scholarly journals Influence of fullerenol C60(OH)24 on enzime status in serum of rats after single dose administration of doxorubicine

2008 ◽  
Vol 62 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Biljana Govedarica ◽  
Vukosava Djordjevic-Milic ◽  
Natasa Radic ◽  
Branislava Srdjenovic ◽  
Aleksandar Djordjevic
Keyword(s):  
Enzyme Activity ◽  
Single Dose ◽  
Free Radicals ◽  
Side Effects ◽  
Topoisomerase Ii ◽  
Control Group ◽  
Limiting Factor ◽  
Dose Administration ◽  
Activity Of Enzymes

The antracycline antibiotics have one of the widest areas of use in oncology. The most investigated mechanisms of their antineoplastic activity include: interactions of these antibiotics with DNA, inhibition of topoisomerase II and production of free radicals. However, the side effects of doxorubicin, especially cardiotoxicity, are the limiting factor of its use in cancer therapy. The aim of this research was to investigate the influence of fullerenol ?60(?H)24 as a cytoprotector in single doze administration of doxorubicin on the activity of enzymes in serum (CK, AST, ALT, LDH and a-HBDH) in rats in in vivo system. Activity of enzymes (CK, LDH, HBDH, AST, and ALT) in serume was measured with standard commercial methods. The results of analysis of the samples treated with the combination of fullerenol and doxorubicin show no difference in enzyme activity in comparison with the control group. The results indicate the possibility of using fullerenol as a protector in the therapy with doxorubicin in malign neoplasm.

scholarly journals A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1606 ◽  
Author(s):  
Enea ◽  
Araújo ◽  
Almeida ◽  
Soares ◽  
Gonçalves-Monteiro ◽  
...  
Keyword(s):  
Single Dose ◽  
Intravenous Administration ◽  
Wistar Rats ◽  
Metabolic Effects ◽  
Control Group ◽  
Gold Nanospheres ◽  
Gold Nanostars ◽  
Different Types ◽  
Metabolomic Approach

Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 × 1011 AuNPs/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects.

scholarly journals Desensitization of Capsaicin-Sensitive Afferents Accelerates Early Tumor Growth via Increased Vascular Leakage in a Murine Model of Triple Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Noémi Bencze ◽  
Csaba Schvarcz ◽  
Gábor Kriszta ◽  
Lea Danics ◽  
Éva Szőke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Enzyme Activity ◽  
Tumor Growth ◽  
Triple Negative ◽  
Vascular Leakage ◽  
Size Difference ◽  
Control Group ◽  
Protease Enzyme

There is growing interest in the role of nerve-driven mechanisms in tumorigenesis and tumor growth. Capsaicin-sensitive afferents have been previously shown to possess antitumoral and immune-regulatory properties, the mechanism of which is currently poorly understood. In this study, we have assessed the role of these terminals in the triple negative 4T1 orthotopic mouse model of breast cancer. The ultrapotent capsaicin-analogue resiniferatoxin (RTX) was used for the selective, systemic desensitization of capsaicin-sensitive afferents. Growth and viability of orthotopically implanted 4T1 tumors were measured by caliper, in vivo MRI, and bioluminescence imaging, while tumor vascularity and protease enzyme activity were assessed using fluorescent in vivo imaging. The levels of the neuropeptides Calcitonin Gene-Related Peptide (CGRP), Substance P (SP), and somatostatin were measured from tumor tissue homogenates using radioimmunoassay, while tumor structure and peritumoral inflammation were evaluated by conventional use of CD31, CD45 and CD3 immunohistology. RTX-pretreated mice demonstrated facilitated tumor growth in the early phase measured using a caliper, which was coupled with increased tumor vascular leakage demonstrated using fluorescent vascular imaging. The tumor size difference dissipated by day seven. The MRI tumor volume was similar, while the intratumoral protease enzyme activity measured by fluorescence imaging was also comparable in RTX-pretreated and non-pretreated animals. Tumor viability or immunohistopathological profile was measured using CD3, CD31, and CD45 stains and did not differ significantly from the non-pretreated control group. Intratumoral somatostatin, CGRP, and SP levels were similar in both groups. Our results underscore the beneficial, antitumoral properties of capsaicin sensitive nerve terminals in this aggressive model of breast cancer, which is presumed to be due to the inhibition of tumor vascular bed disruption. The absence of any difference in intratumoral neuropeptide levels indicates non-neural sources playing a substantial part in their expression.

scholarly journals Influence of age and ways of treatment in the parasitemia in mice infected with Trypanosoma cruzi treated with high potency biotherapy

2021 ◽  
Vol 10 (36) ◽  
pp. 138-141
Author(s):  
Denise Lessa Aleixo ◽  
Paula Fernanda Massini ◽  
Caroline Felicio Braga ◽  
Neide Martins Moreira ◽  
Camila Fernanda Brustolin ◽  
...  
Keyword(s):  
Single Dose ◽  
Trypanosoma Cruzi ◽  
Controlled Trial ◽  
Biological Behavior ◽  
Control Group ◽  
High Potency ◽  
Different Ages ◽  
Microbiological Testing ◽  
Old Mice

Introduction: The infection of mice by Trypanosoma cruzi is well known, making this a good model for understanding the effect of highly diluted medications. Mice of different ages show different responses to biotherapic T. cruzi [1]. Other data from our laboratory using biotherapic treatment at low potencies show that long lasting treatment has a better effect in mice infected with T. cruzi. However, the use of high potency biotherapics in mice of different ages infected with T. cruzi has not been analysed yet. Aim: To evaluate the effect of different ways of treatment using biotherapic 200 DH T. cruzi in the evolution of the curve of parasitemia of mice of different ages infected with T. cruzi. Materials and methods: A blind randomized controlled trial was performed using 107 swiss male mice, aged 28, 35 and 56 days, divided into groups: CONTROL(C) – mice aged 28(C28), 38(C38) and 56(C56) days, treated with 7% water-alcohol solution diluted with water (1mL/100mL); ONE DAY(OD) – mice aged 28(OD28), 38(OD38) and 56(OD56) days, treated with highly diluted medication 200 DH T. cruzi in a single dose, diluted in water (10mL/100mL); EVERY DAY(ED) – mice aged 28(ED28), 38(ED38) and 56(ED56) days, treated with highly diluted medication 200DH T.cruzi until the end of the experiment, diluted in water(1mL/100mL). Amber bottle was used and the water was changed every two days. The groups were infected with strain Y-T. cruzi, intraperitoneal,1400 blood trypomastigotes. Medicines were handled according to the Brazilian Homeopathic Pharmacopoeia [2], with microbiological testing according to RDC n° 67 and in vivo biological risk. We compared the parasitemia curve and total parasitemia, determined daily counting of the parasites [3], obtained using the tests Kruskal-Wallis and Wald-Wolfowitz, Statistica 8.0, 5% significance. Approved by the Ethics Committee for Animal Experimentation/ UEM - 030/2008. Results: The animal age and the ways of treatment used influenced the evolution of the parasitemia curve. This evolution was different among different ages, and the youngest mice of the control group had higher averages of parasitemia ( C28=1.4x106/mL; C38= 1.3 x106/mL and C56=1.0x106/mL ) (fig1). This evolution was not observed in the groups treated daily, in which 56 day-old mice presented a higher parasitemia compared to the other groups ( ED28= 1.3x106/mL; ED38=0.9x106/mL and ED56=1.2x106/mL )(fig1b). For animals treated with a single dose, the energetic stimulus provided by biotherapic caused homogeneity of biological behavior, with significant elevation of parasitemia ( OD28=1.8x106/mL; OD38=1.3x106/mL and OD56=1.5 x106/mL) (fig1c). Likewise, the single dose treatment invariably resulted in an increase of parasitemia when compared to other treatments within the same age group (fig1d-f). The treatment performed daily in animals aged 28 and 38 days showed a decrease in parasitemia (fig1d-f). For 56 day-old mice this fall was not observed (fig1f). The meaning of this finding should be better explored considering the physiological maturity versus the vital energy of mice of different ages. Conclusion: The age and the ways of treatment used are important factors to be considered when using a highly diluted medication. The clinical use of these results in humans, should take into consideration the allometric system of medication dosage which takes into account the metabolic rate of each organism.

scholarly journals Effect of Bifidobacterium Probiotic in the Treatment of Giardiasis Infection in Mice

2019 ◽  
Vol 16 (4) ◽  
pp. 0849
Author(s):  
Israa Mohammad Abd AL-Khaliq
Keyword(s):  
Single Dose ◽  
Giardia Lamblia ◽  
Control Group ◽  
Post Inoculation ◽  
Daily Application ◽  
Probiotic Activity ◽  
Giardia Cysts

Metronidazole therapy is recommended in the treatment of giardiasis,athough some clinical reports mention the resistance to this drug from many pathogens. Many studies were applied to show the effect of probiotic to prevent or to heal diseases of gastrointestine, but only few is known about probiotic activity against infections of protozoa. This study aims to evaluate the efficiency of Bifidobacterium against infection with Giardia lamblia   in experimental mice. It was found that daily application of viable Bifidobacterium cells with a single dose (0.1ml∕mice∕day) significantly reduced the shedding of Giardia lamblia parasite cysts in feces, and infection completely disappeared at the day (15th) post inoculation with this probiotic.  Also, it was noticed that Giardia cysts were reduced in the group treated with metronidazole, and infection cured at day (17th) from treatment, while the control group showed shedding cysts of this parasite. Histopathologically, the effect of Bifidobacterium in vivo by gut cells modulation prevents the colonization of Giardia, leading to reduce the infection with this parasite.

scholarly journals Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

2019 ◽  
Vol 20 (3) ◽  
pp. 530 ◽  
Author(s):  
Po-Kai Huang ◽  
Shian-Ren Lin ◽  
Jirawat Riyaphan ◽  
Yaw-Syan Fu ◽  
Ching-Feng Weng
Keyword(s):  
Single Dose ◽  
Natural Compounds ◽  
Dipeptidyl Peptidase ◽  
Antidiabetic Activity ◽  
Drug Candidate ◽  
Diabetic Patients ◽  
Dose Administration ◽  
Dipeptidyl Peptidase 4

Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

scholarly journals Use of single dose prophylactic antibiotic in routine abdominal hysterectomy - a randomized controlled trial

1970 ◽  
pp. 1-4
Author(s):  
Zaida Rahman
Keyword(s):  
Randomized Controlled Trial ◽  
Single Dose ◽  
Side Effects ◽  
Antimicrobial Therapy ◽  
Controlled Trial ◽  
Prophylactic Antibiotic ◽  
Abdominal Hysterectomy ◽  
Control Group ◽  
Case Group ◽  
Randomized Controlled

A randomized controlled trial was conducted in one unit of Gynecology and Obstetrics Dept. of a Govt. hospital by giving a single dose preoperative prophylactic antibiotic and the results were compared with a control group who received a conventional prophylactic regimen of antibiotic combination. A total of 60 samples were taken from the patients currently admitted and undergoing total abdominal hysterectomy in one unit of the Department of Obstetrics & Gynecology of a Govt. hospital for this trial and they were divided into two groups - 30 Cases and 30 Control. Case group were given a single dose cephradine 1 gm IV just before induction of anesthesia. Control group were given Inj. Ciprofloxacin 200 mg IV 12 hrsly plus inj. Metronidazol 500 mg 8 hrsly till oral feeding followed by oral tab. Ciprofloxacin 500 mg 12 hrsly plus tab. Metronidazol 400 mg 8 hrsly in the remaining days which was then practicing in that gynecology unit of the Govt. hospital. Variables measured for the trial were total cost and duration of antimicrobial therapy, rate of postoperative infection and side effects of antimicrobial therapy. While comparing the outcome between the case and control group, it was observed that both the duration and cost (P<0.001) and also the side effects (P<0.05) of antimicrobial therapy were significantly higher in control group than the case group (duration of antimicrobial therapy was 2.9± 0.88 days in case group and 8. 9±0.58 days in control group and cost of antimicrobial therapy was 113.06± 24.53 taka in case group and 957.376±32.05 taka in control group). But the rate of post operative infection which is the main objective of giving preoperative antibiotic prophylaxis, was significantly higher in case group than the control group (P<0.05). But this infection rate could be reduced if the sterilization procedure of the operation theatre and general conditions of the patients were improved. If these risk factors could be minimized, single dose preoperative prophylactic antibiotic could be effectively practiced in our country. DOI: 10.3329/bjpp.v22i1.3560 Bangladesh J Physiol Pharmacol 2006; 22(1/2) : 1-4

scholarly journals Distribution of selenium in sheep treated with dipheny diselenide

2018 ◽  
Vol 70 (4) ◽  
pp. 1017-1022
Author(s):  
M.L.R. Leal ◽  
J.B.T. Rocha ◽  
C.L.D. Corte ◽  
A.R. Aires ◽  
J.F.X. Rocha ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Dose ◽  
Intravenous Injection ◽  
Selenium Concentration ◽  
Treated Group ◽  
Post Treatment ◽  
Control Group ◽  
Diphenyl Diselenide ◽  
Single Intravenous Injection

ABSTRACT The aim of the present study was to report the in vivo distribution of selenium in sheep. For this, animals were allocated into two groups (control group and treated group) and kept in metabolic cages for a period of 37 days. The treated group received a single dose (6µmol/kg) of Diphenyl Diselenide, intravenously. Plasma and erythrocytes samples were collected at different times. Adipose tissue, muscles (latissimusdorsi, semitendinosus, and supra-scapular) heart, liver, lung, kidney, intestine and brain were sampled at 30 days post-treatment, in order to determine the selenium concentration. The results demonstrated that the selenium, from the Diphenyl Diselenide group, was higher in erythrocytes (4.8mg/L, six hours post-treatment) when compared with the control sheep. The deposition of selenium occurred in the liver (7.01µg/g), brain (3.53µg/g) and kidney (2.02µg/g). After 30 days of a single intravenous injection of Diphenyl Diselenide, liver was the main organ of selenium deposition.

scholarly journals ACETYLCHOLINESTERASE, AS A POTENTIAL BIOMARKER OF NAPHTHALENE TOXICITY IN DIFFERENT TISSUES OF FRESHWATER TELEOST, ANABAS TESTUDINEUS

2021 ◽  
Vol 29 (4) ◽  
pp. 403-409
Author(s):  
Susri Nayak ◽  
Lipika Patnaik
Keyword(s):  
Enzyme Activity ◽  
Control Group ◽  
Anabas Testudineus ◽  
Potential Biomarker ◽  
Maximum Inhibition ◽  
Polycyclic Aromatic ◽  
Acetylcholinesterase Enzyme ◽  
Different Tissues

Naphthalene, a Polycyclic Aromatic Hydrocarbon is widely used as a fumigant and disinfectant despite its toxic effect and is ranked as the ninth most threatening compound. The present study was carried out to determine the in vivo effect of naphthalene at different concentrations on acetylcholinesterase (AChE) enzyme activity in different tissues of Anabas testudineus. The fishes were exposed to varying concentrations of naphthalene (4.2 mgL–1, 4.4 mgL–1, 4.6 mgL–1, 4.8 mgL–1 and 5 mgL–1) for a period of 72 hours. Acetylcholinesterase enzyme activity was found to be significantly inhibited, in a dose-response manner. The inhibition percentage of AChE activity varied from 9.34–43.95% in brain tissue, 2.56–35.81% in liver tissue, 5.94–34.15% in muscle tissue and 3.92–33.75% in gills in comparison to the tissues of the control group. Maximum inhibition of acetylcholinesterase enzyme activity in treated fish was observed in the brain followed by liver, muscles, and gills. This study highlights the significance and role of acetylcholinesterase as a potential stress biomarker of naphthalene toxicity.

scholarly journals The Effect of Single-Dose Ougan Juice Application on the Pharmacokinetics of Erlotinib

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Jin-zhao Yang ◽  
Yi Song ◽  
Jian-hua Xiong ◽  
Yu-xian Lin ◽  
Congcong Wen ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Area Under The Curve ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Control Group ◽  
Intragastric Administration ◽  
Sprague Dawley ◽  
The Difference

The aim of our study was to investigate the effects of single-dose Ougan (Citrus reticulata cv. Suavissima) juice application on the pharmacokinetics of erlotinib in vivo. Twelve Sprague-Dawley rats were randomly divided into the Ougan juice and control groups ( n = 6 each). The rats were given a single dose of 1 mL/100 g Ougan juice or 1 mL/100 g normal saline (NS) by intragastric administration, followed by a single oral administration of 20 mg/kg erlotinib. The plasma concentration of erlotinib in rats was determined using ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Erlotinib-d6 was used as the internal standard for chromatographic analysis on the UPLC BEH C18 analysis column ( 2.1   mm × 50   mm , 1.7 μm). The mobile phase was composed of acetonitrile and 0.1% formic acid eluting by gradient. Different pharmacokinetic (PK) parameters of erlotinib were calculated. The Ougan juice promoted the absorption of erlotinib and reduced the clearance of the drug. The area under the curve of erlotinib in the single-dose Ougan juice pretreatment group was approximately 1.87 times higher, and the maximum blood concentration (Cmax) was approximately 1.34 times higher than that in the control group. The mean residence time of erlotinib in the Ougan juice group was larger, and the clearance rate was smaller than those in the control group; the difference was statistically significant ( P < 0.05 ). Ougan juice affected the PK spectrum of erlotinib in rats by improving the bioavailability of the drug and significantly increasing its plasma concentration.

scholarly journals Zingerone Attenuates Methotrexate-Induced Hepatotoxicity in Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehdi Goudarzi ◽  
Zahra Basir ◽  
Alireza Malayeri ◽  
Ali Nesari ◽  
Narjes Zaeemzadeh
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Hepatic Injury ◽  
Redox System ◽  
Hepatic Tissue ◽  
Control Group ◽  
Histological Changes ◽  
Once Daily ◽  
Tnf Α ◽  
Inflammatory Bowel

Background: Methotrexate (MTX) is mainly used for the chemotherapy of different types of malignancy and some autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease. The MTX application is limited by its severe side effects, including several types of hepatic injury. Objectives: In this study, we decided to evaluate if zingerone (the main constituent of ginger) can reduce the hepatic side effects of MTX. Methods: Thirty-five rats were divided into five groups: Control group receiving normal saline (N/S), once daily, by gavage, for 10 days, and N/S intraperitoneally (i.p.), a single dose on the ninth day; Methotrexate (MTX) group receiving N/S, once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day; Groups 3 (ZG25), 4 (ZG50), and 5 (ZG100) receiving zingerone (25, 50, and 100 mg/kg, respectively), once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day. Results: The results showed a significant decrease in serum AST, ALT, and ALP, as well as the hepatic content of MDA, NO, PC, TNF-α, and IL-1β, in the ZG groups compared with the MTX group. The activity of SOD, CAT, and GPX, as well as the hepatic content of GSH, showed a significant increase in the ZG groups compared with the MTX group. Histopathological improvement in the hepatic tissue of ZG groups compared with the MTX group confirmed all other findings. Conclusions: It is concluded that zingerone can improve hepatic injury induced by MTX in rats regarding the redox system features, inflammation, and histological changes. This can make humans hopeful for using Ginger in the future for attenuating the hepatic side effects of MTX when used chronically.

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