Biological Rancidification

Dormandy, T. L.

doi:10.1016/s0140-6736(69)90390-0

Cited by 59 publications

(25 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recognizing that there are intrinsic developmental mechanisms that protect the lung against oxidant injury (6,8), we have tested the hypothesis that, by targeting the maturation of the lipofibroblast, we could protect the lung against oxidant injury. To that end, we observed that antenatal administration of RGZ-enhanced fetal lung maturation and virtually blocked 24-h hyperoxia-induced lung molecular and morphometric changes postnatally, suggesting a novel antenatal intervention to protect against hyperoxia-induced neonatal lung injury.…”

Section: Discussionmentioning

confidence: 99%

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Rehan

Sakurai

Corral

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The physiological development and homeostasis of the lung alveolus is determined by the expression of peroxisome proliferator-activated receptor-␥ (PPAR-␥) by the interstitial lipofibroblast. We have recently shown (Dasgupta C et al., Am J Physiol Lung Cell Mol Physiol 296: L1031-L1041, 2009.) that PPAR-␥ agonists administered postnatally accelerate lung maturation and prevent hyperoxia-induced lung injury. However, whether the same occurs antenatally is not known. The objective of this study was to test the hypothesis that the potent PPAR-␥ agonist rosiglitazone (RGZ), administered antenatally, enhances fetal lung maturation and protects against hyperoxia-induced neonatal lung injury. Sprague-Dawley rat dams were administered either diluent or RGZ (3 mg/kg), at late gestation, to determine its effect on lung maturation and on hyperoxia (95% O 2 exposure for 24 h)-induced neonatal lung injury. The lungs were examined for the expression of specific markers of alveolar development (surfactant proteins A and B, cholinephosphate cytidylyltransferase-␣, leptin receptor, triglyceride uptake, and [ 3 H]choline incorporation into saturated phosphatidylcholine) and injury/repair, in particular, the markers of transforming growth factor-␤ signaling (activin receptor-like kinase-5, SMAD3, lymphoid enhancer factor-1, fibronectin, and calponin). Overall, antenatal RGZ accelerated lung maturation and blocked the inhibition of alveolar sacculation and septal wall thinning by hyperoxia. RGZ specifically stimulated the development of the alveolar epithelial type II cell, the lipofibroblast, and the vasculature. The increased expression of the transforming growth factor-␤ intermediates, such as SMAD3 and lymphoid enhancer factor-1, implicated in hyperoxic lung injury, was also blocked by antenatal RGZ treatment. In conclusion, PPAR-␥ agonists can enhance fetal lung maturation and can effectively prevent hyperoxia-induced neonatal lung injury. lung development; peroxisome proliferator-activated receptor-␥; surfactant; lipofibroblast; hyperoxia SEVERAL LINES OF EVIDENCE suggest that lipids are cytoprotective against oxygen free radical lung injury in vitro and in vivo (5,23,37). Investigators have suggested that the greater oxygen tolerance of newborn rats and mice, compared with their adult counterparts, relates, in part, to the greater amount of triglyceride in the lipid fraction of the newborn compared with the adult lung (14,24,25,37). Feeding pregnant rats a high triglyceride diet results in increased triglyceride content in the lungs of their offspring, increased survival, and improved pathological status after prolonged hyperoxic exposure (25). In contrast, newborn offspring of rats fed low-polyunsaturated fatty acid diets are more susceptible to pulmonary oxygen toxicity and early lethality in hyperoxia (24). Furthermore, Kehrer and Autor (14) demonstrated that increasing the saturated fatty acid composition of lung triglycerides in adult rats by dietary manipulation produced increased susceptibility to oxygen toxicity.Ou...

show abstract

Section: Discussionmentioning

confidence: 99%

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Rehan

Sakurai

Corral

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…In addition, in our previous studies, we found a similar degree of protection against pulmonary 0 2 toxicity in newborn offspring of rat dams fed either a safflower oil-based or fish oil-based high-PUFA diet, even though the safflower diet pups demonstrated surfactant, and lung eicosanoids might be playing in the hyperoxic protection of Intralipid offspring, results of our present (and previous) studies suggest that the increased PUFA content in lung tissue itself may, at least in part, be an explanation for the consistently observed increased oxygen tolerance in our neonatal rats. Dormandy (26) has proposed, in a theory diametrically o~~o s i t e to traditional biochemical theorv. that intracellular PUFA, located in noncritical, nonmembrahk sites, could serve to avidly scavenge excess 0 2 free radicals and thereby prevent their toxic interaction with critical membrane PUFA, thus protecting cells from hyperoxic or O2 free radical-mediated damage.…”

Section: Discussionmentioning

confidence: 99%

Intralipid Increases Lung Polyunsaturated Fatty Acids and Protects Newborn Rats from Oxygen Toxicity

1991

View full text Add to dashboard Cite

ABSTRACT. Intralipid, derived from soybean oil and con-6-keto-PGF,-a, 6-keto-prostaglandin FI-a taining a high percentage of n-6 family polyunsaturated LTC4-F4, leukotrienes C4-F4 fatty acids (PUFA) and also linolenic acid, an n-3 family BPD, bronchopulmonary dysplasia PUFA, is commonly the first fat source provided to very P/S, polyunsaturated/saturated fatty acid ratio low birth weight premature infants. Following up on our previous reports that newborn rats born to dams fed high-PUFA diets demonstrate superior tolerance to hyperoxia, we examined whether the high-PUFA fat source Intralipid might also protect against oxygen toxicity. Adult female With the progression of modern neonatal intensive care, rats were fed either regular Rat Chow or fat-free diet greater numbers of VLBW oxygen-and ventilator-requiring precontaining 20%-Intralipid as the fat source for 3 wk before mature infants are surviving. However, despite favorable outand then throughout pregnancy and lactation. One-and 5-comes in terms of mortality, these infants are at extremely high d-old offspring of Intralipid diet-fed dams demonstrated risk of developing the chronic lung process known as BPD, significant increases in lung lipid n-6 family PUFA plus considered to be related, at least in part, to the damaging effect elevated linolenic acid compared with regular diet-fed off-of oxygen on the lung (1). Because of the overwhelming clinical spring. These characteristic fatty acid patterns, apparent problems that these VLBW premature infants experience in the in total lung lipids, were even more pronounced in the first several days of life, nutritional needs are frequently not the triglyceride fraction compared with the phospholipid frac-highest priority in their care. In fact, common nursery practices tion. Associated with these fatty acid changes were signif-consist of a several-day interval between the birth of a VLBW icantly improved hyperoxic survival rates (89 out of oxygen-requiring premature infant and the initial administration 95 = 94% survival after 7 d of >95% O2 exposure) in of lipid nutrition. Because of the vulnerability of the VLBW Intralipid offspring (versus 89 out of 106 = 84%, p < 0.05 premature infant to the effects of a delay in lipid nutrition (2) in regular diet offspring) and evidence of superior clinical/ and the possible role that lipids might play in protecting the lung pathologic status. No differences in pulmonary antioxidant from oxygen toxicity, the early withholding of lipid nutrition enzyme or surfactant system development, response of from these critically ill neonates might increase their risk of antioxidant enzymes to hyperoxic exposure, or lung pros-developing the chronic lung disease and damage of BPD. taglandin EZ, 6-keto PGFI-a or leukotrienes C4-F, were Evidence is available from the literature to suggest that lung present. These findings continue to support the hypothesis lipid composition is related to hyperoxic tolerance and protection that increasing lung PUFA content may provide increased against hypero...

show abstract

“…Oxidation of sulfhydryl groups (20,22)-, microsomes, mitochondria (24)(25)(26)(27), and swelling and lysis of mitochondria (27) have been reported secondary to lipid peroxidation. Indeed free radical formation has been incriminated as one of the mechanisms responsible for the process of aging (28,29).…”

Section: In Vitro Incubation Of Heavy Plateletsmentioning

confidence: 99%

Heterogeneity of human platelets

Karpatkin¹,

Strick²

1972

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Human platelets were separated by density-centrifugation into heavy and light populations. Heavy platelets have an average volume approximately twofold greater than light platelets, and have previously been shown to be young platelets.All 11 enzymes of the Embden-Meyerhof pathway plus the five related enzymes: phosphoglucomutase, glucose-6-P dehydrogenase, 6-P-gluconic dehydrogenase, a-glycerol-P dehydrogenase, and glutathione reductase (TPNH) were examined in cell lysates from total, heavy, and light platelet populations. Apparent Km for individual enzymes were measured in a total platelet population. Empirical Vm.. of the individual enzymes were measured in total, heavy, and light platelet populations. The three apparent rate-limiting enzymes for glycolysis were hexokinase, phosphofructokinase, and glyceraldehyde-3-P dehydrogenase.Heavy platelets contained approximately twofold greater enzyme activity (per gram wet weight) than light platelets for 7 of the 16 enzymes measured: hexokinase, phosphohexoisomerase, phosphofructokinase, glyceraldehyde-3-P dehydrogenase, phosphoglycerokinase, lactic dehydrogenase, and phosphoglucomutase.

show abstract

Biological Rancidification

Cited by 59 publications

References 29 publications

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Antenatally administered PPAR-γ agonist rosiglitazone prevents hyperoxia-induced neonatal rat lung injury

Intralipid Increases Lung Polyunsaturated Fatty Acids and Protects Newborn Rats from Oxygen Toxicity

Heterogeneity of human platelets

Contact Info

Product

Resources

About