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

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.

2021 ◽  
Author(s):  
EMİN ŞENGÜL ◽  
VOLKAN GELEN ◽  
SEMİN GEDİKLİ ◽  
ELİF ERBAS ◽  
ASLIHAN ATASEVER

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.


2021 ◽  
pp. 096032712110305
Author(s):  
P Alısan Suna ◽  
O Cengız ◽  
A Ceyhan ◽  
E Atay ◽  
T Ertekin ◽  
...  

Introduction: In the study, it was aimed to investigate the possible protective effects of curcumin, a potent antioxidant, against the toxic effect of nonylphenol on bone development. Methods: Thirty pregnant female Wistar albino rats were used. The rats were randomly divided into the following five groups; the control group, corn oil group (150 µl/kg/day), nonylphenol group (50 µl/kg/day), curcumin group (100 mg/kg/day) and curcumin + nonylphenol group (100 mg/kg/day + 50 µl/kg/day). The doses were given by gavage from the 5th day to the 20th day of gestation. The fetuses were removed out on the 20th day of pregnancy by cesarean at the end of the study. After the sacrifice of the animals, double skeletal staining in front extremity (clavicula, scapula, humerus, radius, ulna) and hind extremity (femur, tibia, fibula), additionally histological and immunohistochemical examinations in femur bone were performed. Results: The nonylphenol group offspring have the lowest weights of fetuses and placenta, head-to-hip lengths, biparietal and occipitofrontal length, and also, bone length percentage and percentage of the ossification area in all measurements of the front extremity and hind extremity Interestingly, the groups treated with curcumin showed close to the control group in terms of double skeletal staining, histological, and immunohistochemical examinations. Conclusions: Our findings demonstrated an association between bone development and exposure to nonylphenol. The findings suggest that curcumin treatments may be effective in accelerating bone formation.


2021 ◽  
Author(s):  
Zainab Sabry Othman Ahmed ◽  
Mona K. Galal ◽  
Elsayed A. Drweesh ◽  
Khaled S. Abou-El-Sherbini ◽  
Eman A.M. Elzahany ◽  
...  

Melamine and its analogues are illegally added to raise the apparent protein content in foods. The elevated concentrations of these compounds cause adverse effects in humans and animals. In this contribution, the protective effects of the synthesized starch-stabilized selenium nanoparticles (Se-NPs@starch) on melamine-induced hepato-renal toxicity have been systematically investigated. The Se-NPs@starch were characterized by X-ray photoelectron spectroscopy (XPS) analysis, energy dispersive spectroscopy (EDS) mapping analysis, TEM, and FT-IR. Starch plays a crucial role in the stabilization and dispersion of Se NPs, as noticed from the TEM and EDS investigations. Furthermore, the atomic ratio of Se distribution over the starch surface is approximately 1.67%. The current study was conducted on four groups of adult male rats, and the oral daily treatments for 28 days were as follows: group I served as control, group II received Se-NPs@starch, group III was exposed to melamine, while group IV was treated with melamine and Se-NPs@starch. The results reveal a significant alteration in the histoarchitecture of both hepatic and renal tissues induced by melamine. Furthermore, elevated liver and kidney function markers, high malondialdehyde, and increased expression levels of apoptosis-related genes besides a reduction in GSH and expression levels of antioxidant genes were observed in the melamine-exposed group. Interestingly, the administration of the Se-NPs@starch resulted in remarkable protection of rats against melamine-induced toxicity through increasing the antioxidant capacity and inhibiting oxidative damage. Collectively, this study provides affordable starch-stabilized Se-NPs with potent biological activity, making them auspicious candidates for prospective biomedical applications.


Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
E.M. Vasconcelos ◽  
F.C. Costa ◽  
A.V.N. Azevedo ◽  
P.A.A. Barroso ◽  
E.I.T. de Assis ◽  
...  

Summary This study aimed to investigate the effects of eugenol on growth, viability, antrum formation and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 1 (GPX1) and peroxiredoxin 6 (PRDX6) in bovine secondary follicles cultured in vitro. To this end, bovine ovaries were collected from a local slaughterhouse and in the laboratory the follicles were isolated from the ovarian cortex. The follicles were then cultured in TCM-199+ alone or supplemented with different concentrations of eugenol (0.5, 5.0 and 50.0 μM). Follicular diameters and antrum formation were evaluated on days 0, 6, 12 and 18. Viability analysis was performed using calcein and ethidium homodimer. Real-time PCR was used to quantify mRNA levels for SOD, CAT, GPX1 and PRDX6 in cultured follicles. Follicular diameters and mRNA levels in follicles cultured in vitro were compared using analysis of variance and Kruskal–Wallis tests, while follicular survival and antrum formation were compared using the chi-squared test (P < 0.05). The results showed that secondary follicles cultured with eugenol maintained similar morphology and viability to follicles cultured in the control group. A progressive increase in follicular diameter was observed between days 0 and 12 for all treatments, except for follicles cultured with 50 µM eugenol. Eugenol (5.0 and 50.0 μM) increased mRNA levels for GPX1 in cultured follicles, but 0.5 μM eugenol reduced mRNA levels for SOD. The addition of eugenol did not influence mRNA expression for CAT and PRDX6. In conclusion, eugenol supplementation reduces mRNA levels for SOD and increases mRNA levels of GPX1 in bovine secondary follicles cultured in vitro.


Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.


2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang

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.


CNS Spectrums ◽  
2017 ◽  
Vol 24 (03) ◽  
pp. 333-337 ◽  
Author(s):  
Maiara Zeni-Graiff ◽  
Adiel C. Rios ◽  
Pawan K. Maurya ◽  
Lucas B. Rizzo ◽  
Sumit Sethi ◽  
...  

IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset.ObjectiveThis work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC).MethodsThirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits.ResultsAfter adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p&lt;0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities.ConclusionOur results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.


Author(s):  
Ranjan Kumar Giri ◽  
Sunil Kumar Kanungo ◽  
Saroj Kumar Patro ◽  
Minaketan Sahoo ◽  
Dibya Sundar Panda

Lipid lowering effect of polyherbal formulations using eight different plants was evaluated in triton and diet induced hyperlipidemic models of wistar albino rats. Formulations such as Tablet, Syrup and Suspension inhibited the elevation in serum cholesterol and triglyceride levels on Triton WR 1339 administration rats. The formulations at the same dose level significantly attenuated the elevated serum total cholesterol and triglycerides with an increase in high-density lipoprotein cholesterol in high-fat diet-induced hyperlipidemic rats. The standard drug Niacin showed slightly better effects. The treatment with herbal formulations produced 30-35 percentage improvement in oral glucose tolerance. Similarly all the formulations also reduced the elevated C-reactive protein which is a marker of Hyperlipidemia. In histopathological study it was found that treatment of polyherbal formulation significantly reduced the plaque size in aorta compared with HFD treated control group. The outcome of the study reveals the lipid lowering activity of polyherbal formulations in dyslipidaemic conditions by interfering with the biosynthesis of cholesterol and utilization of lipids.


1998 ◽  
Vol 79 (3) ◽  
pp. 305-309 ◽  
Author(s):  
D. A. Adelekan ◽  
D. I. Thurnham

Riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. The objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (EC1.11.1.9; GPx) and superoxide dismutase (EC1.15.1.1; SOD) in rats infected withPlasmodium bergheimalaria. Riboflavin in its co-enzyme form, FAD, is required by glutathione reductase (EC1.6.4.1) to regenerate GSH and GSH is an important cellular antioxidant both in its own right and also as a substrate for the enzyme GPx. Weanling rats were deprived of riboflavin for 8 weeks before intraperitoneal injection of 1 × 106P. bergheiparasites. Control animals were weight-matched to the respective riboflavin-deficient group. At 10d post-infection, parasite counts were higher in the weight-matched control group than the riboflavin-deficient group (P= 0.004). GPx activity was higher in erythrocytes of rats parasitized withP. bergheithan comparable non-infected rats regardless of riboflavin status (P< 0.05). As mature erythrocytes do not synthesize new protein, the higher GPx activities were probably due to the presence of the parasite protein. In erythrocytes from riboflavin-deficient rats, GPx activity tended to be lower than in those rats fed on diets adequate in riboflavin (weight-matched controls) whether parasitized or not, but the difference was not significant. Neither riboflavin deficiency nor malaria had any effect on erythrocyte SOD activity. It was concluded that riboflavin deficiency has no marked effect on erythrocyte GPx or SOD activity in the rat.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Lyudmil Terziev ◽  
Violeta Dancheva ◽  
Veneta Shopova ◽  
Galya Stavreva

Aim. To investigate the effects of MnTE-2-PyP on some markers of antioxidant defence system in asthma mice model.Material and Methods. The animals were divided into four groups: group 1, controls; group 2, injected with ovalbumin, group 3, treated with MnTE-2-PyP, and group 4, treated with ovalbumin and MnTE-2-PyP. The activities of superoxide dismutase, catalase, glutathione peroxidase and nonprotein sulfhydryl groups content (NPSH) were determined in lung homogenate.Results. The activities of superoxide dismutase and catalase in group 2 decreased significantly as compared to control group. The decrease of the same enzymes in group 4 was lower and significant as compared to group 2. Changes in the glutathione peroxidase activity showed a similar dynamics. The NPSH groups content decreased in group 2. In group 4 this decrease was relatively lower as compared to group 2.Conclusions. The application of MnTE-2-PyP mitigated the effects of oxidative stress in asthma mice model.


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