Hepatoprotector activity of iridoid glycosides with respect to heliotrine-induced acute toxic liver damage in mice

1999 ◽  
Vol 33 (8) ◽  
pp. 410-412 ◽  
Author(s):  
V. N. Syrov ◽  
A. N. Nabiev ◽  
Z. A. Khushbaktova ◽  
U. V. Zakhidov ◽  
M. S. Maksudov ◽  
...  
Author(s):  
R. A. Hrytsyk ◽  
O. A. Struk ◽  
V. M. Ivanochko

Introduction. Artemisia L. genus species are the promising sources for the manufacturing of drugs with hepatoprotective activity. They are used as appetizing, anthelmintic, bactericidal, choleretic and anti-inflammatory re­medies. The pharmacological activity of Artemisia L. species is caused by the presence of different groups of biologically active substances. The aim of the study – to learn the acute toxicity and the effect of Artemisia absinthium and Artemisia vulgaris water-alcohol extracts on the progress of the toxic tetrachloromethane liver damage. Research Methods. The method of preclinical study of drugs safety was used to determine the acute toxicity. The investigation of hepatoprotective activity of Artemisia absinthium and Artemisia vulgaris extracts was performed using the model of acute tetrachloromethane hepatitis. Hepatoprotector of local manufacturer (“Silibor” tablets) was used as the reference drug. Results and Discussion. It was found that intragastric administration of Artemisia absinthium and Artemisia vulgaris extracts at the dose of 6000 mg/kg does not lead to the death of animals. There were no changes in the integral, hematological, biochemical parameters and in the morphological structure of the internal organs of experimental animals. It allows to characterize the extracts at this dose as almost non-toxic ones (V toxicity class, LD50>5000 mg/kg) according to the toxicity classification of substances. The results of Artemisia absinthium and Artemisia vulgaris extracts study indicate that they show the distinct hepatoprotective activity in condition of acute toxic liver damage. They suppress peroxide destructive processes and reduce the evolution of cytolysis syndrome and their effects are no inferior rather than the effect of tablets “Silibor”. Conclusions. The study of acute toxicity of Artemisia absinthium and Artemisia vulgaris extracts after their intragastric administration at the dose of 6000 mg/kg does not lead to the animals death. They were tidy and had the good appetite. The animals reacted adequately to sound and light stimulation. The processes of urination and defecation were unchanged. Breathing disorders and seizures were not observed. The investigated Artemisia ­absinthium and Artemisia vulgaris extracts demonstrate hepatoprotective activity in condition of acute toxic liver damage. This is proved by decreasing in the intensity of lipid peroxidation and in the toxicity of tetrachloromethane. Biochemical parameters of the animals’ blood and the liver homogenate became responded to the level of intact animals.


2012 ◽  
Vol 92 (5) ◽  
pp. 724-734 ◽  
Author(s):  
Mirko Moreno Zaldivar ◽  
Marie-Luise Berres ◽  
Hacer Sahin ◽  
Andreas Nellen ◽  
Daniel Heinrichs ◽  
...  

Author(s):  
Abbas Abdelhamid Mutawakel ◽  
V. I. Inchina ◽  
T. V. Tarasova ◽  
G. G. Varvanina ◽  
I. E. Trubitsyna

An experimental study of the beneficial effect of herbal preparations on acute toxic liver damage with carbon tetrachloride (CCl4) in animals was conducted The goal is to Compare the hepatoprotective effect of three water extracts of herbal preparations: (I) Trigonella foenum-graecum (seeds), (II) Cymbopogon proximus, (III) Asasia nilotica Material and methods. To simulate acute toxic liver damage, 50% CCl4 was administered once intraperitonally in doses of 0.6 ml, 0.3 ml, and 0.2 ml. Control groups: K1-1 group intact animals without injections; K2: groups 2, 3, 4. introduced saline solution (FR) without Ssl4 in the volume of 2 ml. Experimental groups: 5, 6, 7 and 8 studied the hepatoprotective properties of aqueous solutions of the studied drugs after intraperitoneal administration of Ssl4 or FR. Researched herbs: I, II, III, in different doses were administered 2 ml of an aqueous solution in breeding 1:10, observation period 5 days, the blood, for research stabilized solution of sodium citrate in the ratio of 1:10, studied the properties of blood cells hematological analyzer PCE-90Vet (USA). The content of total protein, albumin, total cholesterol, triglycerides, urea, creatinine and transaminase activity - ALT, AST-were recorded in the blood serum using an automatic analyzer of the company “ HUMASTAR 600 “(Germany)», Results and discussion. Water extracts of preparations I and II prevented the reduction of red blood cells and platelets, and activated the macrophage pool. All the herb extracts studied prevent platelet reduction, however, but do not bring them up to the indicators of intact animals. The use of solution III prevented the growth of the cytolysis enzyme-ALT. All studied extracts in acute carbon tetrachloride intoxication. they warned of an increase in hypertriglyceremia. The introduction of water extracts II, III in the 1:10 ratio prevented the development of necrotic changes in hepatocytes, inflammatory infiltration, manifestations of fatty dystrophy, and preserved the architectonics of the liver lobule.


2020 ◽  
pp. 63-71
Author(s):  
K. O. Kalko ◽  
S. M. Drogovoz ◽  
O. Ya. Mishchenko ◽  
L. B. Ivantsyk ◽  
K. O. Dehtiarova ◽  
...  

Determination of dependence of the efficiency and toxicity of drugs on the time of day or season is one of the most promising areas of modern experimental and clinical pharmacology. The aim of the study. Aim is to identify features of daily rhythms of silymarin influence on the state of antioxidant/prooxidant and cytolytic processes (the leading link in the implementation of hepatoprotective activity) with paracetamol in rats under conditions of acute toxic liver damage. Materials and methods. Chronopharmacological action features of silymarin were studied by use of the generic drug "Karsil" as an example (Sopharma, Bulgaria) with paracetamol in rats under conditions of acute toxic liver damage. The state of the processes of POL-AOS was evaluated by the content of TBA-active products (TBA-AP), the content of recovered glutathione, the activity of SOD, catalase in hepatocytes, and the cytolytic processes by the activity of ALT in serum. Results. There was established a certain chronoarchitectonics of the rhythms of the antioxidant protection system and the activity of the processes of peroxidation in rats under physiological conditions, which was not disturbed by paracetamol on the background of acute liver damage (with the exception of level of acrophase catalase activity). The same dynamics and commonality of rhythms occurred on the background of the use of silymarin. The maximum display of silymarin hepatoprotective activity was observed under conditions of its use in the morning (09.00) and in the evening (21.00). Conclusions. The use of silymarin during periods of maximal display of its hepatoprotective activity, in the morning (09.00) and in the evening (21.00) may be the way to increase its bioavailability. Chronopharmacological features of silymarin activity have been established and should be taken into account when to conduct its further chronopharmacological studies.


2020 ◽  
Vol 17 (3) ◽  
pp. 243-248
Author(s):  
I.Yu. Maklakova ◽  
◽  
V.V. Bazarniy ◽  
D.Yu. Grebnev ◽  
◽  
...  

The aim of this study was to study the effect of combined MMSC and HSC transplantation on liver regeneration under conditions of toxic carbon tetrachloride damage. Materials and methods. The study was performed on white male mice with toxic liver damage by intraperitoneal administration of carbon tetrachloride at a dose of 50 µl per mouse once. An hour after modeling liver damage, placental MMSCs and HSCs were administered intravenously at a dose of 4 million cells/kg and 330 thousand cells/kg, respectively, suspended in 0.2 ml of 0.9% NaCl solution. Control group animals were given 0.9% NaCl solution-0.2 ml intravenously. On days 1, 3, and 7 after cell transplantation, changes in inflammatory activity in the liver were evaluated, and mitotic and apoptotic indices were determined. On the 7th day after the introduction of cells, the activity of DNA repair enzymes of the PARP family was analyzed. Results. Combined MMSC and HSC transplantation leads to a decrease in the index of inflammatory activity in the liver due to a decrease in necrosis, hepatocyte dystrophy, and a decrease in infiltration. As a result of the study, an increase in the activity of PARP repair enzymes was found, which led to a decrease in programmed cell death. Also, cotransplantation of MMSCs and HSCs was accompanied by increased mitotic activity of hepatocytes. Conclusion. Cotransplantation of MMSCs and HSCs under conditions of toxic liver damage reduces the inflammatory response, stimulates the mitotic activity of hepatocytes, and increases the activity of enzymes of the DNA repair system. Activation of the liver's reparative system, in turn, reduces the programmed death of hepatocytes.


2018 ◽  
Vol 82-83 (2-3) ◽  
pp. 51-70 ◽  
Author(s):  
N.M. Bubalo ◽  
G.M. Balan

The objective is to study the incidence of metabolic disorders and effects of obese genes in patients after acute and chronic intoxication with pesticides and to justify methods for evaluating their severity to optimize differentiated therapy and prevention. Material and methods. In 104 agricultural workers after acute poisoning with 2,4-D based herbicides, organophosphorus pesticides and synthetic pyrethroids, and 66 patients with chronic intoxication with pesticides in the initial period and a year later, parameters of oxidative stress, carbohydrate and fat metabolism were studied, depending on the development of toxic liver damage syndrome. In patients after acute poisoning with 2,4-D-based herbicides, imbalance of fatty tissue hormones — leptin, resistin, adiponectin and TNF-α — has also been studied. Conclusion. Dynamic observation has made it possible to establish that in those who have had acute and chronic intoxication with pesticides with toxic liver damage syndrome, metabolic disorders and effects of obese genes develop as the progression of hepatosteatosis develops. The increased level of fatty tissue hormones in the blood — leptin, resistin and TNF-α, at the background of a slight decrease in adiponectin levels in patients who have had poisoning with 2,4-D-based herbicides, allows predicting an increased risk of a progressive course of steatohepatosis and obesity, prevention of which is based on the long-term use of metformin and statins. Key words: metabolic disorders, effects of obese genes, imbalance of fatty tissue, acute and chronic intoxications, pesticides.


2021 ◽  
pp. 116-123
Author(s):  
A. G. Skuratov ◽  
A. N. Lyzikov ◽  
A. S. Shaforost ◽  
A. A. Zyatskov ◽  
N. M. Golubykh

Objective. To evaluate the activity of pyruvate kinase (PK) isoforms in normal conditions, in toxic damage of the liver and during its regeneration.Materials and methods. An experimental study was carried out on 45 Wistar rats. Toxic liver damage was induced by the intraperitoneal administration of carbon tetrachloride. Mechanical damage was simulated by the surgical resection of the liver. The levels of PK isoforms R/L and M in the blood serum and liver tissue of the laboratory animals were measured with an ELISA test.Results. It has been found that the level of PK isoform M signifcantly increases in chronic toxic liver damage, which may indicate the activation of the processes of liver cell proliferation in response to the damaging effect of hepatotoxin (Mann-Whitney U Test: Z = 2.143; p = 0.032). After liver resection, the level of PK R/L, which characterizes the activation of glycolysis, increased and the level of pyruvate kinase M increased signifcantly, which reflected the processes of reparative regeneration in the liver.Conclusion. The serum level of PK isoforms may be used as a laboratory criterion for the activity of reparative regeneration processes, which can be used to evaluate the reparative potential of the liver in case of toxic or mechanical damage, as well as in chronic diffuse diseases.


2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Marie-Luise Berres ◽  
Christian Trautwein ◽  
Mirko Moreno Zaldivar ◽  
Petra Schmitz ◽  
Katrin Pauels ◽  
...  

Abstract The chemokine decoy receptor D6 is a promiscuous chemokine receptor lacking classical signaling functions. It negatively regulates inflammation by targeting CC chemokines to cellular internalization and degradation. Here we analyze the function of D6 in acute CCl4-induced liver damage in constitutive D6-/- and wild-type mice. The degree of liver injury was assessed by liver histology, serum transaminases, IL-6, and TNFα mRNA expression. Protein levels of D6 ligands (CCL2, CCL3, CCL5) and the non-D6-ligand CXCL9 within the livers were determined by ELISAs. The intrahepatic infiltration of immune cells was characterized by FACS. Genetic deletion of D6 led to prolonged liver damage after acute CCl4 administration. The augmented liver damage in D6-/- mice was associated with increased protein levels of intrahepatic inflammatory chemokines CCL2, CCL3, and CCL5 after 48 h, whereas CXCL9 was not different between knockout and wild-type mice. Functionally, increased intra-hepatic CC chemokine concentrations led to increased infiltration of CD45+ leukocytes, which were mainly identified as T and NK cells. In conclusion, the chemokine scavenger receptor D6 has a non-redundant role in acute toxic liver injury in vivo. These results support the importance of post-translational chemokine regulation and describe a new mechanism of immune modulation within the liver.


1986 ◽  
Vol 3 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Martin Døssing

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