scholarly journals Effects of Low-Dose versus High-Doseγ-Tocotrienol on the Bone Cells Exposed to the Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Nizar Abd Manan ◽  
Norazlina Mohamed ◽  
Ahmad Nazrun Shuid

Oxidative stress and apoptosis can disrupt the bone formation activity of osteoblasts which can lead to osteoporosis. This study was conducted to investigate the effects ofγ-tocotrienol on lipid peroxidation, antioxidant enzymes activities, and apoptosis of osteoblast exposed to hydrogen peroxide (H2O2). Osteoblasts were treated with 1, 10, and 100 μM ofγ-tocotrienol for 24 hours before being exposed to 490 μM (IC50) H2O2for 2 hours. Results showed thatγ-tocotrienol prevented the malondialdehyde (MDA) elevation induced by H2O2in a dose-dependent manner. As for the antioxidant enzymes assays, all doses ofγ-tocotrienol were able to prevent the reduction in SOD and CAT activities, but only the dose of 1 μM of GTT was able to prevent the reduction in GPx. As for the apoptosis assays,γ-tocotrienol was able to reduce apoptosis at the dose of 1 and 10 μM. However, the dose of 100 μM ofγ-tocotrienol induced an even higher apoptosis than H2O2. In conclusion, low doses ofγ-tocotrienol offered protection for osteoblasts against H2O2toxicity, but itself caused toxicity at the high doses.

2021 ◽  
Author(s):  
Johnmark Ndinawe ◽  
Hellen W. Kinyi

Abstract ObjectiveAmaranths leaves are rich in ascorbic acid and polyphenol compounds which have antioxidant activity. The aim of this study was to evaluate their in vivo antioxidant activity. The effect of consumption of Amaranth leaf extract on in vivo antioxidant activity, catalase enzyme activity and H2O2 induced oxidative stress in Drosophila melanogaster flies was assessed.ResultsConsumption of Amaranth leaf extract was associated with increased survival on exposure to H202 in a dose dependent manner in Drosophila melanogaster flies.


Development ◽  
1997 ◽  
Vol 124 (12) ◽  
pp. 2477-2488 ◽  
Author(s):  
A.K. Knecht ◽  
R.M. Harland

We have investigated mechanisms of dorsal-ventral patterning of neural tissue, using Xenopus ectoderm neuralized by noggin protein. This tissue appears to be patterned dorsoventrally; cp1-1, a gene expressed in the dorsal brain, and etr-1, a gene largely excluded from the dorsal brain, are expressed in separate territories in noggin-treated explants (Knecht, A. K., Good, P. J., Dawid, I. B. and Harland, R. M. (1995) Development 121, 1927–1936). Here we show further evidence that this pattern represents a partial dorsal-ventral organization. Additionally, we test two mechanisms that could account for this pattern: a dose-dependent response to a gradient of noggin protein within the explant, and regulative cell-cell interactions. We show that noggin exhibits concentration-dependent effects, inducing cp1-1 at low doses but repressing it at high doses. Since noggin acts by antagonizing Bone Morphogenetic Protein (BMP) signaling, this result suggests that BMPs also may act in a dose-dependent manner in vivo. However, in the absence of a noggin gradient, regulative cell-cell interactions can also pattern the tissue. Such regulation is facilitated by increased motility of noggin-treated cells. Finally, the response of cells to both of these patterning mechanisms is ultimately controlled by a third process, the changing competence of the responding tissue.


2019 ◽  
Vol 7 (2) ◽  
pp. 35
Author(s):  
Nermeen Borai El-Borai ◽  
Seham Said Hadad ◽  
Hanem Kamal Khalifa

Extensive use of imidacloprid (IMI) insecticide in the agro-vet practices leads to continuous animal and human exposure. Exposure of pregnant dams to such insecticides results in fetal malformations. In the light of this, the present study was designed to investigate the teratogenic effects of two different doses of IMI and the possible mechanistic role of oxidative stress. Fifteen pregnant females were randomly divided into three equal groups and orally treated daily during organogenesis period (6-15th GD), control (distilled water), LD-IMI (45 mg/kg) and HD-IMI (90 mg/kg). All pregnant dams were exposed to caesarean section on GD 20. Exposure to IMI induced significant increase in the percentage of resorptions at high-dose with significant reduction of fetal and placental weights in a dose-dependent manner. External fetal morphological abnormalities were recorded only at high-dose while several visceral abnormalities were observed in fetuses at low- and high-doses. Significant increases in the percentages of fetal skeletal malformations were recorded only in the high-dose group. Significant changes in MDA, GSH levels and CAT activity with insignificant change in the level of H2O2 were recorded only in placentae of LD-IMI group. However, all these parameters recorded significant changes in serum of dams, placentae and liver of fetuses at high-dose. In conclusion, exposure of pregnant rats to IMI, particularly at higher-dose, during the period of organogenesis induced fetal teratogenic effects that may be related to its maternal and fetal oxidative damaging impacts.   


1994 ◽  
Vol 142 (2) ◽  
pp. 193-203 ◽  
Author(s):  
B Senthilkumaran ◽  
K P Joy

Abstract Hypothalamic serotonin (5-HT; content and turnover) and monoamine oxidase (MAO) activity were measured in female catfish, Heteropneustes fossilis, after ovariectomy and supplementation with oestradiol-17β (OE2) in the recrudescent and quiescent phases. These factors were correlated with changes in plasma levels of OE2 and gonadotrophin. In the quiescent phase (December), neither ovariectomy nor OE2 supplementation had any significant effect on 5-HT content and MAO activity. Plasma levels of OE2 and gonadotrophin were undetectable in both control and treated fish, indicating that there was no feedback effect. In the recrudescent phase (prespawning, May), ovariectomy caused biphasic responses of MAO activity and 5-HT content. The enzyme activity decreased significantly after 2, 3, 4 and 5 weeks but increased significantly 6 weeks after ovariectomy. The 5-HT content varied in a biphasic manner with a significant increase at 2, 3 or 4 weeks and a significant decrease in week 6; there being no effect in week 5. 5-HT turnover was inhibited significantly only in week 4 after ovariectomy and did not show a biphasic pattern. In the ovariectomized groups, the OE2 level decreased significantly in a progressive manner with a maximum reduction in week 6. The plasma level of gonadotrophin showed a significant bimodal pattern of increase with the peak in week 4 after ovariectomy, indicating a strong negative feedback effect of OE2. The bimodal pattern of pituitary gonadotrophin release could be correlated with a similar pattern of increase in 5-HT content. OE2 treatment of fish which had been ovariectomized 3 weeks previously had dose-dependent effects on the enzyme; the low dose (0·1 μg/g body weight) was stimulatory and the higher doses (0·5, 1·0 and 5·0 μg/g body weight) were inhibitory. The reverse was true for 5-HT content. Serotonergic turnover increased significantly only in the groups given high doses (1·0 and 5·0 μg/g body weight). The low dose of OE2 (0·1 μg/g body weight) restored the gonadotrophin and OE2 levels to those of the sham-ovariectomized vehicle-treated control group, whereas the high doses (0·5, 1·0 and 5·0 μg/g body weight) decreased the release of gonadotrophin in a dose-dependent manner. Our results suggest that OE2 modulates MAO activity to alter hypothalamic 5-HT in a seasonally dependent manner. The ovariectomy-induced changes in plasma levels of gonadotrophin appear to be mediated, at least partly, by the feedback action of OE2 on 5-HT metabolism. Journal of Endocrinology (1994) 142, 193–203


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ndinawe Johnmark ◽  
Hellen W. Kinyi

Abstract Objective Amaranths leaves are rich in ascorbic acid and polyphenol compounds which have antioxidant activity. The aim of this study was to evaluate their in vivo antioxidant activity. The effect of consumption of Amaranth leaf extract on in vivo antioxidant activity, catalase enzyme activity and H2O2 induced oxidative stress in Drosophila melanogaster flies was assessed. Results Consumption of Amaranth leaf extract was associated with increased survival on exposure to H2o2 in a dose dependent manner in Drosophila melanogaster flies. The study concludes that the ethanolic extract of Amaranth leaves offer protection against hydrogen peroxide-induced oxidative stress.


CNS Spectrums ◽  
2009 ◽  
Vol 14 (10) ◽  
pp. 536-546 ◽  
Author(s):  
Stephen M. Stahl

Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.


Crustaceana ◽  
2016 ◽  
Vol 89 (9) ◽  
pp. 1041-1055 ◽  
Author(s):  
P. Xu ◽  
H. Chen ◽  
Y. Xi ◽  
X. Mao ◽  
L. Wang

Cadmium (Cd) is one of the most toxic environmental pollutants, and is known to have multiple toxic effects on many tissues and organs, including the ovaries. However, the mechanisms underlying Cd toxicity on animal ovaries remain unknown. Here we examined the acute and sub-chronic effects of Cd on the ovaries of the freshwater crab,Sinopotamon henanense(Dai, 1975). Acute effects were studied by treating crabs for 3, 5 and 7 days with two Cd concentrations (7.25 or 14.5 mg/l) and sub-chronic Cd treatment was achieved by treating crabs for 7, 14 and 28 days, respectively, with 0.725 or 1.45 mg/l of Cd. Results showed that Cd levels were significantly increased, in both dose- and time-dependent manners in the sub-chronic groups and in a dose-dependent manner in the acute groups. In the sub-chronic groups, the activities of antioxidant enzymes, SOD, CAT and GPx, initially decreased at day 7 or 14, and increased after 14 and/or 28 days, which was accompanied by an increase in malondialdehyde (MDA) and metallothionein (MT) levels. In the acute groups, there were no statistically significant changes in the activities of the antioxidant enzymes nor in the levels of MDA and MT. To conclude, our results suggest that Cd may do more oxidative damage to cells of crab ovaries at sub-chronic exposure than at acute exposure, which is due to Cd-induced oxidative stress.


2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.


2017 ◽  
Vol 43 (4) ◽  
pp. 1449-1459 ◽  
Author(s):  
Renata A. C. Silva ◽  
Andréa F. Gonçalves ◽  
Priscila P. dos Santos ◽  
Bruna Rafacho ◽  
Renan F. T. Claro ◽  
...  

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.


2018 ◽  
Vol 314 (3) ◽  
pp. F462-F470 ◽  
Author(s):  
Yoshifumi Kurosaki ◽  
Akemi Imoto ◽  
Fumitaka Kawakami ◽  
Masanori Yokoba ◽  
Tsuneo Takenaka ◽  
...  

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.


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