Cyclophosphamide: Interstrain differences in the production of mutagenic metabolites by S9-fractions from liver and kidney in different mutagenicity test systems in vitro and in the teratogenic response in vivo between CBA and C 57 BL mice

1987 ◽  
Vol 7 (4) ◽  
pp. 399-409 ◽  
Author(s):  
K. Winckler ◽  
G. Obe ◽  
S. Madle ◽  
U. Kocher-Becker ◽  
W. Kocher ◽  
...  
Keyword(s):  
Interstrain Differences ◽  
Mutagenicity Test ◽  
Test Systems ◽  
Liver And Kidney

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Experimental Model ◽  
Lethal Dose ◽  
Radical Scavenging ◽  
Cabernet Sauvignon ◽  
Intragastric Administration ◽  
Liver And Kidney ◽  
Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

scholarly journals IN VITRO AND IN VIVO EVALUATION OF 2-CHLOROE THYLN ITROSOUREA DERIVATIVES AS ANTITUMOR AGENTS

2015 ◽  
Vol 37 (1) ◽  
pp. 23-29
Author(s):  
A Sen ◽  
K K Goswami ◽  
A Mallick ◽  
A K Saxena ◽  
U Sanyal ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Agents ◽  
Malignant Tumors ◽  
Optimum Dose ◽  
Mouse Tumor ◽  
Drug Induced ◽  
In Vivo Evaluation ◽  
Liver And Kidney

Aim: To evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphthal-NU, 2-chloroethylnitrosourea compounds with substituted naphthalimide in the pre-clinical studies. Materials and Methods: In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo anti-tumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlich’s carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4+, CD8+ and CD25+ cells in treated mouse were also examined. Results: Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4+ and CD8+ T cells and down regulate CD4+CD25+ regulatory T cells. Conclusion: Overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.

scholarly journals In Vitro Interactions of Artemisinin with Atovaquone, Quinine, and Mefloquine against Plasmodium falciparum

2002 ◽  
Vol 46 (5) ◽  
pp. 1510-1515 ◽  
Author(s):  
S. Gupta ◽  
M. M. Thapar ◽  
W. H. Wernsdorfer ◽  
A. Björkman
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Interaction ◽  
In Vitro Culture ◽  
Effective Concentration ◽  
Interstrain Differences ◽  
Molar Ratios ◽  
The Mean ◽  
In Vitro Interactions

ABSTRACT The interactions of artemisinin with atovaquone, quinine, and mefloquine were investigated in three Plasmodium falciparum strains (strains F-32, FCR-3, and K-1) by an in vitro culture assay. The parasites were cultured for 48 h in the presence of different concentrations and proportions of two drugs at a time in a checkerboard design. The response parameters were determined, and the sums of the fractional inhibitory concentrations (ΣFICs) of the drug combinations were calculated for different degrees of inhibition (50% effective concentration [EC50], EC90, and EC99). Within therapeutically relevant molar ratios (19 to 200), the combination of quinine and artemisinin showed mean ΣFICs of 1.71 at the EC50, 0.36 at the EC90, and 0.13 at the EC99, indicating increasing synergism. Within the range of molar ratios of 4.3 to 50, the combination of mefloquine and artemisinin yielded mean ΣFCIs of 0.93, 0.44, and 0.31 at the EC50, EC90, and EC99, respectively, indicating synergism. The atovaquone combination showed additive activity to synergism at atovaquone/artemisinin proportions considered relevant to the in vivo situation, i.e., between 4.3 and 200, with the mean ΣFICs decreasing from 1.34 at the EC50 to 0.85 and 0.23 at the EC90 and EC99, respectively. Interstrain differences in the degree of drug interaction were seen with the three strains for all combinations. Synergism was most consistent with quinine.

scholarly journals Evaluation of the Anti-angiogenic Activity of Saponins from Maesa lanceolata by Different Assays

2012 ◽  
Vol 7 (9) ◽  
pp. 1934578X1200700
Author(s):  
Kenn Foubert ◽  
Annelies Breynaert ◽  
Mart Theunis ◽  
Rita Van Den Bossche ◽  
Guido R.Y. De Meyer ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Chorioallantoic Membrane ◽  
Rat Aorta ◽  
Cam Assay ◽  
Plant Metabolites ◽  
Angiogenic Activity ◽  
Test Systems ◽  
Aorta Ring

Angiogenesis, in which a vascular network is established from pre-existing vessels, is a complex multistep process. Mechanisms underlying angiogenesis can be investigated using a variety of in vitro, ex vivo and in vivo approaches. Evaluation of several promising plants and plant metabolites, including terpenoids, revealed promising anti-angiogenic activity. Since the maesasaponins displayed anti-angiogenic activity in the chick chorioallantoic membrane (CAM) assay, their activity was further investigated in several test systems. The rat aorta ring assay was compared with the placental vein assay and then selected for the ex vivo investigation of the saponins. Besides their effect on the viability of HUVEC, the anti-angiogenic capacity of the compounds was also investigated in an in vivo zebrafish assay. The activity of the saponins in the viability assay was more pronounced than in the rat aorta ring assay and similar to the effect observed in the CAM assay. The use of different test systems, however, implies different results in the case of saponins.

scholarly journals ACUTE TOXICITY STUDY OF THE LEAVES ETHANOLIC EXTRACT OF PICRIA FEL-TERRAE LOUR.

2018 ◽  
Vol 11 (13) ◽  
pp. 55
Author(s):  
Popi Patilaya ◽  
Dadang Irfan Husori ◽  
Imam Bagus Sumantri ◽  
Simon Sihombing
Keyword(s):  
Acute Toxicity ◽  
Plant Extract ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Ethanolic Extract ◽  
Male Mice ◽  
Plant Leaves ◽  
Liver And Kidney

 Objective: Picria fel-terrae belongs to family Linderniaceae is also known as Pugun tano by Indonesian people. The ethanolic extract of plant leaves has several potential pharmacological activities including antidiabetic, anthelmintic, and antioxidant. However, the toxicity of the plant extract is rarely explored. This work was to investigate toxicity of the leaf ethanolic extract of P. fel-terrae on Artemia salina and male mice.Methods: Acute toxicity of the plant extract was studied by in vitro and in vivo methods. In vitro study was carried out by exposing nauplii to the plant extract at concentrations of 10, 100, 200, 500, and 1000 μg/ml for 48 h. In vivo study was performed on male mice that divided into four groups. Groups I, II, III, and IV were treated with sodium carboxymethyl cellulose 0.5%, the ethanolic extract of plant leaves at doses of 1000, 2000, and 5000 mg/kg bw, respectively. The animal toxic symptoms were observed every day for 14 days. On day 15, the blood of mice was collected to measure alanine aminotransferase, aspartate aminotransferase, and creatinine levels. The effects of plant extract on vital animal organs such as heart, liver, and kidney were also studied. Statistical analysis of data was performed using analysis of variance and followed by Tukey post hoc.Results: The results showed that the leaf ethanolic extract of P. fel-terrae to have weakly toxicity on A. salina with the LC50 of 768.07 μg/ml. At in vivo studies, the toxic symptoms of mice were not identified during experiment with all doses of the plant extract for 14 days. In addition, aspartate aminotransferase and creatinine levels were no significantly different between control and all treatment groups (p>0.05). However, alanine aminotransferase level changed when mice were exposed by the plant extract at the doses of 2.000 and 5.000 mg/kg bw. Although the mice were not dead during experiment, the animal organs such as heart, liver, and kidney were histologically changed.Conclusion: This study suggests that the ethanolic extract of P. fel-terrae leaves has weakly toxicity on A. salina and causes histological changes on male mice organs at the high doses.

Conjugated dopamine: peripheral origin, distribution, and response to acute stress in the dog

1980 ◽  
Vol 58 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Thomas Unger ◽  
Nguyen T. Buu ◽  
Otto Kuchel ◽  
Walter Schürch
Keyword(s):  
Acute Stress ◽  
Surgical Stress ◽  
Direct Conversion ◽  
Peripheral Tissues ◽  
Liver And Kidney ◽  
Arterial Plasma ◽  
Peripheral Origin

Conjugated catecholamines in the circulation and in peripheral tissues were measured together with free catecholamines in an attempt to investigate whether there are in vivo correlates to a possible biological role of dopamine sulfate suggested by an in vitro finding of direct conversion of dopamine sulfate to free norepinephrine by dopamine β-hydroxylase.Following the strong sympathoadrenergic stimulus of surgical stress accompanied by an increase in blood pressure and heart rate, conjugated dopamine showed a twofold rise in arterial plasma (p < 0.005) together with increases of all free catecholamines (0.005 < p < 0.02), while conjugates of noreprinephrine and epinephrine decreased in the circulation (0.01 < p < 0.05). Measurements of arteriovenous differences have shown that release of conjugated dopamine occurred from the adrenal gland during operation along with free catecholamines. However, the venous outflow of conjugated dopamine from liver and kidney did not exceed its arterial influx. Conjugated dopamine, in contrast with other conjugates, is present in adrenals, liver, small intestine, and kidney with higher concentrations than free dopamine in the adrenals (p < 0.01). After ultracentrifugation, the chromaffin granule fraction of the adrenal medulla (site of dopamine β-hydroxylase) contains large amounts of conjugated dopamine (apparently sulfate) suggesting a selective accumulation of dopamine sulfate as a readily available free norepinephrine precursor during stress.These findings establish major in vivo differences between peripheral conjugated dopamine and conjugates of norepinephrine and epinephrine. They suggest that there may be biological roles for conjugated dopamine beyond that of a dopamine metabolite.

scholarly journals Appraisal of Total Phenol, Flavonoid Contents, and Antioxidant Potential of FolkloricLannea coromandelicaUsingIn VitroandIn VivoAssays

Scientifica ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Tekeshwar Kumar ◽  
Vishal Jain
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Properties ◽  
Total Phenolic ◽  
Intragastric Administration ◽  
Total Antioxidant ◽  
Liver And Kidney ◽  
Mda Content ◽  
Phenolic And Flavonoid

The aim of this study was to determine the impending antioxidant properties of different extracts of crude methanolic extract (CME) of leaves ofLannea coromandelica(L. coromandelica) and its two ethyl acetate (EAF) and aqueous (AqF) subfractions by employing various establishedin vitrosystems and estimation of total phenolic and flavonoid content. The results showed that extract and fractions possessed strong antioxidant activityin vitroand among them, EAF had the strongest antioxidant activity. EAF was confirmed for its highest phenolic content, total flavonoid contents, and total antioxidant capacity. The EAF was found to show remarkable scavenging activity on 2,2-diphenylpicrylhydrazyl (DPPH) (EC5063.9 ± 0.64 µg/mL), superoxide radical (EC508.2 ± 0.12 mg/mL), and Fe2+chelating activity (EC506.2 ± 0.09 mg/mL). Based on ourin vitroresults, EAF was investigated forin vivoantioxidant assay. Intragastric administration of the EAF can significantly increase levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels, and decrease malondialdehyde (MDA) content in the liver and kidney of CCl4-intoxicated rats. These new evidences show thatL. coromandelicabared antioxidant activity.

The Primary Investigation on Biological Effect of Mesoporous Bioactive Glass In Vivo

2013 ◽  
Vol 750-752 ◽  
pp. 1651-1655
Author(s):  
Bai Yan Sui ◽  
Cheng Tie Wu ◽  
Jiao Sun
Keyword(s):  
Bioactive Glass ◽  
Biological Effect ◽  
Degradation Products ◽  
Long Term Effect ◽  
Liver And Kidney ◽  
Mesoporous Bioactive Glass

Mesoporous bioactive glass (MBG) has superior bioactivity and degradation than non-mesoporous bioactive glass (BG) in vitro. But the biological effect of MBG in vivo is still unknown. In this study, MBG powders with 20μm were implanted into the femoral condyles in SD rats. BG powders with 20μm were used as a control. The local degradation and osteogenesis were observed at 1 week and 4 weeks after implantation, and the systemic toxicity of the degradation products were also evaluated simultaneously. The results revealed MBG powders had the faster rate of degradation and better osteogenesis effect than BG powders at 4 weeks, although the most of material still remained in situ. Histopathological analyses indicated the degradation products did not have any damage to major organs such as liver and kidney. In conclusion, this preliminary study demonstrated that MBG powders have more excellent biological effect at 4 weeks than that of BG in vivo. However the long-term effect needs to be confirmed.

EFFECT OF LITHIUM ON DEIODINATING ACTIVITY OF VARIOUS RAT TISSUES IN VITRO

1974 ◽  
Vol 76 (2) ◽  
pp. 260-272 ◽  
Author(s):  
P. T. Männistö
Keyword(s):  
Amino Acids ◽  
Lithium Chloride ◽  
Half Life ◽  
Rat Tissues ◽  
Biological Half Life ◽  
Liver And Kidney ◽  
Licl Treatment

ABSTRACT The effect of lithium chloride (LiCl) on the deiodination of iodotyrosines, on the degradation of 125I-L-thyroxine (125I-L-T4) in vitro and on the disappearance of exogenous 125I-L4 and 125I-rat-TSH in vivo was studied in rats. Iodotyrosine deiodination was studied in vitro with three techniques. The whole thyroid lobes were not satisfactory as substrate. When a diluted mixture of prelabelled iodo-amino acids was used as substrate, thyroid homogenates deiodinated iodotyrosines. The reaction was inhibited by boiling and by 3,5-dinitro-L-tyrosine (DNT), but LiCl (2 × 10−2 m) had no effect. When 125I-3-iodo-L-tyrosine (125I-L-MIT) served as substrate, increasing concentrations of thyroid homogenates showed an increasing deicdinating activity, which was stimulated by NADP (1.5 × 10−4 m). Inhibitors of dehalogenase DNT (10−4 and 10 −3 m) and menandione (10−4 m) inhibited deiodination, but LiCl (5×10−3 − 0.1 m) was again without effect. The degradation of 125I-L-T4 by liver and kidney homogenates was inhibited by LiCl (5 × 10−3 − 0.1 m). The disappearance of 125I-L-T4 was studied in rats treated with LiCl for 1 – 4 or 60 – 64 days in vivo. The half-lives were as follows: at 1 –4 days, the control rats 15.9 ± 1.3 h and the LiCl treated rats 19.1 ± 2.1 h (P < 0.05) and at 60 – 64 days 11.2 ± 2.0 h and 66.8 ± 12.3 h (P < respectively. The prolonged half-life in the LiCl treated rats was not due to the decreased excretion of radioactivity in the urine or faeces. The biological half-life of 125I-rat-TSH (11.4 ± 3.2 min) was not modified by LiCl treatment for 5 days. It can be concluded that the antithyroid effect of LiCl neither originates from the inhibition of iodotyrosine deiodination nor from the change in the half-life of TSH. The half-life of thyroxine is prolonged by LiCl, an effect which is perhaps due to the decreased degradation of thyroxine by tissues.

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