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Title
Inhibition of Kupffer cell functions as an explanation for the
hepatoprotective properties of silibinin.
Author
Dehmlow C; Erhard J; de Groot H
Address
Institut für Physiologische Chemie, Universitätsklinikum,
Essen, Germany.
Source
Hepatology, 23(4):749-54 1996 Apr
Abstract
The flavonoid silibinin, the main compound extracted from the
milk thistle Silybum marianum, displays hepatoprotective properties
in acute and chronic liver injury. To further elucidate the mechanisms
by which it acts, we studied the effects of silibinin on different
functions of isolated rat Kupffer cells, namely the formation
of superoxide anion radical (02-), nitric oxide (NO), tumor necrosis
factor alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), and leukotriene
B(4) (LTB(4)). Production of 02- and NO were inhibited in a dose-dependent
manner, with an 50 percent inhibitory concentration (IC(50))
value around 80 micro mol/L. No effect on TNF-alpha formation
was detected. Opposite effects were found on the cyclooxygenase
and 5-lipoxygenase pathway of arachidonic acid metabolism. Whereas
no influence on PGE(2) formation was observed with silibinin
concentrations up to 100 micro mol/L, a strong inhibitory effect
on LTB(4) formation became evident. The IC(50)-value for inhibiting
the formation of this eicosanoid was determined to be 15 micro
mol/L silibinin. The strong inhibition of LTB(4), formation by
silibinin was confirmed in experiments with phagocytic cells
isolated from human liver. Hence, while rather high concentrations
of silibinin are necessary to diminish free radical formation
by activated Kupffer cells, significant inhibition of the 5-lipoxygenase
pathway already occurs at silibinin concentrations which are
achieved in vivo. Selective inhibition of leukotriene formation
by Kupffer cells can at least partly account for the hepatoprotective
properties of silibinin.
Title
Comparative effects of colchicine and Silymarin on CCl4-chronic
liver damage in rats.
Author
Favari L; Pérez-Alvarez V
Address
Departamento de Farmacología y Toxicologia, Centro de
Investigación y de Estudios Avanzados del IPN, México,
D.F.
Source
Arch Med Res, 28(1):11-7 1997 Spring
Abstract
The comparative effects of colchicine (10 micrograms day-1, p.o.)
and Silymarin (50 mg kg-1, p.o.) each given for 5 days a week
on the chronic carbon tetrachloride (CCl4) liver damage were
studied. Treatment with CCl4 resulted in a marked reduction of
Na+, K+, and Ca2(+)-ATPases in plasma liver membranes as compared
to vehicles or either Silymarin or colchicine alone. Collagen
content in livers of animals treated with CCl4 was increased
about four-fold as compared to controls and histological examination
of liver samples showed that collagen increase distorted the
normal liver architecture. Colchicine or Silymarin treatment
completely prevented all the changes observed in CCl4-cirrhotic
rats (namely, lipid peroxidation, Na+, K+ and Ca(2+)-ATPases),
except for liver collagen content which was reduced only 55%
as compared with CCl4-treated rats and for alkaline phosphatase
and glutamic pyruvic transaminase which still remained above
controls. In the CCl4 + Silymarin group, the loss of glycogen
content was completely prevented. However, when rats were treated
with CCl4 + colchicine, liver glycogen content could not be restored.
The hepatoprotective effects of colchicine or Silymarin were
very similar in regard to the prevention of chronic liver damage.
Title
The effect of Silymarin, a hepatoprotective substance, on liver
histones in irradiated rats
Author
KoÍzurkovÍa M; HakovÍa H; MiÍsÍurovÍa
E
Address
PrÍirodovedeckÍa fakulta UPJS, KoÍsice.
Source
Vet Med (Praha), 39(2-3):85-92 1994
Abstract
Changes of concentration, total content of histones and relative
portions of histone fractions were investigated in the liver
of rats after administration of the hepatoprotective substance
Silymarin (70 mg/kg) and after gamma-irradiation of the whole
body at a dose of 3 Gy, which were examined in 30 hours and in
7 days. Administration of Silymarin alone considerably increased
the concentration, particularly total content of extractable
histones in the liver of rats examined in hour 30. They decreased
below the level of control values after 7 days. The whole body
irradiation at a dose 3 Gy of gamma-radiation caused a steep
fall of the concentration and total content of histones in hour
30, which persisted also on day 7. Silymarin administered 1 hour
before irradiation prevented quantitative changes of histones
in hour 30, after irradiation the fall was still steeper than
after irradiation without Silymarin administration. As Tab. I
shows, a significant decrease in the relative portion of histone
fractions H2A+H2B was found in the extracted histone of the experimental
animals of all 3 groups in hour 30, as well as a decrease in
the fraction H1 after irradiation without Silymarin administration.
A decrease in the lysin-rich-histone portion was related to an
increase in the relative portion of histone H3. In the rats which
were administered Silymarin 1 hour before irradiation these changes
were found to persist until day 7, and they were related to an
increase in the subfraction H1 degree within the histone fraction
H1 (Tab II). Hence the results document that Silymarin administration
1 hour before irradiation had a positive effect which was observed
in all the investigated parameters in hour 30 after irradiation.
But the radioprotective effect of Silymarin was only temporary
while until day 7 after irradiation histone variations were identical
or still larger than after irradiation without Silymarin administration.
Title
Therapeutical effect of Silymarin on nucleic acids in the various
organs of rats after radiation injury.
Author
Haková H; Misúrová E
Address
Department of Cellular and Molecular Biology, P.J. Safarik University,
Kosice, Slovakia.
Source
Radiats Biol Radioecol, 36(3):365-70 1996 May-Jun
Abstract
The therapeutical effect of the hepatoprotective drug Silymarin
(Flavobion) was investigated in rats after total body gamma irradiation
with a dose of 6 Gy. Silymarin (70 mg kg-1 p.o. by tube) was
administered twice a day over 7 and 14 days after irradiation.
At the end of therapy, the effect of Silymarin was evaluated
on the basis of quantitative changes of nucleic acids in the
liver (regenerating after partial hepatectomy), spleen and bone
marrow. It was found that the nucleic acid changes in irradiated
rats were alleviated by the post-radiation application of Silymarin
in its target organ--the liver, but also in the spleen and bone
marrow. We assume that the therapeutical effect of Silymarin
on radiation induced changes of nucleic acids in various tissues
of rats is caused mainly by the activation of cellular metabolism
including the metabolism of nucleic
acids.
Title
Acetaminophen-induced toxicity to human epidermoid cell line
A431 and hepatoblastoma cell line Hep G2, in vitro, is diminished
by Silymarin.
Author
Shear NH; Malkiewicz IM; Klein D; Koren G; Randor S; Neuman MG
Address
Division of Dermatology, Sunnybrook Health Science Centre, Ont.,
Canada.
Source
Skin Pharmacol, 8(6):279-91 1995
Abstract
The skin and liver may be targets for cytotoxicity induced by
oxidative drug metabolites. We used human epidermoid A431 cells
and human hepatoblastoma Hep G2 cells as the experimental model.
The aim of the study was to investigate and evaluate the effect
of Silymarin on acetaminophen (APAP)-induced toxicity under controlled
conditions. Silymarin is known to be a potent antioxidant that
diminishes toxicity induced by a variety of other hepatotoxins
(e.g. Amanita phaloides, algae's toxins, carbon tetrachloride).
Glutathione (GSH) depletion was enhanced by adding to the medium
buthionine sulfoximine [L-buthionine-(S,R)-sulfoximine, BSO].
Cells were incubated with high-concentration 5-20 mM APAP or
alpha-(minimum essential medium for 2-24 h to evaluate the drug's
ability to reduce cytoviability. Viability was then quantitated
by metabolism of the tetrazolium dyes (MTT) and neutral red (NR).
Cytoviability was 100% for controls. For Hep G2 treated for 24
h with 20 mM, APAP viability was 56.0% by MTT and 62.5% by NR.
BSO-treated cells showed an enhanced cytotoxicity, determined
by both assays. Administration of 0.5 mM Silymarin reduced cytotoxicity
significantly. In A431 cells, treatment with 20 mM APAP reduced
viability by 57% (MTT) and 69% (NR) versus control (100%). BSO
further decreased viability. Since incubation with Silymarin
showed significant protection against APAP toxicity, it can be
considered a cytoprotective agent in this in vitro model of drug
toxicity. GSH concentrations in both cell lines decrease significantly
after exposure to 20 mM APAP, or 0.5 mM versus control (p <
0.05), and increased (p < 0.001) if incubated with APAP and
Silymarin. The protective effect could be through mitochondrial
membrane stabilization and/or an increase in available GSH.
Title
The pathology of liver injury induced by the chronic administration
of alcohol and 'low-dose' carbon tetrachloride in Porton rats.
Author
Hall PM; Plummer JL; Ilsley AH; Ahern MJ; Cmielewski PL; Williams
RA
Address
Department of Histopathology, Flinders Medical Centre, Bedford
Park, Australia.
Source
J Gastroenterol Hepatol, 9(3):250-6 1994 May-Jun
Abstract
We have previously established a model for micronodular cirrhosis
by feeding Wistar rats alcohol, in the Lieber-DeCarli liquid
diet, and exposing them to 'low-dose' carbon tetrachloride (CCl4)
vapour for 10 weeks. This study reports the spectrum of liver
pathology seen in male Porton rats exposed to 'low-dose' CCl4
vapour 5 nights/week, 6 h/night while being fed alcohol (300
kcal/L) in the Lieber-DeCarli diet. Micronodular cirrhosis developed
in all animals after 5-7 weeks of treatment. The simultaneous
administration of Silymarin, a putative hepatoprotective agent,
in the liquid diet, did not alleviate or prevent the chronic
liver injury. The histopathological features of the liver injury
are described, with particular emphasis on the presence of small
epithelial cells ('progenitor or stem cell'), which appear to
be playing a role in liver regeneration.
Title
Putative effect of Silymarin on sawfly (Arge pullata)-induced
hepatotoxicosis in sheep.
Author
Thamsborg SM; Jorgensen; Brummerstedt E; Bjerregard J
Address
Department of Clinical Studies, Royal Veterinary and Agricultural
University, Frederiksberg, Denmark.Source
Vet Hum Toxicol, 38(2):89-91 1996 Apr
Abstract
The prevention of hepatotoxicity from sawfly larvae (Arge pullata)
was studied in 8 lambs by using Silymarin, a botanical compound
isolated from Silybum marianum. Of 2 lambs dosed orally with
larvae only, 1 had a marked toxic response whereas the other
responded poorly as judged from clinical parameters, blood biochemistry
and pathology. Two lambs treated with penicillin, glucose and
Silymarin 7 and 24 h after larvae dosing were not affected by
toxicosis, whereas 2 lambs treated similarly but without Silymarin
responded intermediate to the other 2 groups. Our study suggests
a favorable effect using Silymarin in treatment of sawfly larvae-induced
ruminant hepatotoxicosis.
Title
The effect of Silymarin on concentration and total content of
nucleic acids in tissues of continuously irradiated rats.
Author
Haková H; Misúrová E; Kropácová
K
Address
P. J. Safárik University, Faculty of Sciences, Kosice,
Slovak Republic.
Source
Vet Med (Praha), 41(4):113-9 1996 Apr
Abstract
The effect of the hepatoprotective drug Silymarin (Flavobion)
on the radiation injury of rats continuously irradiated with
gamma rays (60Co) was studied. The rats were irradiated during
14 days by the dose rates of 0.2 and 0.6 Gy/day. In the course
of irradiation the animals were treated with Silymarin twice
daily (70 mg/kg p. o. by tube). Silymarin effect was evaluated
on the basis of quantitative changes of nucleic acids in the
regenerating liver (after 70% hepatectomy), spleen, bone marrow
and blood. Silymarin administration in the course of continuous
gamma irradiation influenced beneficially the radiation-induced
changes of DNA and RNA especially in the bone marrow.
Title
Long-term (12 months) treatment with an anti-oxidant drug (Silymarin)
is effective on hyperinsulinemia, exogenous insulin need and
malondialdehyde levels in cirrhotic diabetic patients.
Author
Velussi M; Cernigoi AM; De Monte A; Dapas F; Caffau C; Zilli
M
Address
Anti-Diabetes Centre, Monfalcone Hospital, Gorizia, Italy.
Source
J Hepatol, 26(4):871-9 1997 Apr
Abstract
BACKGROUND/AIMS: Several studies have demonstrated that diabetic
patients with cirrhosis require insulin treatment because of
insulin resistance. As chronic alcoholic liver damage is partly
due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing
agents may be useful in treating or preventing damage due to
free radicals. The aim of this study was to ascertain whether
long-term treatment with Silymarin is effective in reducing lipoperoxidation
and insulin resistance in diabetic patients with cirrhosis. METHODS:
A 12-month open, controlled study was conducted in two well-matched
groups of insulin-treated diabetics with alcoholic cirrhosis.
One group (n=30) received 600 mg Silymarin per day plus standard
therapy, while the control group (n=30) received standard therapy
alone. The efficacy parameters, measured regularly during the
study, included fasting blood glucose levels, mean daily blood
glucose levels, daily glucosuria levels, glycosylated hemoglobin
(HbA1c) and malondialdehyde levels. RESULTS: There was a significant
decrease (p<0.01) in fasting blood glucose levels, mean daily
blood glucose levels, daily glucosuria and HbA1c levels already
after 4 months of treatment in the Silymarin group. In addition,
there was a significant decrease (p<0.01) in fasting insulin
levels and mean exogenous insulin requirements in the treated
group, while the untreated group showed a significant increase
(p<0.05) in fasting insulin levels and a stabilized insulin
need. These findings are consistent with the significant decrease
(p<0.01) in basal and glucagon-stimulated C-peptide levels
in the treated group and the significant increase in both parameters
in the control group. Another interesting finding was the significant
decrease (p<0.01) in malondialdehyde/levels observed in the
treated group. CONCLUSIONS: These results show that treatment
with Silymarin may reduce the lipoperoxidation of cell membranes
and insulin resistance, significantly decreasing endogenous insulin
overproduction and the need for exogenous insulin administration.
Title
Effect of portal vein ligation and Silymarin treatment on aspirin
metabolism and disposition in rats.
Author
Favari L; Soto C; Mourelle M
Address
Departamento de Farmacologia y Toxicologia, Cinvestav-I.P.N.,
Mexico.
Source
Biopharm Drug Dispos, 18(1):53-64 1997 Jan
Abstract
The influence of portal hypertension on the metabolism and pharmacokinetics
of aspirin was evaluated after the administration of a single
oral dose of acetylsalicylic acid (20 mgkg(-1)) in portal-vein-ligated
(PVL) rats. Experiments were also performed in control (sham-operated
rats) and in rats that received an oral daily dose (150 mgkg(-1))
of Silymarin from the tenth day after surgery for 7 d. Plasma
concentration profiles of all groups exhibited monoexponential
decay but with important changes in pharmacokinetic parameters.
The aspirin elimination constant (k) for PVL rats was lower than
for control rats, whereas the plasma half-life and area under
the curve were greater than those in the control group. However,
Cmax was comparable with that of the control rats. Urinary excretion
of the metabolites (salicylic acid and glucuronides) was significantly
altered in PVL rats: the urinary glucuronides were reduced and
urinary salicylic acid was increased. The activities of plasma
and liver esterases were increased significantly in PVL rats,
while the activity of p-nitroanisole-O-demethylase was not affected.
Depletion of cytochrome P 450 was also noted in the same group
of rats. Silymarin markedly reversed the alterations found in
the PVL group.
Title
Silymarin and its components are inhibitors of beta-glucuronidase.
Author
Kim DH; Jin YH; Park JB; Kobashi K
Address
College of Pharmacy, Kyunghee University, Seoul, Korea.
Source
Biol Pharm Bull, 17(3):443-5 1994 Mar
Abstract
Silymarin, a commercial crude drug used as a hepatoprotective,
was found to inhibit 53% of beta-glucuronidase activity at a
final concentration of 0.8 mg/ml. Of three compounds A, silybin
and C, which were isolated from Silymarin, A and silybin potently
inhibited the enzyme activity, followed by C. beta-Glucuronidases
of intestinal bacteria, HGU-1 and HGU-2, and E. coli HB101 were
noncompetitively inhibited by silybin. beta-Glucuronidase of
the feces of a healthy human and of a human with colon cancer
were also inhibited by silybin, Silymarin and saccharic acid
1,4-lactone at 0.03-0.15 mg/ml. Silymarin and silybin protected
the increase in enzyme activity in the serum of the rats treated
with CCl4.
Title
Hepatoprotective mechanism of Silymarin: no evidence for involvement
of cytochrome P450 2E1.
Author
Miguez MP; Anundi I; Sainz-Pardo LA; Lindros KO
Address
Biomedical Research Center, ALKO Ltd, Helsinki, Finland.
Source
Chem Biol Interact, 91(1):51-63 1994 Apr
Abstract
The involvement of the alcohol-inducible cytochrome P450 2E1
in the hepatoprotective mechanism of the plant flavonoid extract
Silymarin, and its main active component silybin, was investigated
in isolated hepatocytes. Allyl alcohol toxicity, associated lipid
peroxidation and GSH depletion was efficiently counteracted by
Silymarin (0.01-0.5 mM), and at higher concentrations by silybin.
Cell damage by t-butyl hydroperoxide was also prevented by Silymarin
and silybin, but less efficiently. However, the covalent binding
of the acetaminophen intermediate, formed via P450 2E1, was unaffected
by addition of the flavonoids. silybin did not influence microsomal
2E1-catalyzed demethylation of N-nitrosodimethylamine. Neither
did demethylation of N-nitrosodimethylamine or aminopyrine by
isolated microsomes affect the in vivo administration of silybin.
Addition of Silymarin or silybin to primary cultures of isolated
hepatocytes did not prevent cell damage induced by exposure to
the P450 2E1 substrate CCl4. In contrast, the mere presence of
low concentrations (25-50 microM) of these compounds was found
to inhibit cell attachment to the matrix and eventually resulted
in cell damage. We conclude that contrary to earlier reports
we found no evidence for an interaction of Silymarin or silybin
with cytochrome P450 2E1. This suggests that the antioxidant
and free radical scavenging properties may account for most of
the therapeutic effect of these compounds. The untoward effect
of Silymarin on cultured cells may have consequences when considering
long-term prescription of this therapeutic agent.
Title
Hepatoprotective effect of the fractions of Ban-zhi-lian on experimental
liver injuries in rats.
Author
Lin CC; Shieh DE; Yen MH
Address
Graduate Institute of Natural Products of Kaohsiung Medical College,
Taiwan.
Source
J Ethnopharmacol, 56(3):193-200 1997 May
Abstract
The hepatoprotective effect of various fractions (n-hexane, CHCl3,
EtOAc, n-BuOH, and H2O) of Ban-zhi-lian derived from Scutellaria
rivularis Benth was studied against carbon tetrachloride (CCl4),
D-galactosamine (D-GalN) and acetaminophen (APAP)-induced acute
hepatotoxicity in rats. Liver damage was assessed by quantifying
serum activities of glutamate oxaloacetate transaminase (sGOT)
and glutamate pyruvate transaminase (sGPT), as well as by histopathological
examination. The results indicated that the CHCl3 fraction and
EtOAc fractions exhibited the greatest hepatoprotective effects
on CCl4-induced liver injuries, the CHCl3 fraction and n-hexane
fraction are most potent against D-GalN-induced intoxication,
and the CHCl3 fraction represented the most liver-protective
effect on APAP-induced hepatotoxicity. The pathological changes
of hepatic lesions caused by these three hepatotoxicants were
improved by treatment with the fractions mentioned above, which
were compared to Glycyrrhizin (GLZ) and Silymarin as standard
reference medicines.
Title
Gastroprotection induced by Silymarin, the hepatoprotective principle
of Silybum marianum in ischemia-reperfusion mucosal injury: role
of
neutrophils.
Author
AlarcÍon de la Lastra AC; MartÍin MJ; Motilva V;
JimÍenez M; La Casa C; LÍopez A
Address
Departamento de Farmacia y TecnologÍia FarmacÍeutica,
Facultad de
Farmacia, Sevilla, Spain.
Source
Planta Med, 61(2):116-9 1995 Apr
Abstract
Investigations were carried out to determine the antiulcer effects
of Silymarin, the hepatoprotective principle of Silybum marianum
L. Gaertn., in gastric injury induced by ischemia-reperfusion
and its effects on mucosal myeloperoxidase activity, an index
of polymorphonuclear leukocyte infiltration, after injury in
rats. These results were compared with those from rats that received
allopurinol, an inhibitor of xanthine oxidase and with those
from rats made neutropenic by prior administration of dexamethasone
and methotrexate. Pretreatment with Silymarin prevented post-ischemic
mucosal injury. The mean ulcer indexes (U.I.) of rats treated
with 25, 50 mg, and 100 mg Silymarin/kg body weight (4.79 +/-
0.75, 4.50 +/- 0.81, and 3.63 +/- 0.74, respectively) were significantly
lower (p < 0.05, 0.05, and p < 0.005) than that of control
rats. Allopurinol was considerably more potent in reducing the
U.I. than Silymarin, with a calculated U.I. of 2.33 +/- 0.45,
p < 0.001. These protective effects were specifically related
to a reduction in the number of neutrophils in the gastric mucosa.
Reduction in the numbers of circulating neutrophils by treating
rats with methotrexate (MPO level of 7.2 x 10(-2) +/- 0.56 x
10(-2)U/mg wt) and dexamethasone (MPO level of 6.97 x 10(-2)
+/- 0.68 x 10(-2)U/mg wt) also resulted in a significant reduction
in the susceptibility to gastric damage induced by ischemia-reperfusion.
These results suggest that neutrophils play an important role
in the gastric mucosal dysfunction associated with ischemia-reperfusion.
These findings also indicate that the inhibitory effects of Silymarin
on neutrophil function may contribute significantly to its gastroprotective
actions.
Title
Biochemical bases of the pharmacological action of the flavonoid
Silymarin and of its structural isomer silibinin.
Author
Valenzuela A; Garrido A
Address
Unidad de Bioquímica Farmacológica y Lípidos,
Universidad de Chile, Santiago.
Source
Biol Res, 27(2):105-12 1994
Abstract
The flavonoid Silymarin and one its structural components, silibinin,
have been well characterized as hepato-protective substances.
However, little is known about the biochemical mechanisms of
action of these substances. This review deals with recent investigations
to elucidate the molecular action of the flavonoid. Three levels
of action have been proposed for Silymarin in experimental animals:
a) as an antioxidant, by scavenging prooxidant free radicals
and by increasing the intracellular concentration of the tripeptide
glutathione; b) regulatory action of the cellular membrane permeability
and increase of its stability against xenobiotic injury; c) at
the nuclear expression, by increasing the synthesis of ribosomal
RNA by stimulating DNA polymerase I and by exerting a steroid-like
regulatory action on DNA transcription. The specific hepatoprotective
action of silibinin against the toxicity of ethanol, phenylhydrazine
and acetaminophen is also discussed. It is suggested that the
biochemical effects observed for the flavonoid in experimental
models may settle the basis for understanding the pharmacological
action of Silymarin and silibinin.
Title
Alcohol and liver fibrosis--pathobiochemistry and treatment.
Author
Schuppan D; Atkinson J; Ruehl M; Riecken EO
Address
Klinikum Benjamin Franklin, Abteilung für Gastroenterologie
und Hepatologie, Freie Universität, Berlin, Germany.
Source
Z Gastroenterol, 33(9):546-50 1995 Sep
Abstract
In Western societies roughly 50% of all cases of liver cirrhosis
are related to alcohol abuse. The oxidative metabolite of ethanol,
acetaldehyde, often in conjunction with viral or metabolic liver
disease, is implicated as the major cause for liver fibrogenesis.
Acetaldehyde damages cell membranes, initiates lipid peroxidation
and forms noxious protein adducts, resulting in the activation
of Kupffer cells and perisinusoidal lipocytes/portal fibroblasts.
The activation of lipocytes and fibroblasts to a proliferative
and collagen-producing myofibroblast-like phenotype is triggered
by the release of fibrogenic factors such as platelet-derived
growth factor (PDGF) and transforming growth factor-beta (TGF-beta)
from the activated Kupffer cells. Due to the socioeconomic burden
inflicted by cirrhosis, antifibrotic treatment is urgently needed.
Strategies to prevent or reverse cirrhosis must interrupt the
continuous process of pathological wound healing in the liver.
An antifibrotic effect has been demonstrated for the interferons,
prostaglandins E and relaxin. Polyunsaturated lecithin, Silymarin
and ursodeoxycholic acid, agents with a high hepatotropism and
a good safety-profile, appear to have antifibrotic properties.
Targeted approaches include the specific removal of matrix-bound
fibrogenic growth factors and the induction of stress-relaxation
of the activated mesenchymal cells by biologically active matrix-peptides
and their stable analogues. Since serum tests for the non-invasive
assessment of collagen synthesis and degradation in the liver
are now available, rapid progress in the development and clinical
application of antifibrotic drugs can be anticipated. |
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