Ameliorative Effects of Quercetin in Cyclophosphamide-Induced Vascular Toxicity in Rats

2021 ◽  
Author(s):  
EMİN ŞENGÜL ◽  
VOLKAN GELEN ◽  
SEMİN GEDİKLİ ◽  
ELİF ERBAS ◽  
ASLIHAN ATASEVER
Keyword(s):  
Superoxide Dismutase ◽  
Single Dose ◽  
Corn Oil ◽  
Endothelial Damage ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Vascular Toxicity ◽  
Relaxation Responses

Abstract Cyclophosphamide (CYP) causes vascular toxicity and endothelial damage. In this study aimed the determination of the protective effects of Quercetin (Q) in the CYP-induced vascular toxicity in rats. The rats were randomly divided into the following five groups: Control, CYP, Q50+CYP, Q100+CYP and Q100. The control group was given intragastric (i.g.) corn oil for seven days. The CYP group received i.g. corn oil for seven days and a single dose (200 mg/kg) of CYP via intraperitoneal (i.p.) injection on the seventh day. The rats in the three Q-treated groups received Q for seven days. On the seventh day after the Q treatment, the Q50+CYP, and Q100+CYP groups were injected to single dose (200 mg/kg, i.p.) of CYP. The CYP-treatment both worsen the Phenylephrine (PE)-induced contractions and acetylcholine (ACh)-induced relaxation responses in isolated thoracic aorta of rats, and the application of Q corrected these responses. The malondialdehyde (MDA) levels were significantly higher in the CYP-treated groups. The both dose of Q decreased the MDA level. Superoxide dismutase (SOD) and glutathione (GSH) activities were significantly decreased in the CYP group, whereas the high dose of Q increased SOD and GSH activities. Q treatment attenuated CYP-induced pathologies, and endothelial damage. According to results, Q has protective effects against CYP-induced vascular toxicity in rats.

scholarly journals Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

2010 ◽  
Vol 3 (5) ◽  
pp. 308-316 ◽  
Author(s):  
Yousif A. Asiri
Keyword(s):  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Mrna Expression ◽  
Corn Oil ◽  
Lipid Lowering ◽  
Control Group ◽  
Albino Rats ◽  
Protective Effects ◽  
Antioxidant Genes ◽  
Cardiac Tissues

Cyclophosphamide (CP) is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control) and second (probucol) groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day), respectively, for two weeks. Animals in the third (CP) and fourth (probucol plus CP) groups were injected with the same doses of corn oil and probucol (61 mg/kg/day), respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.). The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) (117%), lactate dehydrogenase (LDH) (64%), free (69%) and esterified cholesterol (42%) and triglyceride (69%) compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP) (40%) and ATP/ADP (44%) in cardiac tissues. Probucol pretreatment not only counteracted significantly the CP-induced increase in cardiac enzymes and apoptosis but also induced a significant increase in mRNA expression of antioxidant enzymes and improved ATP, ATP/ADP, glutathione (GSH) in cardiac tissues. In conclusion, data from the present study suggest that probucol prevents the development of CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to increase mRNA expression of antioxidant genes and to decrease apoptosis in cardiac tissues with the consequent improvement in mitochondrial oxidative phosphorylation and energy production.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Toxicity ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Group Model ◽  
Protective Effects ◽  
Model Group ◽  
Expression Levels

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

scholarly journals The Role and Mechanism of Borneol to Open the Blood-Brain Barrier

2018 ◽  
Vol 17 (3) ◽  
pp. 806-812 ◽  
Author(s):  
Tao Wu ◽  
Aiqin Zhang ◽  
Hongyang Lu ◽  
Qiaoyuan Cheng
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Corn Oil ◽  
Malignant Tumors ◽  
Brain Barrier ◽  
Control Group ◽  
High Dose ◽  
Total Density ◽  
Sd Rats ◽  
Blood Brain

Background: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. Objective: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. Materials and Methods: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy. Results: The concentration of Evans blue in the borneol group was higher than in the control group ( P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group ( P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group ( P < .05). Conclusion: Borneol can open the BBB, which might be related with the increased expression of ICAM-1.

The Effect of Thymol on Renal Toxicity Induced by Mercury Chloride in Rats

2021 ◽  
Author(s):  
Hamid Reza Jamshidi ◽  
Faezeh Taheri
Keyword(s):  
Mercuric Chloride ◽  
Renal Toxicity ◽  
Corn Oil ◽  
Kidney Tissue ◽  
Control Group ◽  
Mercury Chloride ◽  
Protective Effects ◽  
Tissue Samples ◽  
Significant Difference ◽  
Anti Oxidant

Background and Aims: Mercuric chloride is highly toxic once absorbed into the bloodstream, especially the kidneys in which it is collected. Mercury chloride increases hydrogen peroxide and enhances the destruction of protective enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX), leading to oxidative stress. Besides, thymol has anti-oxidant effects and can increase the activity of SOD and GPX. This study aims to evaluate the efficacy of thymol on mercury chloride-induced toxicity. Materials and Methods: In this study, 30 rats, consisting of 6 groups of 5, were used. Control group receiving a single dose of 0.5 mg/kg mercuric chloride for 15 days, third, fourth, and fifth group received intraperitoneal injection of mercuric chloride at a dose of 0.5 mg/kg for 15 days plus thymol at a dose of 10, 30, 50 mg/kg. The sixth group received mercuric chloride at a dose of 0.5 mg/kg for 15 days plus thymol at 30 mg/kg per day for ten days. Results: Results showed a significant difference in the activity of catalase enzyme in kidney tissue samples test. According to the results of SOD, there is a significant difference between the group of corn oil and the group of mercury chloride and between the group of mercury chloride and the group that receives thymol at a dose of 10, 30, 50 mg/kg (p ≤ 0.05). Conclusions: It can be concluded that mercury chloride-induced kidney toxicity and thymol have anti-oxidant protective effects for SOD and GPX.

scholarly journals Protective Effects of Resveratrol against Chronic Immobilization Stress on Testis

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Gulsah Bitgul ◽  
Isil Tekmen ◽  
Didem Keles ◽  
Gulgun Oktay
Keyword(s):  
Immobilization Stress ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Stress Group ◽  
Group I ◽  
Stress Application ◽  
Chronic Immobilization Stress

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n=7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.

New approach for reproductive toxicity assessment: chromatoid bodies as a target for methylmercury and polychlorinated biphenyls in prepubertal male rats

2020 ◽  
Vol 32 (10) ◽  
pp. 914
Author(s):  
M. S. Garcia ◽  
W. A. Orcini ◽  
R. L. Peruquetti ◽  
J. E. Perobelli
Keyword(s):  
Corn Oil ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Reproductive Toxicity ◽  
Treated Group ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
High Dose ◽  
Long Term Effects

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg−1 day−1 MeHg; Aroclor-treated group, which was administered 1mg kg−1 day−1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg−1 day−1) and Aroclor (0.1mg kg−1 day−1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg−1 day−1) and Aroclor (1.0mg kg−1 day−1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg−1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.

scholarly journals Epimedium Polysaccharide Ameliorates Benzene-Induced Aplastic Anemia in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jin He ◽  
Ru Han ◽  
Gongchang Yu ◽  
Martin F. Lavin ◽  
Qiang Jia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Peripheral Blood Cell ◽  
Environmental Pollutant ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Protective Effects

Benzene (BZ) is an important occupational and environmental pollutant. Exposure to BZ may cause aplastic anemia which is characterized as bone marrow hematopoietic failure. In order to reduce the harmful effects of this pollutant, it is necessary to identify additional preventative measures. In this study, we investigated the protective effects of epimedium polysaccharide (EPS), a natural compound with antioxidant and immune-enhancing potency, on aplastic anemia induced by benzene exposure in mice. Male CD-1 mice were randomly divided into five groups including control, BZ (880 mg/kg), LE (EPS low-dose, 20 mg/kg + BZ), ME (EPS middle-dose, 100 mg/kg + BZ), and HE (EPS high-dose, 200 mg/kg + BZ) groups. Animals were exposed to BZ by subcutaneous injection in the presence or absence of EPS via oral administration. All mice were treated 3 times a week for 8 consecutive weeks to develop a mouse model of benzene-induced aplastic anemia (BIAA). Results showed that BZ induced a significant decrease in both white and red blood cells, platelet counts, and hemoglobin level compared with that in the control group (p<0.01). Treatment of EPS led to a protective effect against these changes particularly in the highest-dose group (HE, p<0.01). EPS also recovered the decreased number of nucleated cells in peripheral blood cell smears and femur biopsies by BZ exposure. The increased level of reactive oxygen species (ROS) in bone marrow mononuclear cells (BMMNCs) in mice from the BZ group was significantly lower (p<0.01) in the mice from the highest concentration of EPS (HE) group when compared with that from the control group. In addition, BZ exposure led to a significant increase in the apoptosis rate in BMMNCs which was prevented by EPS in a dose-dependent manner (p<0.01). The antiapoptosis effect of EPS was through reversing apoptotic proteins such as BAX, Caspase-9 and Caspase-3, and Bcl-2. Finally, EPS treatment partially restored the levels of T cells and the different subtypes except CD80+ and CD86+ compared with the BZ group (HE, p<0.05). These results suggest that EPS has protective effects against BIAA via antioxidative stress, immune modulation, and antiapoptosis mechanisms.

Effect of human recombinant superoxide dismutase on canine myocardial infarction

1990 ◽  
Vol 258 (2) ◽  
pp. H369-H380 ◽  
Author(s):  
B. S. Patel ◽  
M. O. Jeroudi ◽  
P. G. O'Neill ◽  
R. Roberts ◽  
R. Bolli
Keyword(s):  
Superoxide Dismutase ◽  
Infarct Size ◽  
Low Dose ◽  
Coronary Occlusion ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Collateral Flow ◽  
Tetrazolium Chloride ◽  
Arterial Blood

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) “low-dose” h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) “high-dose” h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

scholarly journals Modulatory Effect of Fermented Papaya Extracts on Mammary Gland Hyperplasia Induced by Estrogen and Progestin in Female Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhenqiang You ◽  
Junying Sun ◽  
Feng Xie ◽  
Zhiqin Chen ◽  
Sheng Zhang ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Oxidative Dna Damage ◽  
Mammary Glands ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Treatment Groups ◽  
Group A

Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by Aspergillus oryzae and yeasts. In this study, we investigated the protective effects of FPEs on mammary gland hyperplasia induced by estrogen and progestogen. Rats were randomly divided into 6 groups, including a control group, an FPE-alone group, a model group, and three FPE treatment groups (each receiving 30, 15, or 5 ml/kg FPEs). Severe mammary gland hyperplasia was induced upon estradiol benzoate and progestin administration. FPEs could improve the pathological features of the animal model and reduce estrogen levels in the serum. Analysis of oxidant indices revealed that FPEs could increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, decrease malondialdehyde (MDA) level in the mammary glands and serum of the animal models, and decrease the proportion of cells positive for the oxidative DNA damage marker 8-oxo-dG in the mammary glands. Additionally, estradiol benzoate and progestin altered the levels of serum biochemical compounds such as aspartate transaminase (AST), total bilirubin (TBIL), and alanine transaminase (ALT), as well as hepatic oxidant indices such as SOD, GSH-Px, MDA, and 8-oxo-2′-deoxyguanosine (8-oxo-dG). These indices reverted to normal levels upon oral administration of a high dose of FPEs. Taken together, our results indicate that FPEs can protect the mammary glands and other visceral organs from oxidative damage.

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