scholarly journals In vivo liposomal delivery of PPARα/γ dual agonist tesaglitazar in a model of obesity enriches macrophage targeting and limits liver and kidney drug effects

Theranostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 585-601 ◽  
Author(s):  
Victoria Osinski ◽  
Dustin K. Bauknight ◽  
Siva Sai Krishna Dasa ◽  
Matthew J. Harms ◽  
Tobias Kroon ◽  
...  
Keyword(s):  
Drug Effects ◽  
Liver And Kidney ◽  
Liposomal Delivery ◽  
Macrophage Targeting ◽  
Dual Agonist

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.

Preparation and Biochemical Evaluation of Functionalized Multi-Walled Carbon Nanotubes with Punica granatum Extract

2019 ◽  
Vol 15 (1) ◽  
pp. 138-144 ◽  
Author(s):  
Ahmed A. Haroun ◽  
Abdel-Tawab H. Mossa ◽  
Samia M.M. Mohafrash
Keyword(s):  
Liver Enzymes ◽  
Histopathological Analysis ◽  
Pomegranate Peel ◽  
Liver And Kidney ◽  
Multi Walled Carbon Nanotubes ◽  
Pomegranate Peel Extract ◽  
Walled Carbon Nanotubes ◽  
Functionalized Mwcnts ◽  
Peel Extract

Background: Funcionalized multi-walled carbon nanotubes (ox-MWCNTs) were used for the preparation of therapeutic nanoparticles for delivery of some bioactive compounds. Consequently, this work deals with the preparation of grafted MWCNTs with n-vinyl caprolactam in the presence of pomegranate peel extract (P. granatum), titanium dioxide (TiO2) and/or silver nanoparticeles and their toxic effects on male mice using in vivo biological examination (liver and kidney dysfunction biomarkers) and the histopathological analysis. Methods: P. granatum extract was immobilized onto functionalized MWCNTs using simple adsorption technique. Moreover, The prepared materials were analyzed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM). In vivo examination using liver and kidney dysfunction biomarkers was investigated. In addition, the histopathological study was carried out. Results: The ox-MWCNTs induced significant elevation in the liver enzymes including AST, ALT and ALP relative to the control group. While, the treatment with P. granatum extract only did not induce any change in the liver and kidney biomarkers. In other words, P. granatum extract loaded onto functionalized MWCNTs showed low effects on liver enzymes and kidney function biomarkers in the treated mice in comparison with ox-MWCNTs and extract separately. Moreover, histopathological analysis revealed that the P. granatum extract functionalized MWCNTs exhibited normal renal tissue with no histopathological alteration. Conclusion: The grafted MWCNTs with n-vinyl caprolactam in the presence of pomegranate peel extract (P. granatum), titanium dioxide (TiO2) and/or silver nanoparticeles were successfully prepared. SEM-micrographs showed complete coating of MWCNTs fiber with the extract. The prepared materials resulted in no toxic effects and the histopathological findings were confirmed by inflammation of the liver and kidney tissues.

scholarly journals The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett
Keyword(s):  
Insulin Receptor ◽  
Plasma Clearance ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Initial Plasma ◽  
Liver And Kidney ◽  
Pre Treatment ◽  
Initial Clearance

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.

Receptor Specific Macrophage Targeting by Mannose-Conjugated Gelatin Nanoparticles- An In Vitro and In Vivo Study

2010 ◽  
Vol 6 (4) ◽  
pp. 413-421 ◽  
Author(s):  
Shveta Mahajan ◽  
C.K. Prashant ◽  
Veena Koul ◽  
Veena Choudhary ◽  
Amit K. Dinda
Keyword(s):  
In Vivo Study ◽  
Gelatin Nanoparticles ◽  
Macrophage Targeting

scholarly journals Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice

2008 ◽  
Vol 3 ◽  
pp. BMI.S632 ◽  
Author(s):  
Birong Liao ◽  
Eileen McCall ◽  
Karen Cox ◽  
Chung-Wein Lee ◽  
Shuguang Huang ◽  
...  
Keyword(s):  
Whole Blood ◽  
Plasma Cholesterol ◽  
Drug Effects ◽  
Drug Efficacy ◽  
Vascular Wall ◽  
Atherosclerotic Plaques ◽  
Protein Markers ◽  
Novel Approach ◽  
Coa Reductase

Background Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol. Results ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis. Conclusion In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems.

Drug effects on in vivo nasal clearance in rats

1995 ◽  
Vol 116 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Maureen D. Donovan ◽  
Mengping Zhou
Keyword(s):  
Drug Effects ◽  
Nasal Clearance

scholarly journals Opposing Roles of Peroxisome Proliferator-activated Receptor α and Growth Hormone in the Regulation of CYP4A11 Expression in a Transgenic Mouse Model

2009 ◽  
Vol 284 (24) ◽  
pp. 16541-16552 ◽  
Author(s):  
Üzen Savas ◽  
Daniel E. W. Machemer ◽  
Mei-Hui Hsu ◽  
Pryce Gaynor ◽  
Jerome M. Lasker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Transgenic Mice ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Peroxisome Proliferator ◽  
Sexually Dimorphic ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver And Kidney

CYP4A11 transgenic mice (CYP4A11 Tg) were generated to examine in vivo regulation of the human CYP4A11 gene. Expression of CYP4A11 in mice yields liver and kidney P450 4A11 levels similar to those found in the corresponding human tissues and leads to an increased microsomal capacity for ω-hydroxylation of lauric acid. Fasted CYP4A11 Tg mice exhibit 2–3-fold increases in hepatic CYP4A11 mRNA and protein, and this response is absent in peroxisome proliferator-activated receptor α (PPARα) null mice. Dietary administration of either of the PPARα agonists, fenofibrate or clofibric acid, increases hepatic and renal CYP4A11 levels by 2–3-fold, and these responses were also abrogated in PPARα null mice. Basal liver CYP4A11 levels are reduced differentially in PPARα−/− females (>95%) and males (<50%) compared with PPARα−/+ mice. Quantitative and temporal differences in growth hormone secretion are known to alter hepatic lipid metabolism and to underlie sexually dimorphic gene expression, respectively. Continuous infusion of low levels of growth hormone reduced CYP4A11 expression by 50% in PPARα-proficient male and female transgenic mice. A larger decrease was observed for the expression of CYP4A11 in PPARα−/− CYP4A11 Tg male mice to levels similar to that of female PPARα-deficient mice. These results suggest that PPARα contributes to the maintenance of basal CYP4A11 expression and mediates CYP4A11 induction in response to fibrates or fasting. In contrast, increased exposure to growth hormone down-regulates CYP4A11 expression in liver.

Evaluation of Annona muricata (Graviola) leaves activity against experimental trichinellosis: in vitro and in vivo studies

2021 ◽  
Vol 95 ◽  
Author(s):  
E.S. El-Wakil ◽  
H.F. Abdelmaksoud ◽  
T.S. AbouShousha ◽  
M.M.I. Ghallab
Keyword(s):  
Culture Media ◽  
Trichinella Spiralis ◽  
Drug Effects ◽  
In Vivo Studies ◽  
Control Group ◽  
Annona Muricata ◽  
Group I ◽  
Small Intestinal

Abstract Our work aimed to evaluate the possible effect of Annona muricata (Graviola) leaf extract on Trichinella spiralis in in vitro and in vivo studies. Trichinella spiralis worms were isolated from infected mice and transferred to three culture media – group I (with no drugs), group II (contained Graviola) and group III (contained albendazole) – then they were examined using the electron microscope. In the in vivo study, mice were divided into five groups: GI (infected untreated), GII (prophylactically treated with Graviola for seven days before infection), GIII (infected and treated with Graviola), GIV (infected and treated with albendazole) and GV (infected and treated with a combination of Graviola plus albendazole in half doses). Drug effects were assessed by adults and larvae load beside the histopathological small intestinal and muscular changes. A significant reduction of adult and larval counts occurred in treated groups in comparison to the control group. Histopathologically, marked improvement in the small intestinal and muscular changes was observed in treated groups. Also, massive destruction of the cultured adults’ cuticle was detected in both drugs. This study revealed that Graviola leaves have potential activity against trichinellosis, especially in combination with albendazole, and could serve as an adjuvant to anti-trichinellosis drug therapy.

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