scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

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.


2004 ◽  
Vol 61 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Milica Ninkovic ◽  
Zivorad Malicevic ◽  
Vesna Selakovic ◽  
Ivan Simic ◽  
Ivana Vasiljevic

Background. The underlying mechanisms of N-Methyl-3,4-methylenedioxyamphetamine-MDMA-induced hepatotoxicity are still unknown. The aim of this study was to evaluate hepatic oxido-reductive status in the rats liver after the single and repeated administration of MDMA. Methods. MDMA was dissolved in distilled water and administered in the doses of 5 mg, 10 mg, 20 mg, and 40 mg/kg. The animals from the acute experiment were treated per os with the single dose of the appropriate solution, through the orogastric tube. The animals from the chronic experiment were treated per os, with the doses of 5, 10, or 20 mg/kg of MDMA every day during 14 days. The control groups were treated with water only. Eight hours after the last dose, the animals were sacrificed, dissected their livers were rapidly removed, frozen and stored at -70?C until the moment of analysis. The parameters of oxidative stress in the crude mitochondrial fractions of the livers were analyzed. Results. Superoxide dismutase (SOD) activity increased in the livers of the animals that were treated with single doses of MDMA. Chronically treated animals showed the increased SOD activity only after the highest dose (20 mg/kg). The content of reduced glutathione decreased in both groups, but the depletion was much more expressed after the single administration. Lipid peroxidation index increased in dose-dependent manner in both groups, being much higher after the single administration. Conclusion. The increased index of lipid peroxidation and the decreased reduced glutathione levels suggested that MDMA application induced the state of oxidative stress in the liver. These changes were much more expressed after the single administration of MDMA.


2010 ◽  
Vol 22 (9) ◽  
pp. 39
Author(s):  
A. P. Sobinoff ◽  
V. Pye ◽  
B. Nixon ◽  
S. D. Roman ◽  
E. A. McLaughlin

Mammalian females are born with a finite number of non-renewing primordial follicles, the majority of which remain in a quiescent state for many years. These follicles serve as the primary source of all developing oocytes in the ovary, and cannot be regenerated post fetal development. Due to their non-renewing nature, these “resting” oocytes are particularly vulnerable to environmental and toxic insults, especially to those which are capable of inducing oxidative stress. Recent evidence suggests that certain synthetic chemical compounds, known as xenobiotics, have the potential to generate oxidative stress through the production of free oxygen radicals (ROS) as a byproduct of the cell’s detoxification process. Given the redox sensitive nature of the mammalian oocyte, we hypothesise that xenobiotic exposure may have adverse effects on long term oocyte viability. In this study, we attempted to identify the effects of short term xenobiotic exposure on long term oocyte viability. Female Swiss neonatal mice (day 4) were administered 7 daily consecutive doses of 4-Vinylcyclohexene diepoxide (40mg/kg/daily; 80mg/kg/daily) Methoxychlor (50mg/kg/daily; 100mg/kg/daily) or Menadione (7.5mg/kg/daily; 15mg/kg/daily). Mice were then superovulated at 6wks and their oocytes collected for analysis. Sperm-egg fusion assays revealed a significant decrease (P < 0.01) in sperm egg binding (1.4–7 fold) and fusion (4–20 fold) in a dose dependent manner for all three xenobiotic treatments in vivo, signifying a decrease in oocyte membrane fluidity. Follow-up lipid peroxidation analysis on xenobiotic cultured oocytes also showed a significant (P < 0.01) dose dependent increase (1.3–2.5 fold) in membrane lipid peroxidation for each xenobiotic compared to the control. These results provide some of the first evidence of short term xenobiotic exposure causing long term oocyte dysfunction, possibly interfering with the fluidity and/or elasticity of the oocyte plasma membrane through xenobiotic ROS induced lipid peroxidation.


Contrast- induced nephropathy (CIN) is an elevation of serum creatinine of ≥ 0.5 mg/dL from baseline after two to three days of exposure to contrast substance if there is no other cause for acute kidney injury. Atorvastatin may protect normal kidney physiology from contrast- induced kidney injury by effects unrelated to hypolipidemia termed pleiotropic effect by decline of endothelin production, angiotensin system down regulation, and under expression of endothelial adhesion molecules. This study was conducted to assess the strategy by which atorvastatin can achieve protective effect for kidneys after exposure to contrast media in an animal model. A 40 male rats were distributed randomly into 4 groups; ten rats for each: group (1): given normal saline; group (2): CIN group given iopromide as contrast media; group (3): given atorvastatin (20mg/kg) and iopromide; and group (4): given atorvastatin (40mg/kg) and iopromide. Blood collected by cardiac puncture for detection of serum glutathione, malondialdehyde, matrix metalloproteinase-9, and interleukin-18. The results have shown a significant increase in inflammatory and oxidative stress markers in contrast media group, and significant reduction in these markers in atorvastatin treated groups, in a dose-dependent manner. As conclusion, atorvastatin mechanism for protection against CIN in a dose-dependent manner can mediate by anti-inflammatory and antioxidant effects.


Author(s):  
Hadi Shariati ◽  
Mohammad Hassanpour ◽  
Gholamreza Sharifzadeh ◽  
Asghar Zarban ◽  
Saeed Samarghandian ◽  
...  

Objective: The present study has been carried out to evaluate the diuretic and antioxidant properties of pine herb in an animal model. Materials and Methods: 45 adult male rats were randomly divided into nine groups including: groups I (the negative control), groups II (positive control, furosemide 10 mg/kg), groups III to VIII (treatment groups received 100, 200, 400 mg/kg of the aqueous extracts of bark and fruit) and group IX received the combination of aqueous extract of bark (100 mg/kg) and the fruit (100 mg/kg). The urine output, glomerular filtration rate (GFR), electrolytes, urea, and creatinine levels were evaluated . Furthermore, the phenolic content and antioxidant activity of both extracts were also assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and Folin–Ciocalteu methods. Results: The aqueous extracts of the pine bark and fruit increased the urinary output in a dose-dependent manner. The combination of the two extracts compared to the other extracts alone significantly increased the serum potassium level. This study also showed each extract increase creatinine clearance in a dose-dependent manner (p<0.01 and p<0.05). The increase of GFR in the combination group was not significant. The current data showed a significant increase in the total phenolic content in pine bark extract in compared with the fruit extract. Conclusion: The pine bark and fruit can be useful in the prevention and treatment of kidney stones due to the high antioxidant activity.


2021 ◽  
Vol 19 (4) ◽  
Author(s):  
Taslima Nigar ◽  
Annekathryn Goodman ◽  
Shahana Pervin

Abstract Purpose Over the past several decades, research has suggested reactive oxygen species act as cofactors for cervical cancer development. The aim of this study is to evaluate the antioxidant and lipid peroxidation status in cervical cancer patients in Bangladesh. Methods From December 2017 to 2018, a cross-sectional observational study was conducted on 50 cervical cancer patients and 50 controls. Plasma levels of lipid peroxidation and total antioxidant capacity were measured. The Student’s t test was used for statistical analysis. P values less than 0.05 were taken as a level of significance. Results There was a significant reduction in total antioxidant levels in patients with cervical cancer, 972.77 ± 244.22 SD µmol equivalent to ascorbic acid/L, compared to normal controls, 1720.13 ± 150.81 SD µmol equivalent to ascorbic acid/L (P < 0.001). Levels of lipid peroxidation were found to be significantly higher in cervical cancer, 7.49 ± 2.13 SD µmol/L, than in women without cervical cancer, 3.28 ± 0.58 SD µmol/L (P < 0.001). The cervical cancer patients had significantly higher levels of oxidative stress index (0.83 ± 0.31) in comparison to controls (0.19 ± 0.04) (P < 0.001). Conclusion There was an increased oxidative stress index due to imbalance between lipid peroxidation generation and total antioxidant capacity in cervical cancer patients. Further studies are needed to explore the role of oxidative stress as a cofactor for cervical carcinogenesis.


Author(s):  
Nadežda Berzina ◽  
Jurijs Markovs ◽  
Mirdza Apsīte ◽  
Svetlana Vasiļjeva ◽  
Galina Smirnova ◽  
...  

The effects of ascorbic acid supplementation on biomarkers of oxidative stress, cadmium accumulation in organs, immune system activity and kidney function in chickens were investigated. The treatment groups of chickens were fed either plain diet or diet supplemented with ascorbic acid at 100, 500, 1000 and 2000 mg/kg for four weeks. Liver and kidney tissues were assayed for cadmium concentration, and the hepatic levels of ascorbic acid and dehydroascorbic acid (DHAA; the oxidised form), malondialdehyde, glutathione, activity of glutathione peroxidase, blood serum uric acid, creatinine, lysozyme and circulating immune complexes were measured. Supplementation with a high dose of ascorbic acid (1000 and 2000 mg/kg in the diet) caused an imbalance between pro-oxidative and antioxidative activities, and induced a suppressive effect on innate immunity. The results suggest that oxidative stress compromises renal function. We observed that ascorbic acid increased cadmium accumulation in a dose-dependent manner.


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.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Alian Désiré Afagnigni ◽  
Maximilienne Ascension Nyegue ◽  
Chantal Florentine Ndoye Foe ◽  
Youchahou Njankouo Ndam ◽  
Frédéric Nico Njayou ◽  
...  

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days’ subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased (p<0.05) in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease (p<0.05) of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.


Author(s):  
Doraswamy Gangaraju ◽  
Shanmugam Bhasha ◽  
Ravi Sahukari ◽  
Shanmugam Kondeti Ramudu ◽  
Srinivas Kurakula ◽  
...  

A disruption in the equilibrium between the generation of reactive oxygen species and antioxidant defense enzymes is referred to as oxidative stress. In the present study, we planned to identify the hepatoprotective effect of Phyllanthus amarus alkaloid rich fraction in wistar strain albino male rats. The hepatic damage was induced by the D-galactosamine and ameliorative effect was tested with alkaloid rich fraction of P. amarus by measuring oxidative stress markers such as G6PDH, LDH, SDH, MDH and GDH in the liver tissue. Activity levels of G6PDH, SDH, MDH and GDH were significantly decreased in D-galactosamine induced hepatitis rats when compare to normal control rat group, while their activities were significantly increased in hepatitis rat group that supplemented with alkaloid rich fraction of P. amarus. In contrast, LDH enzyme activity of liver was significantly increased in the hepatitis rat group when compare to normal control rats, while its activity was significantly decreased in hepatitis rats treated with alkaloid fraction. In conclusion, it is very clear that alkaloid fraction of P. amarus has hepatoprotective property with respect of decreasing oxidative stress by regulating oxidative stress marker enzymes. The isolation and identification of specific alkaloid compounds with hepatoprotective properties and anti-oxidative stress will require much further research.


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