Oxidative influence on development and differentiation: An overview of a free radical theory of development

Allen, Robert G.; Balin, Arthur K.

doi:10.1016/0891-5849(89)90071-3

Cited by 255 publications

(150 citation statements)

References 210 publications

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“…In contrast, the CDr maintained normal glucose levels when fed HSD or RD [23,24]. Previous in vitro studies demonstrated a higher rate of malformations and growth retardation in embryos of the hyperglycemic CDs rats than in embryos of the streptozotocin-induced diabetic rats when cultured under the same "diabetic environment" [27]. The authors suggested that embryopathy in the Cohen diabetic rat model was induced by a combination of genetic and environmental factors.…”

mentioning

confidence: 83%

The Role of Reactive Oxygen Species in Diabetes‐Induced Anomalies in Embryos of Cohen Diabetic Rats

Zangen

Yaffe

Shechtman

et al. 2002

Journal of Diabetes Research

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The role of the antioxidant defense mechanism in diabetesinduced anomalies was studied in the Cohen diabetes-sensitive (CDs) and -resistant (CDr) rats, a genetic model of nutritionally induced type 2 diabetes mellitus. Embryos, 12.5-day-old, of CDs and CDr rats fed regular diet (RD) or a diabetogenic high-sucrose diet (HSD) were monitored for growth retardation and congenital anomalies. Activity of superoxide dismutase (SOD) and catalaselike enzymes and levels of ascorbic acid (AA), uric acid (UA), and dehydroascorbic acid (DHAA) were measured in embryonic homogenates. When fed RD, CDs rats had a decreased rate of pregnancy, and an increased embryonic resorption. CDs embryos were smaller than CDr embryos; 46% were maldeveloped and 7% exhibited neural tube defects (NTDs). When fed HSD, rate of pregnancy was reduced, resorption rate was greatly increased (56%; P < .001), 47.6% of the embryos were retrieved without heart beats, and 27% exhibited NTD. In contrast, all the CDr embryos were normal when fed RD or HSD. Activity of SOD and catalase was not different in embryos of CDs and CDr rats fed RD. When fed HSD, levels of AA were significantly reduced, the ratio DHAA/AA was significantly increased, and SOD activity was not sufficiently increased when compared to embryos of CDr. The reduced fertility of the CDs rats, the growth retardation, and NTD seem to be genetically determined. Maternal hyperglycemia seems to result in The increased rate of fetal malformations in diabetic pregnancy despite better glycemic control represents a clinical problem and a research challenge. The exact mechanism behind the elevated rate of malformations is presently unknown. It has, however, been suggested that both intrauterine (maternal) environment as well as genetic background may be important [1][2][3][4][5][6][7] in the teratogenic process. As of today, the literature describes 3 main pathways by which diabetes may affect the normal development of the embryos: disturbed inositol uptake, yielding lowered intracellular inositol concentration [8]; diminished flow in the arachidonic acid-prostaglandin pathway, yielding decreased PGE2 concentration [9]; and excess amount of reactive oxygen species, resulting in decreased amount of low-molecular-weight antioxidants, such as vitamin C, uric acid, glutathione, and vitamin E [5,6,10,11]. The reactive oxygen species pathway seems to be the most important pathway because antioxidants may protect against the disturbances of both the inositol and the arachidonic pathways. The proposed mechanisms for increased reactive oxygen species generation at higher glucose concentrations include nonenzymatic protein glycosylation [12][13][14], enhanced mitochondrial electron transport chain flow [15], autooxidation [16], and changes in the redox potential. The relative 247

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mentioning

confidence: 83%

The Role of Reactive Oxygen Species in Diabetes‐Induced Anomalies in Embryos of Cohen Diabetic Rats

Zangen

Yaffe

Shechtman

et al. 2002

Journal of Diabetes Research

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“…This could be due to the marked perturbations in oxidative metabolism and lipid composition during differentiation. Namely, the increased degree of lipid unsaturation demonstrated early during development has been suggested to provide antioxidative protection at the time when antioxidant enzyme defenses are low (31).…”

Section: Discussionmentioning

confidence: 99%

The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

Pejić

Kasapović

Cvetković

et al. 2003

Braz J Med Biol Res

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The sensitivity of copper,zinc (CuZn)-and manganese (Mn)-superoxide dismutase (SOD) to exogenous estradiol benzoate (EB) was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 µg EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%), 8 (72.7%) and 15 (81.7%). In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6%) disappeared on day 8 and on days 15 and 45 it became inhibitory (40.3 and 30.5%, respectively). EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8%) changed to an inhibitory effect on day 8 (38.4%) and disappeared by day 45 when inhibition was detected again (48.7%). In males, the inhibitory effect on this enzyme was observed on days 0 (45.0%) and 15 (28.9%), and then disappeared until day 60 when a stimulatory effect was observed (38.4%). EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process. Correspondence

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“…20 and 21). The activities of enzymic antioxidant defenses tend to be lower in fetal cells than in cells derived from postnatal tissues (22)(23)(24); however, the GSH concentration is frequently greater in fetal cells than in cells from adults (20,24). Whether these observations reflect differences in the steadystate level of ROS in fetal and postnatal cells is not presently known (20,21).…”

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confidence: 93%

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

Allen

Keogh²,

Tresini

et al. 1997

Journal of Biological Chemistry

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We determined the activities of NADH dehydrogenase (ND), succinate dehydrogenase, and cytochrome c oxidase (COX) in 29 skin fibroblast lines established from donors ranging in age from 12 gestational weeks to 94 years. The results of this study demonstrate that all three of the enzyme activities examined are greater in adult-derived fibroblasts than in the fetal cell lines. The ratio of enzyme activities that control electron entry into and exit from the electron transport chain varied directly with lucigenin-detected chemiluminescence (an indicator of ⅐ O 2 ؊ generation) and inversely with H 2 O 2 generation. These results indicate a clear difference in the predominant oxidant species generated during fetal and adult stages of life. We also examined the mRNA abundances of different components of the electron transport chain complexes. We observed higher abundances of mitochondrial encoded mRNAs (COX 1 and ND 4) in cell lines established from adults than in fetal cells. No differences in the mRNA abundances of the nuclear encoded sequences (COX 4 and ND 51) were observed in fetal and postnatal-derived lines. Succinate dehydrogenase mRNA abundance was greater in cell lines established from postnatal donors than in fetal cell lines. No significant differences between cell lines established from young and old adults were detected in any of the parameters examined.Mitochondria are the primary site of aerobic energy production and are thus the major site of generation of reactive oxygen species (ROS), 1 such as oxygen-centered free radicals and peroxides, which are by-products of metabolism (1-4). Estimates of the rate of ROS generation can differ greatly; however, it has been demonstrated repeatedly that the relative rate of oxidant generation increases with age and that this increase correlates strongly with age-associated changes in the cellular redox state (5-8). For example, the rates of superoxide ( ⅐ O 2 Ϫ ) (8 -14) and H 2 O 2 generation (7, 10, 14 -17) increase in the cells of aging organisms, whereas the glutathione concentration declines progressively with advancing age (5,6,18,19). Differences in ROS metabolism also exist between cells obtained from early developmental stages and from postnatal tissues (for review, see Refs. 20 and 21). The activities of enzymic antioxidant defenses tend to be lower in fetal cells than in cells derived from postnatal tissues (22-24); however, the GSH concentration is frequently greater in fetal cells than in cells from adults (20,24). Whether these observations reflect differences in the steadystate level of ROS in fetal and postnatal cells is not presently known (20, 21).The rate of mitochondrial ROS generation in cells is largely dependent on the amounts of autoxidizable respiratory carriers and the redox state of electron carriers (1,3,25,26). All electron carriers located prior to one of low abundance will exhibit a greater propensity to be chemically reduced because of the slowing of electron flux (electron stacking; 1, 16, 25, 27). Thus, either age or development-a...

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Oxidative influence on development and differentiation: An overview of a free radical theory of development

Cited by 255 publications

References 210 publications

The Role of Reactive Oxygen Species in Diabetes‐Induced Anomalies in Embryos of Cohen Diabetic Rats

The Role of Reactive Oxygen Species in Diabetes‐Induced Anomalies in Embryos of Cohen Diabetic Rats

The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

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