scholarly journals Zinc Oxide Nanoparticles Alleviate Cyclophosphamide Induced Hepatotoxicity in Male Albino Rats

2020 ◽  
Vol 4 (2) ◽  
Keyword(s):  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Total Bilirubin ◽  
Treated Group ◽  
Nano Particles ◽  
Control Group ◽  
Albino Rats ◽  
Bilirubin Concentration ◽  
Total Bilirubin Concentration ◽  
Day By Day

Background: Cyclophosphamide (CP) is a potent anticancer agent. Its clinical use is restricted because of its marked organ toxicity associated with increased oxidative stress and inflammation. Zinc oxide nanoparticles (nZnO) are one of the most abundantly used nanomaterials in consumer products and biomedical applications. Objectives: The aim of the present study was to evaluate the ameliorative effect of Zn-O nano-particles on hepatotoxicity induced by cyclophosphamide in male albino rats. Materials and Methods: Twenty four adult male rats (Sprague Dawley) were grouped randomly into four groups of six rats each. Group I. Control group: Received 0.2 ml saline /day i.p. injection for 14 days (day by day), group II (CP group): Received CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection, Group III (nZnO group): Received nZnO (5 mg/kg)/day b.w., intraperitoneally for 14 days. Group IV (CP + ZnO NPs group): Received nZnO group: Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, plus CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection. At the end of the experimental period, rats were anesthetized using light ether. Blood and liver samples were taken and prepared for biochemical measurements and histological examination. Results: Serum total proteins, albumin, and globulin levels, were reduced in CP group when compared with the control group. In CP-animals treated with nZnO, these parameters were improved when compared with the CP-treated. A significant elevation in ALT, AST, ALP activities and total bilirubin concentration were observed after CP treatment as compared to vehicle treatment. Co administration of Pretreatment and nZnO with CP were reduced the enzyme activities and total bilirubin concentration significantly, as compared to CP-treated animals. Photomicrograph section of liver of nZnO-treated group showing hepatic lobule and hepatocytes surrounding a central vein and normal sinusoid. Liver of CP treated group reveals lobular infiltrate by chronic inflammatory cells congested hepatic sinusoids containing red blood cells with hepatocytes disarray and cloudy swelling, increased sinusoidal Kupffer cells, and hepatocytes with inculpated or triple nucleated. Photomicrograph of the section of liver of nZnO and CP combination group showed, decrease of the inflammation and infiltration of the portal area. Conclusion: It can be concluded that CP induced hepatotoxicity. Treatment of rats with zinc oxide nano-particles and CP together ameliorated the toxicity induced by CP. These results may provide further visions into proper treatment of patients by improving side effects of chemotherapy. However further studies are necessary to establish optimal doses of nZnO and receive the best safety profile.

scholarly journals Ameliorating Effect of Zinc Oxide Nanoparticles against Hematotoxicity Induced by Cyclophosphamide in Male Albino Rats

2020 ◽  
Vol 3 (1) ◽  
Keyword(s):  
Zinc Oxide ◽  
Body Weight ◽  
Blood Cells ◽  
Intraperitoneal Injection ◽  
Nano Particles ◽  
Male Rats ◽  
Control Group ◽  
Albino Rats ◽  
Group I ◽  
Day By Day

Background: Cyclophosphamide (CP) is a drug with a wide spectrum of clinical uses. Zinc oxide is the most widely used nanoparticles. Nanoparticles could induce oxidative stress that eventually leads to cell toxicity, inflammation and hemolysis. Objectives: The objective of this study was to evaluate the hematological changes induced by Zn-O nano-particles and/or Cyclophosphamide in male rats. Materials and Methods: Twenty four adult male rats (Sprague Dawley) were grouped randomly into four groups of six rats each. Group I. Control group: Received 0.2 ml saline /day i.p. injection for 14 days (day by day), group II (CP group): Received CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection, Group III (nZnO group): Received nZnO (5 mg/kg)/day b.w., intraperitoneally for 14 days. Group IV (CP + ZnO NPs group): Received nZnO group: Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, plus CP 20mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection. At the end of the experimental period, rats were anesthetized using light ether. Blood samples were taken for hematological evaluation. Results: Red blood cells count, hemoglobin concentration, and white blood cells count were significantly decline in rats treated with CP in comparison to control group, while combination of nZnO with CP reduced changes in red bood cells and hemoglobin values. Neutrophils, lymphocytes, eosinophils, and monocytes count were significantly decreased in CP-immunosuppressed group when compared with the control group. In CP-immunosuppressed animals treated with nZnO, these parameters were improved when compared with CP treated groups. Conclusion: It can be concluded that CP induced changes in the hematological parameters. Treatment of rats with zinc oxide nano-particles and CP together ameliorated the toxicity induced by CP. These results may provide further visions into proper treatment of patients by improving side effects of chemotheraby. However further studies are necessary to establish optimal doses of nZnO and receive the best safety profile.

scholarly journals Zinc oxide nanoparticles attenuate the oxidative damage and disturbance in antioxidant defense system induced by cyclophosphamide in male albino rats

2020 ◽  
Vol 4 (1) ◽  
pp. 001-008
Author(s):  
El M Shkal Karema ◽  
Azab Azab Elsayed ◽  
Attia Ahmed M ◽  
El-Banna Sabah G ◽  
Yahya Rabia AM
Keyword(s):  
Zinc Oxide ◽  
Oxidative Damage ◽  
Zinc Oxide Nanoparticles ◽  
Antioxidant Defense ◽  
Antioxidant Defense System ◽  
Nano Particles ◽  
Control Group ◽  
Albino Rats ◽  
Oxide Nanoparticles ◽  
Defense System

Background: Cyclophosphamide is used for the treatment of malignant and non-malignant diseases, but, it induces oxidative damage and disturbance in the antioxidant defense system. Zinc oxide nanoparticles (ZnO NPs) are used in biomedical applications and consumer products. ZnO-NPs are protected cell membranes against oxidative damage, decrease free radicals and malondialdehyde (MDA) levels, and increase the antioxidant enzyme levels. Objectives: The present aimed to evaluate the ameliorative effect of Zn-O nano-particles on oxidative damage and disturbance in the antioxidant defense system induced by cyclophosphamide in male albino rats. Materials and Methods: 24 adult male albino rats were randomly divided into 4 groups (6 rats of each). Group I (Control group): Received 0.2 ml saline /day i.p. injection for 14 days (day by day), group II, (nZnO group): Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, Group III (CP group): Received CP (20 mg/kg/day) b.w, day by day for 14 days by intraperitoneal injection, Group IV (CP + ZnO NPs group): Received nZnO group: Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, plus CP (20 mg/kg/day) b.w., day by day for 14 days by intraperitoneal injection. After 24-hr from the last treatment, all animals were anesthetized using light ether. Blood, lungs, and liver samples were taken and prepared for biochemical measurements. Results: Individual treatment of zinc oxide nanoparticles and CP induced liver cytochrome b5, cytochrome C reductase, and glutathione S-transferase (GST) compared to the control group, while CP increased P450. The combination of nZnO and CP prevents the elevation of cytochrome b5, P450, cytochrome C reductase, and GST compared with the CP treated group. Zinc oxide nanoparticles and CP increased liver thiobarbituric acid reactive substances (TBARS). The combination of nZnO and CP prevents the changes in TBARS concentrations compared with the CP. Injection of CP to rats reduced the activities of serum glutathione reductase (GR) and catalase (CAT) as compared with the control group. However, combination treatment of rats with nZnO and CP increased the activities of these enzymes compared with those treated with CP alone. Zinc oxide nanoparticles and CP increased serum and lung TBARS, while decreased glutathione (GSH) concentration compared to the control group, with more pronounced changes by CP. The combination of nZnO and CP prevents the changes in TBARS and GSH concentrations compared with the CP. Conclusion: It can be concluded that CP induced oxidative stress and disturbance in the antioxidant defense system. Treatment of rats with zinc oxide nano-particles and CP together attenuated the oxidative damage and disturbance in the antioxidant defense system induced by CP. So, Patients treated with CP advised to take nZnO to prevent the side effects of chemotherapy. Further studies are necessary to evaluate the amelioration effect nZnO and other nano-particles against oxidative stress induced by CP in different doses and experimental models.

scholarly journals Single-Dose Pharmacokinetics of Amprenavir, a Human Immunodeficiency Virus Type 1 Protease Inhibitor, in Subjects with Normal or Impaired Hepatic Function

2000 ◽  
Vol 44 (4) ◽  
pp. 821-826 ◽  
Author(s):  
Laurence Veronese ◽  
Jacques Rautaureau ◽  
Brian M. Sadler ◽  
Catherine Gillotin ◽  
Jean-Pierre Petite ◽  
...  
Keyword(s):  
Liver Disease ◽  
Healthy Volunteers ◽  
Total Bilirubin ◽  
Laboratory Data ◽  
Hepatic Insufficiency ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Bilirubin Concentration ◽  
Total Bilirubin Concentration ◽  
Severe Cirrhosis

ABSTRACT Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0–∞) showed an increase in amprenavir AUC0–∞ of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC0–∞ was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC0–∞. The relationship between the total bilirubin concentration and the AUC0–∞ of amprenavir was well characterized by a simple E max model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of α1-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.

scholarly journals Changes in Rats’ Liver Structure Induced by Zinc Oxide Nanoparticles and the Possible Protective Role of Vitamin E

2018 ◽  
Vol 1 (3) ◽  
pp. 1-16 ◽  
Author(s):  
Abdelmonem A. Hegazy ◽  
Marwa M. Ahmed ◽  
Mohammed A. Shehata ◽  
Marwa M Abdelfattah
Keyword(s):  
Zinc Oxide ◽  
Vitamin E ◽  
Zinc Oxide Nanoparticles ◽  
Treated Group ◽  
Protective Role ◽  
Albino Rats ◽  
Oxide Nanoparticles ◽  
Oral Ingestion ◽  
Group 3

Background: Oral ingestion of zinc oxide nanoparticles (ZnONPs) may lead to serious liver injury. Vitamin E (VE) is an important antioxidant factor that can reduce such damage. Aim: This study aimed to evaluate the possible changes that could take place in the liver of adult male albino rats after oral ingestion of ZnONPs and elucidate the potential protective role of VE against such damage. Material and Methods: Forty eight male albino rats were divided into four groups of 12 animals each. Group (1) served as control group and received normal saline. Group (2) “VE-treated” received 100 mg/kg/day of VE dissolved in normal saline by oral gavage for 21 days. Group (3) “ZnONPs-treated” received a daily dose of ZnONPs dispersed in the fresh sterilized physiological saline solution 1mg/kg for 5 constitutive days. Group (4) “concomitant ZnONPs and VE-treated” was pretreated with VE 100 mg/kg/day for 14 days followed by the same dose of ZnONPs as in group (3) for 5 days. The extent of hepatic damage was evaluated by histological and immunohistochemical examination of liver samples and serological analysis of liver enzymes. Results: Body weights and liver weights showed very highly significant decrease (P <0.001) in the ZnONPs-treated group. The histological results in ZnONPs-treated group revealed congested dilated central veins and blood sinusoids, loss of normal arrangement of hepatocytes and most of hepatocytes showed marked vacuolated cytoplasm with darkly stained nuclei. Portal area affection was in the form of congested dilated portal veins with bile duct hyperplasia and cellular infiltration. There was an increase in the mount of blue stained collagen fibers around central veins together with strong positive reaction for Caspase 3 in ZnONPs-treated group. Similarly biochemical analysis indicated that the levels of serum aminotransferase (AST &ALT) significantly increased in ZnONPs-treated group when compared with other groups. Rats pretreated with VE showed improvement of the histological findings and biochemical parameters. Conclusion: Ingestion of ZnONPs could be associated with serious liver affection and pretreatment with VE is suggested to induce some improvement of such deleterious changes.

scholarly journals Functional and Structural Effects of Erythropoietin Subconjunctival Administration in Glaucomatous Animals

2018 ◽  
Vol 3 (2) ◽  
pp. 1-11 ◽  
Author(s):  
Ana Paula Resende ◽  
Serge G. Rosolen ◽  
Telmo Nunes ◽  
Berta São Braz ◽  
Esmeralda Delgado
Keyword(s):  
Neuroprotective Effect ◽  
Treated Group ◽  
Retinal Function ◽  
Function Evaluation ◽  
Control Group ◽  
Albino Rats ◽  
Subconjunctival Injection ◽  
Beneficial Effects ◽  
Structural Evaluation ◽  
Retinal Structure

Purpose: The present study aimed to assess functional and structural benefits of erythropoietin (EPO) when administered subconjunctivally in the retina of glaucomatous rats using electroretinography (ERG) and retinal thickness (RT) measurements. Methods: Glaucoma was experimentally induced in 26 Wistar Hannover albino rats. Animals were divided into 2 groups of 13 animals each: a treated group receiving a unique subconjunctival injection of 1,000 IU of EPO and a control group receiving a saline solution. In each group, 7 animals were used for retinal function evaluation (ERG) and 6 animals were used for retinal structural evaluation (histology). RT was measured, dorsally and ventrally, at 500 μm (RT1) and at 1,500 μm (RT2) from the optic nerve. Results: Retinal function evaluation: for both scotopic and photopic conditions, ERG wave amplitudes increased in the treated group. This increase was statistically significant (p < 0.05) in photopic conditions. Structural evaluation: for both locations RT1 and RT2, the retinas were significantly (p < 0.05) thicker in the treated group. Conclusion: Subconjunctival EPO administration showed beneficial effects both on retinal structure and on retinal function in induced glaucoma in albino rats. This neuroprotective effect should be applied in other animal species.

scholarly journals Enhanced Reduction of Polymicrobial Biofilms on the Orthodontic Brackets and Enamel Surface Remineralization Using Zeolite-Zinc Oxide Nanoparticles-Based Antimicrobial Photodynamic Therapy

2021 ◽  
Author(s):  
Maryam Pourhajibagher ◽  
Abbas Bahador
Keyword(s):  
Zinc Oxide ◽  
Photodynamic Therapy ◽  
Zinc Oxide Nanoparticles ◽  
Enamel Surface ◽  
Orthodontic Brackets ◽  
Control Group ◽  
Oxide Nanoparticles ◽  
Antimicrobial Photodynamic Therapy ◽  
Diagnodent Pen ◽  
Metabolic Activities

Abstract The aim of this study was to evaluate the anti-biofilm and anti-metabolic activities of zeolite-zinc oxide nanoparticles (Zeo\ZnONPs)-based antimicrobial photodynamic therapy (aPDT) against pre-formed polymicrobial biofilms on the orthodontic brackets, as well as, assess the remineralization efficacy on polymicrobial biofilms induced enamel lesions. Following synthesis and characterization of Zeo\ZnONPs, cell cytotoxicity, hemolytic effect, and intracellular reactive oxygen species (ROS) production were determined. The anti-biofilm and anti-metabolic activities of aPDT using different concentrations of Zeo\ZnONPs were investigated. Microhardness tester and DIAGNOdent Pen were used to evaluate the changes of remineralization degree on the treated enamel slabs duration one and three months. No significant cytotoxicity and erythrocyte hemolysis were observed in treated cells with Ze\ZnONPs. When irradiated, suggesting that the Ze\ZnONPs were photoactivated, generating ROS and leading to reduce dose-dependently the cell viability and metabolic activity of polymicrobial biofilms. Also, the enamel surface microhardness value of exposed enamel showed a steady increase with the concentration of Zeo\ZnONPs. No statistically significant differences were shown between aPDT and sodium fluoride varnish as the control group. Overall, Zeo\ZnONPs-based aPDT with the greatest remineralization efficacy of enamel surface can be used as an anti-biofilm therapeutic method, which is involved with their potent ability to produce ROS.

scholarly journals Ameliorating Effect of L-arginine and Insulin on Streptozotocin-induced Adrenal Gland Injury in Albino Rats

1969 ◽  
Vol 11 (3) ◽  
pp. 162-168
Author(s):  
Yasmeen Mahar ◽  
Alisha Qamar ◽  
lnayatullah ◽  
Sarwath Fatimee ◽  
Mohammad Fawad Saeeduddin ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Treated Group ◽  
The Body ◽  
Control Group ◽  
Albino Rats ◽  
Endocrine Gland ◽  
Protective Effects ◽  
Frozen Sections ◽  
Group B

Background:Use of dietary supplements to treat illnesses has increasedtremendously in recentyears.Adrenal gland is one ofthemost commonly damaged endocrine gland in the body, not only by chemical or radiation injuries, but also as a result of differenttypes of stress.Search is underway for use ofnatural foods for protection of adrenal gland from different types ofinsults.Objective: To determine the protective effects of L-arginine on streptozotocin (STZ)-induced adrenal gland injury in albino rats,andto compare its efficacy to insulin.Material and Methods: This prospective experimental study was done at BMSI, JPMC, Karachi. Forty male, healthy albino rats,90-120 days old were segregated into 4 groups. Group A was marked as control, group B was administered STZ, group C and Dwere treated with STZ along with insulin and L-arginine respectively. At the end of study period, i.e., 6 weeks, animals weresacrificed under ether anaesthesia. Tissue from the left adrenal gland was processed for frozen sectioning to observe fat content ofthe adrenal cortex by applying OilRed O stain.Results: Oil Red-0 stained frozen sections revealed closely aggregated fat globules in adrenal cortex of STZ treated group B ascompared to control. Moderate betterment was seen in group C and in group D Oil Red O stained frozen sections as compared toSTZ treated group B.Conclusion: The results ofthe study demonstrated adrenal cortex injury by STZ which ameliorated with concomitant use of insulinandL-arginine. The protection was more pronounced with L-arginine as comparedto insulin.Keywords:STZ, adrenal gland,insulin,L-arginine

scholarly journals Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Shereen Abdelhakim Abdelaleem ◽  
Osama A. Hassan ◽  
Rasha F. Ahmed ◽  
Nagwa M. Zenhom ◽  
Rehab A. Rifaai ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Thioredoxin Reductase ◽  
Serum Cortisol ◽  
Treated Group ◽  
Control Group ◽  
Albino Rats ◽  
Narcotic Drug ◽  
Biochemical Genetic ◽  
Withdrawal Effects

Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this study. The rats were divided into 4 groups (control group, tramadol-treated group, and withdrawal groups). Tramadol was given to albino rats at a dose of 80 mg/kg body weight for 3 months and after withdrawal periods (7–15 days) rats were sacrificed. Long term use of tramadol induced severe histopathological changes in adrenal glands. Tramadol decreased the levels of serum cortisol and DHEAS hormones. In addition, it increased the level of adrenal MDA and decreased the genetic expression of glutathione peroxidase and thioredoxin reductase in adrenal gland tissues. All these changes started to return to normal after withdrawal of tramadol. Thus, it was confirmed that long term use of tramadol can induce severe adrenal insufficiency.

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