scholarly journals Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia

2021 ◽  
Vol 22 (7) ◽  
pp. 3473
Author(s):  
Kutilda Soontarapornchai ◽  
Charles L. Cai ◽  
Taimur Ahmad ◽  
Jacob V. Aranda ◽  
Ivan Hand ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intermittent Hypoxia ◽  
Blood Gases ◽  
High Dose ◽  
Golgi Bodies ◽  
Rat Pups ◽  
Layer 2 ◽  
Caffeine Citrate ◽  
High Doses ◽  
Brain Width

(1) Background: Caffeine citrate, at standard doses, is effective for reducing the incidence of apnea of prematurity (AOP) and may confer neuroprotection and decrease neonatal morbidities in extremely low gestational age neonates (ELGANs) requiring oxygen therapy. We tested the hypothesis that high-dose caffeine (HiC) has no adverse effects on the neonatal brain. (2) Methods: Newborn rat pups were randomized to room air (RA), hyperoxia (Hx) or neonatal intermittent hypoxia (IH), from birth (P0) to P14 during which they received intraperitoneal injections of LoC (20 mg/kg on P0; 5 mg/kg/day on P1-P14), HiC (80 mg/kg; 20 mg/kg), or equivalent volume saline. Blood gases, histopathology, myelin and neuronal integrity, and adenosine receptor reactivity were assessed. (3) Results: Caffeine treatment in Hx influenced blood gases more than treatment in neonatal IH. Exposure to neonatal IH resulted in hemorrhage and higher brain width, particularly in layer 2 of the cerebral cortex. Both caffeine doses increased brain width in RA, but layer 2 was increased only with HiC. HiC decreased oxidative stress more effectively than LoC, and both doses reduced apoptosis biomarkers. In RA, both caffeine doses improved myelination, but the effect was abolished in Hx and neonatal IH. Similarly, both doses inhibited adenosine 1A receptor in all oxygen environments, but adenosine 2A receptor was inhibited only in RA and Hx. (4) Conclusions: Caffeine, even at high doses, when administered in normoxia, can confer neuroprotection, evidenced by reductions in oxidative stress, hypermyelination, and increased Golgi bodies. However, varying oxygen environments, such as Hx or neonatal IH, may alter and modify pharmacodynamic actions of caffeine and may even override the benefits caffeine.

scholarly journals Pengaruh Pemberian Curcumin Terhadap Perbaikan Fungsi Hepar Tikus Putih (Rattus Novergicus) yang diinduksi Parasetamol Dosis Tinggi

2021 ◽  
Vol 10 (2) ◽  
pp. 208
Author(s):  
Yolanda Esperanza ◽  
Sulistiana Prabowo ◽  
Fitri Handajani
Keyword(s):  
Oxidative Stress ◽  
Free Radicals ◽  
Cellular Responses ◽  
High Dose ◽  
Toxic Metabolite ◽  
Descriptive Research ◽  
White Rats ◽  
High Doses ◽  
Treat Liver Disease ◽  
Alt Activity

Paracetamol has analgesic properties comparable to NSAIDs, but paracetamol have minimal side effects. Paracetamol is metabolized via sulfation and glucuronidation conjugation which is then excreted in the urine. A small part of the paracetamol has been changed to NAPQI. NAPQI will be detoxified by gluthathione. In high doses, there in an increase in NAPQI and a decrease in glutathione levels that results in oxidative stress and liver cell necrosis. Curcumin is often used as a traditional medicine to treat liver disease where it contains phenolic groups capable to scavenge free radicals. Curcumin extract can improve cellular responses to oxidative stress such as increasing the expression of Nrf2, SOD, and gluthathione. The purpose of this research was to know the effect of curcumin on the improvement of liver function in white rats (Rattus novergicus) induced by high dose  paracetamol. The design of this research was a descriptive research using literature studies from at least 15 international journals indexed by Scimago or national journals indexed by Sinta published in 2015-2020. Based on the journals used in this research, giving curcumin at a dose of 200 mg/kg BW/day for 2 weeks was effective in significantly increasing gluthathione levels in rats receiving high dose paracetamol. Giving curcumin at a dose of 100 mg/kg BW/day for 7 days can reduce AST and ALT activity in rats receiving high dose paracetamol, but the dose of curcumin that was more effective in reducing AST and ALT activity was 200 mg/kg BW/day for 2 weeks. This is because of curcumin which functions as a hepatoprotector that bind directly to the toxic metabolite of paracetamol, thereby reducing the use of glutathione and quench free radicals, so that oxidative stress in the liver decreased and gluthathione levels increased, AST and ALT activity decreased.

scholarly journals Two Faces of Arbutine in Hepatocelluler Carcinoma (HepG2) Cells: Anticarcinogenic Effect in LD50 Dose and Protective Effect Against Cisplatin Toxication Through its Antioxidant and Anti-inflammatory Activity in LD0 Dose  

2021 ◽  
Author(s):  
Ömer Hazman ◽  
Hatice Evin ◽  
Mehmet Fatih Bozkurt ◽  
İbrahim Hakkı Ciğerci
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Low Dose ◽  
Caspase 3 ◽  
High Dose ◽  
Cosmetic Products ◽  
Cytotoxic Effects ◽  
Whitening Agent ◽  
High Doses ◽  
Active Substances

Abstract Arbutine is one of the active substances used as a skin whitening agent in cosmetic products. Possible effects of arbutine on hepatocelluler carcinoma (HepG2) cells and cisplatin toxication in HepG2 cells were investigated in this study. Cytotoxicity, genotoxicity, oxidative stress, inflammation, apoptosis and proliferation levels were determined in experimental groups established for the purpose above. It was determined that when low dose of α-arbutine (in LD0 dose) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low dose of arbutine was used with cisplatin, it was observed that oxidative stress, inflammation, and genotoxicity levels increased as a result of cisplatin toxicity, but caspase 3 levels were not affected by this situation. As a result of high dose (in LD50 dose) of α-arbutine administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In the presented study it was determined that as well as α-arbutine had an anticarcinogenic effect on HepG2 cells in high doses, it might be protective to reduce the side effects caused by low dose (LD0 dose) of cisplatin treatment. In addition, it was concluded that α/β-arbutine-including cosmetic products were safe for cancer patients because α/β-arbutine had no effect on proliferation in HepG2 cells. In order to present the activity of arbutine isoforms more clearly it is recommended that studies should be conducted using healthy and different cell lines.

scholarly journals Two Faces of Arbutine in Hepatocelluler Carcinoma (HepG2) Cells: Anticarcinogenic Effect in LD50 Dose and Protective Effect Against Cisplatin Toxication Through its Antioxidant and Anti-Inflammatory Activity in LD0 Dose

2021 ◽  
Author(s):  
Ömer Hazman ◽  
Hatice Evin ◽  
Mehmet Fatih Bozkurt ◽  
İbrahim Hakkı Ciğerci
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Low Dose ◽  
Caspase 3 ◽  
High Dose ◽  
Cosmetic Products ◽  
Cytotoxic Effects ◽  
Whitening Agent ◽  
High Doses ◽  
Active Substances

Abstract Arbutine is one of the active substances used as a skin whitening agent in cosmetic products. Possible effects of arbutine on hepatocelluler carcinoma (HepG2) cells and cisplatin toxication in HepG2 cells were investigated in this study. Cytotoxicity, genotoxicity, oxidative stress, inflammation, apoptosis and proliferation levels were determined in experimental groups established for the purpose above. It was determined that when low dose of α-arbutine (in LD0 dose) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low dose of arbutine was used with cisplatin, it was observed that oxidative stress, inflammation, and genotoxicity levels increased as a result of cisplatin toxicity, but caspase 3 levels were not affected by this situation. As a result of high dose (in LD50 dose) of α-arbutine administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In the presented study it was determined that as well as α-arbutine had an anticarcinogenic effect on HepG2 cells in high doses, it might be protective to reduce the side effects caused by low dose (LD0 dose) of cisplatin treatment. In addition, it was concluded that α/β-arbutine-including cosmetic products were safe for cancer patients because α/β-arbutine had no effect on proliferation in HepG2 cells. In order to present the activity of arbutine isoforms more clearly it is recommended that studies should be conducted using healthy and different cell lines.

scholarly journals Dose Response of Bumetanide on Aquaporins and Angiogenesis Biomarkers in Human Retinal Endothelial Cells Exposed to Intermittent Hypoxia

2021 ◽  
Vol 14 (10) ◽  
pp. 967
Author(s):  
Sibel Guzel ◽  
Charles L. Cai ◽  
Jacob V. Aranda ◽  
Kay D. Beharry
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Intermittent Hypoxia ◽  
Culture Media ◽  
Tube Formation ◽  
High Dose ◽  
Oxidative Stress Biomarkers ◽  
Vascular Permeability Factor ◽  
Retinal Endothelial Cells ◽  
And Oxidative Stress

Aquaporins (AQPs) are important for regulating cellular water, solute transport, and balance. Recently, AQPs have also been recognized as playing a key role in cell migration and angiogenesis. In the retina, hypoxia induces vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, resulting in retinal edema, which is facilitated by AQPs. Bumetanide is a diuretic agent and AQP 1–4 blocker. We tested the hypothesis that bumetanide suppression of AQPs ameliorates intermittent hypoxia (IH)-induced angiogenesis and oxidative stress in human microvascular retinal endothelial cells (HMRECs). HMRECs were treated with a low-dose (0.05 µg/mL) or high-dose (0.2 µg/mL) of bumetanide and were exposed to normoxia (Nx), hyperoxia (50% O2), or IH (50% O2 with brief hypoxia 5% O2) for 24, 48, and 72 h. Angiogenesis and oxidative stress biomarkers were determined in the culture media, and the cells were assessed for tube formation capacity and AQP-1 and -4 expression. Both doses of bumetanide significantly decreased oxidative stress and angiogenesis biomarkers. This response was reflected by reductions in tube formation capacity and AQP expression. These findings confirm the role of AQPs in retinal angiogenesis. Therapeutic targeting of AQPs with bumetanide may be advantageous for IH-induced aberrant retinal development.

scholarly journals Teratogenic effects of imidacloprid in rats: mechanistic role of oxidative stress

2019 ◽  
Vol 7 (2) ◽  
pp. 35
Author(s):  
Nermeen Borai El-Borai ◽  
Seham Said Hadad ◽  
Hanem Kamal Khalifa
Keyword(s):  
Oxidative Stress ◽  
High Dose ◽  
Dependent Manner ◽  
Teratogenic Effects ◽  
Pregnant Rats ◽  
Skeletal Malformations ◽  
Fetal Malformations ◽  
High Doses ◽  
Dose Dependent

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.   

scholarly journals Investigation of the possible protective effect of Smilax fluminensis steud. leaf in mice subjected to oxidative stress by paracetamol

2021 ◽  
Vol 37 ◽  
pp. e37070
Author(s):  
Ana Paula Simões da Cunha ◽  
Larissa Scremin Ferreira ◽  
Ana Júlia Pasuch Gluzezak ◽  
Edith Eunice Arthur Petrica ◽  
Adilson Paulo Sinhorin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Thiobarbituric Acid ◽  
High Dose ◽  
Glutathione S Transferase ◽  
Leaf Extracts ◽  
Plasma Analysis ◽  
Tropical Regions ◽  
The Face ◽  
High Doses

Paracetamol (PCM) is a drug widely used by the population as an antipyretic and analgesic. If administered in high doses it can cause liver damage, leading to hepatoxicity. The genus Smilax, found in temperate and tropical regions, is traditionally used by the population through the extract of leaves and roots for several conditions, such as in the treatment of syphilis, diabetes, asthma and as a diuretic action. Through this, Smilax fluminensis leaf extracts were used to evaluate the protective effect against oxidative stress induced by a high dose of PCM in mice that received the drug and after receiving treatment with crude extract and fractions. Plasma analysis was performed using as partate aminotransferase (AST), alanine aminotransferase (ALT), glucose, triglycerides and cholesterol, in addition to biochemical techniques such as catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), ascorbic acid (ASA), substances reactive to thiobarbituric acid (TBARS) and carbonylated proteins (CARBONYL) of liver, brain and kidneys. Fraction 1 of the extract was the most promising, decreasing the plasma levels of AST and ALT, the levels of CAT and GST of the liver, together with GSH and in the renal and brain tissue there was a decrease in carbonylated proteins (PCM + F1 versus PCM ). Besides, fraction 1 proved to be hypoglycemic and hypocholesterolemic. It is concluded that fraction 1 of Smilax fluminensis leaves has good antioxidant activity in the face of the damage caused by the high dose of paracetamol.  

The Influence of Serotonin on Clot Retraction and the Thrombelastogram

1958 ◽  
Vol 02 (01/02) ◽  
pp. 111-124 ◽  
Author(s):  
E Deutsch ◽  
K Martiny
Keyword(s):  
Human Plasma ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Specific Effect ◽  
High Dose ◽  
Clot Retraction ◽  
Platelet Counts ◽  
Essential Value ◽  
High Doses ◽  
Free Plasma

Summary1. Normal platelets are necessary for induction of normal clot retraction.2. Serotonin does not induce retraction in human platelet-free plasma-clots or enhance clot firmness as measured in the coagulogram.3. Serotonin does not improve clot retraction or firmness in plasma clots with sub-optimal platelet counts.4. Methylserotonin inhibits clot retraction of platelet-rich plasma to a certain extent in moderate doses, whereas, high doses are ineffective. BOL 148 has a similar, but less significant action. There is a possibility that these effects are specific antiserotonin-effects.5. LSD 25 was ineffective in all concentrations used.6. Largactil and reserpin inhibit retraction in high doses. There seems to be a non specific effect caused by the high dose.7. Reserpine does not release a retraction-inducing agent from the platelets, which could be detected in the centrifuged platelet-free plasma used for the incubation.8. Serotonin does not replace the retraction-cofactor of Hartert, or the dialyzable factor of Lüscher in synthetic clotting substrates.9. Serotonin is of no essential value in inducing normal retraction of human plasma clots.

Influence of β-D-mannuronic acid, as a new member of non-steroidal anti-inflammatory drugs family, on expression pattern of chemokines and their receptors in rheumatoid arthritis

2019 ◽  
Vol 16 ◽  
Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mrna Expression ◽  
Surface Expression ◽  
Phase Iii ◽  
Cell Surface Expression ◽  
Optimum Dose ◽  
High Dose ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
High Doses

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

scholarly journals Comparison of coenzyme Q10 or fish oil for prevention of intermittent hypoxia-induced oxidative injury in neonatal rat lungs

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christina D’Agrosa ◽  
Charles L. Cai ◽  
Faisal Siddiqui ◽  
Karen Deslouches ◽  
Stephen Wadowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lung Injury ◽  
Fish Oil ◽  
Coenzyme Q10 ◽  
Intermittent Hypoxia ◽  
Oxidative Injury ◽  
Adverse Outcomes ◽  
Neonatal Rat ◽  
Antioxidant Systems

Abstract Background Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats. Methods Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (RA) with brief hypoxia (12% O2), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants. Results Of the two neonatal IH paradigms 21%/12% O2 IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities. Conclusions Data suggest that higher FiO2 may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

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