidney mitochondria displayed the largest change with a 3-to 4-fold increase in rate from the fetal to adult period. NAD(P)H oxidation rates in intact mitochondria did not correlate consistently with glutathione reductase and peroxidase activities in sonicated mitochondria suggesting in situ regulation by other endogenous factors. Immediately after birth, mitochondrial glutathione reductase and peroxidase activities dropped 38-50% and 50-70%, respectively, in all tissues studied. Total glutathione content of heart and liver mitochondria did not change with age. Adult kidney mitochondrial glutathione, however, declined to 24% of fetal values. Mitochondrial superoxide dismutase activity increased 150-300% from the fetal to the adult period in all tissues studied. Perinatal changes in the mitochondrial antioxidant system and their relationship to mitochondrial calcium metabolism are discussed in terms of the newborn's resistance to oxidative stress. (Pediatr Res 26:220-226, 1989) Abbreviations GSH, reduced glutathione GSSG, oxidized glutathione SOD, manganese superoxide dismutase tBOOH, tert-butyl hydroperoxide Mammalian birth introduces a dramatic environmental change on the emerging organism. Altered circulation and oxygen availability necessitate adaptive changes in metabolism. Before birth, fetal oxygen tensions (Pao2) are low (25 mm Hg). After birth, average Pao2 rises (to 80-90 mm Hg) initiating the switch to a more aerobic metabolism (1-4). In the newborn

Developmental differences in the immortalization of lung fibroblasts by telomerase

“…Vlessis & Mela-Riker, 1989;Sohal et al ., 1990). One study compared two fetal lung fibroblasts (WI-38 and MRC-5) with five different neonatal-adult skin fibroblasts and found both fetal lung strains to have lower levels of oxidant defences and altered levels of a variety of factors (Serra et al ., 2003).…”

Evidence of Oxidative Stress in Full-Term Healthy Infants

“…The evolutionary adaptation to extra uterine aerobic existence required the development of efficient cellular electron transport systems to produce energy. In concert with this challenge to energyproducing oxidative metabolism, biochemical defenses including antioxidant enzymes, evolved to protect against oxidation of cellular constituents by oxygen radicals (3)(4)(5).…”

The importance of oxygen free radicals in the neonatal period

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