Hepatoprotective and antineoplastic potencial of red propolis produced by the bees Apis mellifera in the semiarid of Rio Grande do Norte, Brazil

ABSTRACT: The objective of this study was to evaluate the hepatoprotective effect of the honey bee Apis mellifera ethanolic extract of the red propolis, obtained in four municipalities of the Rio Grande do Norte semi-arid region, through an in vitro evaluation of the antineoplastic potential in human hepatic carcinoma (HepG2) and normal cell lines (L929), and from the comet assay in hepatic cell lines (ZF-L hepatocytes) to evaluate the genoprotective potential of the extract. The hepatoprotective effect was also evaluated in vivo by the induction of chronic experimental hepatic lesions in rodents (Rattus norvegicus Berkenhout, 1769), Wistar line, by intraperitoneal administration of thioacetamide (TAA) at the dose of 0.2g/kg. The animals were distributed in the following experimental groups: G1 (control), G2 (treated with 500mg/kg ethanolic extract of propolis), G3 (treated with 500mg/kg of ethanolic extract and TAA) and G4 (treated with TAA). All rats were submitted to serum biochemical, macroscopic, histological and stereological biochemical exams of the liver. It was verified the genoprotective effect of red propolis since the mean damages promoted to DNA in cells tested with the extract were significantly lower than the mean of the positive control damage (hydrogen peroxide). The red propolis extract did not present cytotoxic activity to the tumor cells of human liver cancer, as well as to normal ones. The absence of cytotoxicity in normal cells may indicate safety in the use of the propolis extract. The results of the serum biochemical evaluation showed that the serum levels of the aminotransferase enzymes (AST) did not differ significantly between G1, G2 and G3 when compared to each other. G4 showed significant increase in levels compared to the other groups, indicating that the administration of the extract did not cause liver toxicity, as well as exerted hepatoprotective effect against the hepatic damage induced by TAA. The G3 and G4 animals developed cirrhosis, but in G3 the livers were characterized by the presence of small regenerative nodules and level with the surface of the organ, whereas in G4 the livers showed large regenerative nodules. The livers of the G1 and G2 animals presented normal histological appearance, whereas the livers of the G3 animals showed regenerative nodules surrounded by thin septa of connective tissue, and in G4 the regenerative nodules were surrounded by thick septa fibrous connective tissue. The analysis of the hepatic tissues by means of stereology showed that there was no statistical difference between the percentage of hepatocytes, sinusoids, and collagens in G1 and G2. In G3 the percentage of hepatocytes, sinusoids, and collagen did not differ significantly from the other groups. It was concluded that the ethanolic extract of the red propolis exerted a hepatoprotective effect, because it promoted in vitro reduction of the damage to the DNA of liver cells, antineoplastic activity in human hepatocellular carcinoma cell line (HepG2) and did not exert cytotoxic effect in normal cells or was able to reduce liver enzyme activity and the severity of cirrhosis induced by TAA in vivo.

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Role of transferrin in determining internal iron distribution

Blood ◽

10.1182/blood.v49.6.957.bloodjournal496957 ◽

1977 ◽

Vol 49 (6) ◽

pp. 957-966

Author(s):

P Pootrakul ◽

A Christensen ◽

B Josephson ◽

CA Finch

Keyword(s):

Isotope Ratio ◽

Hepatic Uptake ◽

The Other ◽

Iron Salts ◽

Iron Deficient ◽

Loading And Unloading ◽

The Mean

The behavior in vivo of transferrin in loading and unloading iron from its two sites was examined in rats. Radioiron entering the plasma from the gastrointestinal tract in iron-deficient, normal and iron-loaded rats did not differ in its subsequent tissue distribution between erythroid marrow and liver of normal recipients from a second isotope added to the same plasma in vitro. Loading studies in vitro were then carried out employing a reticulocyte incubation model designed to place one isotope predominantly on one site of transferrin, more available to the erythron, and the second isotope on the other site, more available to the liver. In 15 groups of animals in which 3 different iron salts were employed to load transferrin with iron, the mean isotope ratio in the erythron was 1.03 (+/-0.06 SD) and the mean liver ratio was 0.75 (+/-0.21 SD). It was found that the incubation of plasma with reticulocytes resulted in contamination of the plasma by radioactive hemoglobin. After allowance was made for hepatic uptake of radiohemoglobin in the 13 groups in which proper correction could be made, the isotope ratio in the liver became 0.97 (+/-0.17 SD). It is concluded that iron atoms from the two sites of transferrin have similar tissue distributions in vivo in the experimental situations examined.

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Platelet Involvement After Myocardial Infarction

10.1055/s-0039-1684611 ◽

1979 ◽

Author(s):

J.R. O’Brien ◽

R.I. Handin ◽

M.D. Etherington ◽

R.D. Shuttleworth ◽

W. Calwell

Keyword(s):

Myocardial Infarction ◽

Inverse Correlation ◽

The Other ◽

Interim Report ◽

Clotting Time ◽

Enzymatic Process ◽

Acid Glycoprotein ◽

The Mean

After myocardial Infarction (MI) the Heparin Thrombin Clotting Time (HTCT) of platelet (plt) poor plasma is short, indicating an increase in Heparin Neutralizing Activity (HNA). Plt. Factor 4 (PF4) released in vitro also neutralizes heparin. Does the plasma HTCT in MI reflect PF4 released in vivo? Fifteen patients with MI were compared with 23 controls. The mean HTCT was 43.9 sees, in controls and 14.8 sees, in patients. Plasma PF4 measured by RIA was abnormal in 3 patients but strictly normal in the other 12 (n = 12, mean 3.96 ng/ml; controls n = 22, mean 3.54). There was no correlation between the plasma PF4 and the HTCT. The plts, were frozen and thawed and the patients’ plts, released less HNA (0.17 units/109 plts.) relative to the controls (0.70 units/109plts.) and there was a tight inverse correlation between the plasma HTCT and the intra-plt. HNA. Plts, were isolated and stimulated maximally with thrombin; then malondialdehyde (MDA) production reflecting PG synthesis was monitored fluorometrically. Patients liberated less MDA. (415 ng/109plts.) than the controls (911 ng/plts.). All differences are significant, except the PF4. Plasma fibrinogen and α1 acid glycoprotein were also measured. Thus after an MI and presumably as a result of it, plts, are damaged or “exhausted” as reflected both by a decrease in an enzymatic process - PG synthesis and by a decrease in the content of HNA (? PF4). This interim report also clearly demonstrates that the plasma HTCT does not reflect the same attribute as plasma PF4 detected by RIA.

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Role of transferrin in determining internal iron distribution

Blood ◽

10.1182/blood.v49.6.957.957 ◽

1977 ◽

Vol 49 (6) ◽

pp. 957-966 ◽

Cited By ~ 15

Author(s):

P Pootrakul ◽

A Christensen ◽

B Josephson ◽

CA Finch

Keyword(s):

Isotope Ratio ◽

Hepatic Uptake ◽

The Other ◽

Iron Salts ◽

Iron Deficient ◽

Loading And Unloading ◽

The Mean

Abstract The behavior in vivo of transferrin in loading and unloading iron from its two sites was examined in rats. Radioiron entering the plasma from the gastrointestinal tract in iron-deficient, normal and iron-loaded rats did not differ in its subsequent tissue distribution between erythroid marrow and liver of normal recipients from a second isotope added to the same plasma in vitro. Loading studies in vitro were then carried out employing a reticulocyte incubation model designed to place one isotope predominantly on one site of transferrin, more available to the erythron, and the second isotope on the other site, more available to the liver. In 15 groups of animals in which 3 different iron salts were employed to load transferrin with iron, the mean isotope ratio in the erythron was 1.03 (+/-0.06 SD) and the mean liver ratio was 0.75 (+/-0.21 SD). It was found that the incubation of plasma with reticulocytes resulted in contamination of the plasma by radioactive hemoglobin. After allowance was made for hepatic uptake of radiohemoglobin in the 13 groups in which proper correction could be made, the isotope ratio in the liver became 0.97 (+/-0.17 SD). It is concluded that iron atoms from the two sites of transferrin have similar tissue distributions in vivo in the experimental situations examined.

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Bioactivity Responses of Different Uhmwpe Particles from In-Vivo and In-Vitro Tests

MRS Proceedings ◽

10.1557/proc-662-ll3.8 ◽

2000 ◽

Vol 662 ◽

Author(s):

YoungSoo Park ◽

ShangYou Yang ◽

Paul H. Wooley ◽

Katharine Merritt ◽

Stephen Hsu ◽

...

Keyword(s):

The Other ◽

In Vitro Tests ◽

Textured Surfaces ◽

Aspect Ratios ◽

In Vivo Tests ◽

The Mean ◽

Particle Size And Shape ◽

Ultra High Molecular Weight

AbstractThis paper describes the results of bioactivity responses to different ultra high molecular weight polyethylene (UHMWPE) particles. Particles were produced by a wear tester using two different textures of steel counters, one with cross-hatched and the other with uni-hatched grooves. These two textured surfaces produced two distinct populations of wear particles. One is larger and more elongated (fibril shapes) than the other. The mean sizes and aspect ratios of the particles are in the ranges of 5 μm to 25 μm and about 1.5 to 3, respectively. These two distinct UHMWPE particles were examined through in-vitro and in-vivo tests. Macrophages RAW 264.7 and the murine air-pouch model of inflammation were employed to characterize the effect of the particle size and shape. Preliminary in-vivo tests results showed that more elongated and larger particles enhanced bio-reactions.

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Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647788 ◽

1973 ◽

Vol 29 (02) ◽

pp. 490-498 ◽

Cited By ~ 6

Author(s):

Hiroh Yamazaki ◽

Itsuro Kobayashi ◽

Tadahiro Sano ◽

Takio Shimamoto

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Platelet Rich Plasma ◽

The Other ◽

Endothelial Surface ◽

Important Interaction ◽

Blood Coagulability ◽

The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649648 ◽

1993 ◽

Vol 70 (04) ◽

pp. 676-680 ◽

Cited By ~ 24

Author(s):

H F Kotzé ◽

V van Wyk ◽

P N Badenhorst ◽

A du P Heyns ◽

J P Roodt ◽

...

Keyword(s):

Sialic Acid ◽

Life Span ◽

Blood Platelets ◽

Senescent Cell ◽

Platelet Membrane ◽

Antigen Complex ◽

The Mean ◽

Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

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Cytotoxicity Studies of Curcumin Loaded-Cockle Shell-Derived Calcium Carbonate Nanoparticles

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681209666191128155819 ◽

2019 ◽

Vol 09 ◽

Cited By ~ 1

Author(s):

Maryam Muhammad Mailafiya ◽

Mohamad Aris Mohd Moklas ◽

Kabeer Abubakar ◽

Abubakar Danmaigoro ◽

Samaila Musa Chiroma ◽

...

Keyword(s):

Calcium Carbonate ◽

Safety Margin ◽

Bone Diseases ◽

In Vivo Studies ◽

Normal Cells ◽

Cytotoxicity Studies ◽

Standard Techniques ◽

Cockle Shell

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possess wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attentions. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at higher dose of 500 µg/ml and 40 µg/ml respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone related ailments.

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Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19872317 ◽

1987 ◽

Vol 52 (9) ◽

pp. 2317-2325 ◽

Cited By ~ 5

Author(s):

Jan Hlaváček ◽

Jan Pospíšek ◽

Jiřina Slaninová ◽

Walter Y. Chan ◽

Victor J. Hruby

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

The Other ◽

Amino Acid Residues ◽

Phase Synthesis ◽

Other Hand ◽

Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

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Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

Scientific Reports ◽

10.1038/s41598-020-79940-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Dalal ◽

Abdul Wahab Allaf ◽

Hind El-Zein

Keyword(s):

Theoretical Model ◽

Castor Oil ◽

In Vivo Studies ◽

Coating Materials ◽

Peg 400 ◽

The Mean ◽

Usp Apparatus ◽

Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

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Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽

10.3390/molecules26071838 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1838

Author(s):

Naglaa M. Ahmed ◽

Mahmoud M. Youns ◽

Moustafa K. Soltan ◽

Ahmed M. Said

Keyword(s):

Molecular Modeling ◽

Antitumor Activity ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Antitumor Agents ◽

Cancer Cell Lines ◽

Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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