|
Title
Author
Pietrangelo A; Borella F; Casalgrandi G; Montosi G; Ceccarelli
D; Gallesi D; Giovannini F; Gasparetto A; Masini A
Address
Dipartimento di Medicina Interna, University of Modena, Italy.
Source
Gastroenterology, 109(6):1941-9 1995 Dec
Abstract
BACKGROUND & AIMS: Hepatic iron toxicity may be mediated
by free radical species and lipid peroxidation of biological
membranes. The antioxidant property of silybin, a main constituent
of natural flavonoids, was investigated in vivo during experimental
iron overload. METHODS: Rats were fed a 2.5% carbonyl-iron diet
and 100 mg.kg body wt-1.day-1 silybin for 4 months and were assayed
for accumulation of hepatic lipid peroxidation by-products by
immunocytochemistry, mitochondrial energy-dependent functions,
and mitochondrial malondialdehyde content. RESULTS: Iron overload
caused a dramatic accumulation of malondialdehyde-protein adducts
into iron-filled periportal hepatocytes that was decreased appreciably
by silybin treatment. The same beneficial effect of silybin was
found on the iron-induced accumulation of malondialdehyde in
mitochondria. As to the liver functional efficiency, mitochondrial
energy wasting and tissue adenosine triphosphate depletion induced
by iron overload were successfully counteracted by silybin. CONCLUSIONS:
Oral administration of silybin protects against iron-induced
hepatic toxicity in vivo. This effect seems to be caused by the
prominent antioxidant activity of this compound.
Title
Inhibition of rat liver cytosolic glutathione S-transferase by
silybin.
Author
Bartholomaeus AR; Bolton R; Ahokas JT
Address
Key Centre for Applied and Nutritional Toxicology, RMIT-University,
Melbourne, Australia.
Source
Xenobiotica, 24(1):17-24 1994 Jan
Abstract
1. The naturally occurring hepatoprotective compound silybin
is a potent inhibitor of glutathione S-transferase isoenzymes
1-1, 2-2, 3-3, and 4-4, displaying a high degree of isoenzyme
selectivity. 2. Using CDNB at a fixed concentration of 1 mM and
varying the GSH concentration, silybin exhibited competitive
inhibition of isoenzyme 2-2 with a Ki of 32 microM, non-competitive
and predominantly non-competitive inhibition of isoenzymes 1-1
and 4-4 with Kis of 20 and 1.2 microM, respectively, and uncompetitive
inhibition of isoenzyme 3-3 with a Ki of 0.2 microM. 3. With
CDNB as the variable concentration substrate silybin exhibited
competitive inhibition of isoenzyme 1-1 with a Ki of 8 microM,
non-competitive inhibition of isoenzyme 2-2 with a Ki of 41 microM,
and non-competitive inhibition of isoenzymes 3-3 and 4-4 with
Kis of 0.8 and 0.5 microM, respectively.
Title
Spontaneous regression of hepatocellular carcinoma [see comments]
Author
Grossmann M; Hoermann R; Weiss M; Jauch KW; Oertel H; Staebler
A; Mann K; Engelhardt D
Address
Department of Medicine II, Klinikum Grosshadern, University of
Munich, Germany.
Source
Am J Gastroenterol, 90(9):1500-3 1995 Sep
Abstract
Spontaneous regression of cancer is a rare phenomenon seldom
described in patients with hepatocellular carcinoma. A case of
spontaneous regression of hepatocellular carcinoma is reported
and compared with the reports published in the English literature.
A 52-yr-old man presented with biopsy-proven hepatocellular carcinoma,
which was considered to be unresectable at initial laparotomy.
The tumor subsequently regressed without specific treatment,
as assessed radiologically and by normalization of a previously
elevated alpha-fetoprotein level. At repeat laparotomy 14 months
after initial diagnosis, intraoperative ultrasound failed to
disclose a hepatic mass, and multiple biopsies showed no evidence
of malignancy. To date, only nine case reports of apparently
spontaneous regression of hepatocellular carcinoma have been
published in the English literature. Clinical characteristics
discriminating these patients from less fortunate patients with
hepatocellular carcinoma could not be identified. The mechanisms
underlying this intriguing phenomenon remain unknown.
Title
Scavenging effect of silipide, a new silybin-phospholipid complex,
on ethanol-derived free radicals.
Author
Comoglio A; Tomasi A; Malandrino S; Poli G; Albano E
Address
Department of Experimental Medicine and Oncology, University
of Torino, Italy.
Source
Biochem Pharmacol, 50(8):1313-6 1995 Oct 12
Abstract
Ethanol metabolism by cytochrome P4502E1 (CYP2E1) produces free
radical intermediates, identified as hydroxyethyl radicals. We
have observed that in vitro addition or in vivo pretreatment
of rats with Silipide, a new 1:1 complex of silybin with phosphatidyl-choline,
is able to decrease the spin trapping of hydroxyethyl radicals
in microsomes from chronic alcohol-fed rats. This effect is not
due to an interference with the metabolism of ethanol by CYP2E1,
but is rather related to the capacity of the silybin molecule
to scavenge hydroxyethyl radicals. However, such an effect is
lost when pure silybin in amounts comparable to those present
in Silipide is administered instead, due to the low bioavailability
of uncomplexed flavonoid. Further experiments in vivo have shown
that Silipide administration also decreases hydroxyethyl radical
signals detectable in the bile of rats acutely treated with ethanol.
The ability of Silipide to scavenge ethanol-derived radicals
along with its antioxidant activity suggests that this drug might
be potentially useful in counteracting free radical-mediated
injuries involved in the development of liver damage caused by
alcohol abuse.
Title
The effect of dietary flavonoids on DNA damage (strand breaks
and oxidised pyrimdines) and growth in human cells.
Author
Duthie SJ; Johnson W; Dobson VL
Address
Rowett Research Institute, Bucksburn, Aberdeen, UK.
Source
Mutat Res, 390(1-2):141-51 1997 Apr 24
Abstract
The effects of the flavonoids quercetin, myricetin and Silymarin
on DNA damage and cytotoxicity in human cells were investigated.
DNA strand breaks and oxidised pyrimidines were determined using
alkaline single cell gel electrophoresis (the comet assay). Inhibition
of cell growth was also measured. Caco-2 (colon), HepG2 (liver),
HeLa (epithelial) cells and normal human lymphocytes showed different,
dose-dependent susceptibilities (in terms of strand breakage)
to the various flavonoids, quercetin being the most damaging.
This agreed well with the ability of the flavonoids to inhibit
cell growth. None of the flavonoids induced DNA base oxidation
above background levels. All of the flavonoids under investigation
caused depletion of reduced glutathione, which, in the case of
quercetin, occurred prior to cell death. Neither cytotoxicity
nor genotoxicity was associated with the antioxidant enzyme capacity
(glutathione, glutathione reductase, glutathione peroxidase and
catalase) of the cells.
Title
Scavenging of reactive oxygen species by silibinin dihemisuccinate.
Author
Mira L; Silva M; Manso CF
Address
Instituto de QuÍimica FisiolÍogica, Faculdade de
Medicina de Lisboa, Portugal.
Source
Biochem Pharmacol, 48(4):753-9 1994 Aug 17
Abstract
Silibinin dihemisuccinate (SDH) is a flavonoid of plant origin
with hepatoprotective effects which have been partially attributed
to its ability to scavenge oxygen free radicals. In the present
paper the antioxidant properties of SDH were evaluated by studying
the ability of this drug to react with relevant biological oxidants
such as superoxide anion radical (O2-), hydrogen peroxide (H2O2),
hydroxyl radical (HO.) and hypochlorous acid (HOCl). In addition,
its effect on lipid peroxidation was investigated. SDH is not
a good scavenger of O2- and no reaction with H2O2 was detected
within the sensitivity limit of our assay. However, it reacts
rapidly with HO. radicals in free solution at approximately diffusion-controlled
rate (K = (1.0-1.2) x 10(10)/M/sec) and appears to be a weak
iron ion chelator. SDH at concentrations in the micromolar range
protected alpha 1-antiproteinase against inactivation by HOCl,
showing that it is a potent scavenger of this oxidizing species.
Luminol-dependent chemiluminescence induced by HOCl was also
inhibited by SDH. The reaction of SDH with HOCl was monitored
by the modification of the UV-visible spectrum of SDH. The studies
on rat liver microsome lipid peroxidation induced by Fe(III)/ascorbate
showed that SDH has an inhibitory effect, which is dependent
on its concentration and the magnitude of lipid peroxidation.
This work supports the reactive oxygen species scavenger action
ascribed to SDH.
Title
The hepatoprotective and cholagogic action of glycyrrhizic acid
derivatives]
Author
Nasyrov KhM; Chepurina LS; Kireeva RM
Source
Eksp Klin Farmakol, 58(6):60-3 1995 Nov-Dec
Abstract
The experiments on rats with toxic hepatic damage induced by
tetrachloromethane have shown that the derivatives of glycyrrhizinic
acid (5NGA) promote a decrease in the rate of lipid peroxide
oxygenation in the hepatic tissue homogenate and the blood serum,
in the inhibition of organospecific enzyme activity (BHMT, ALT,
AST) and increase in choleresis. The data obtained testify to
the hepatoprotective activity of the derivatives of glycyrrhizinic
acid.
Title
Hepatoprotective activity of xanthones and xanthonolignoids against
tert-butylhydroperoxide-induced toxicity in isolated rat hepatocytes--comparison
with silybin.
Author
Fernandes ER; Carvalho FD; Remião FG; Bastos ML; Pinto
MM; Gottlieb OR
Address
C.E.Q.O.F.F.U.P., Faculdade de Farmácia, Universidade
do Porto,
Portugal.
Source
Pharm Res, 12(11):1756-60 1995 Nov
Abstract
PURPOSE. Synthesize and evaluate the protective activity against
tertbutylhydroperoxide-induced toxicity in freshly isolated rat
hepatocytes of trans-kielcorin, trans-isokielcorin B, as well
as their respective building blocks 3,4-dihydroxy-2-methoxyxanthone
and 2,3-dihydroxy-4-methoxyxanthone. METHODS. Wistar rats, weighing
200-250g were used. Hepatocyte isolation was performed by collagenase
perfusion. Incubations were performed at 37 degrees C, using
1 million cells per milliliter in modified Krebs--Henseleit buffer.
The protective activity was evaluated by measuring reduced and
oxidized glutathione, lipid peroxidation and cell viability after
inducing toxicity with tert-butylhydroperoxide (1.0 mM, 30 min),
with or without the studied compounds in the concentrations of
0.025, 0.050, 0.100 and 0.200 mM. silybin was tested in the same
experimental conditions to serve as a positive control. RESULTS.
Using these concentrations, the tested compounds prevented tert-butylhydroperoxide-induced
lipid peroxidation and cell death in freshly isolated rat hepatocytes.
All compounds were also effective in preventing perturbation
of cell glutathione homeostasis in some extent. 3,4-Dihydroxy-2-methoxyxanthone
and 2,3-dihydroxy-4-methoxyxanthone were more effective than
trans-kielcorin and trans-isokielcorin B respectively. silybin
was less effective in protecting cells against lipid peroxidation
and loss of cell viability than the four xanthonic derivatives.
CONCLUSIONS. The tested compounds protected the freshly isolated
rat hepatocytes against tert-butylhydroperoxide-induced toxicity.
Title
Free radical scavenging and antioxidative properties of 'silibin'
complexes on microsomal lipid peroxidation.
Author
Basaga H; Poli G; Tekkaya C; Aras I
Address
Department of Food Engineering, Middle East Technical University,
Ankara, Turkey. basaga@boun.edu.tr
Source
Cell Biochem Funct, 15(1):27-33 1997 Mar
Abstract
The antioxidant properties of silibin complexes, the water-soluble
form silibin dihemisuccinate (SDH), and the lipid-soluble form,
silibin phosphatidylcholine complex known as IdB 1016, were evaluated
by studying their abilities to react with the superoxide radical
anion (O2-.), and the hydroxyl radical (OH.). In addition, their
effect on pulmonary and hepatic microsomal lipid peroxidation
had been investigated. Superoxide radicals were generated by
the PMS-NADH system and measured by their ability to reduce NBT.
IC50 concentrations for the inhibition of the NBT reduction by
SDH and IdB 1016 were found to be 25 microM and 316 microM respectively.
Both silibin complexes had an inhibitory effect on xanthine oxidase
activity. SDH reacted rapidly with OH radicals at approximately
diffusion controlled rate and the rate constant was found to
be (K = 8.2 x 10(9) M-1 s-1); it appeared to chelate Fe2+ in
solution. In hepatic microsomes, when lipid peroxidation was
induced by Fe2+, SDH inhibited by 39.5 per cent and IdB 1016
by 19.5 per cent, whereas when lipid peroxidation was induced
by CuOOH, IdB 1016 exerted a better protective effect than SDH
(29.4 per cent and 19.4 per cent inhibition, respectively). In
both microsomal systems lipid peroxidation proceeded through
a thiol depletion mechanism which could be restored in the presence
of silibin complexes. Low levels of lipid peroxidation in pulmonary
microsomes point out the differences between in-vitro lipid peroxidation
occurring in microsomes of different tissues. The results support
the free radical scavenger and antioxidative properties of silibin
when it is complexed with a suitable molecule to increase its
bioavailability.
Title
The hepatoprotective effects of Taiwan folk medicine ham-hong-chho
in rats.
Author
Chin HW; Lin CC; Tang KS
Address
Foo Yin College of Nursing & Medical Technology, Kaohsiung,
Taiwan.
Source
Am J Chin Med, 24(3-4):231-40 1996
Abstract
Bidens pilosa L. var minor (Blume) Sherff, B. pilosa L. and B.
chilensis DC (compositae), commonly known as "Ham-hong-chho"
in Taiwan, have been traditionally used for medicinal purposes.
To clarify and compare the hepatoprotective effects of these
three plants, we evaluated their potential effectiveness on CCl4-
and acetaminophen-induced acute hepatic lesions in rats. The
results indicated that the increase in SGOT and SGPT activities
caused by CCl4 (3.0 ml/kg, s.c.) and acetaminophen administration
(600 mg/kg, i.p.) could be significantly reduced by treating
with the extracts of all the three kinds of "Ham-hong-chho"
and the extract of B. chilensis exhibited the greatest hepatoprotective
effects. These phenomena were also confirmed by histological
observation. Liver damage induced by CCl4 and acetaminophen was
markedly improved in the extract of B. chilensis treated groups,
while groups treated with the extracts of B. pilosa var minor
and B. pilosa demonstrated only moderate protective effects.
The pharmacological and pathological effects of these three crude
groups were compared with Bupleurum chinense, which has been
reported previously as a treatment criteria in the CCl4 model,
and with Silymarin as a standard reference medicine in the acetaminophen
model. The results suggest that B. pilosa var minor, B. pilosa
and B. chilensis can protect liver injuries from various hepatotoxins
and have potential as broad spectrum antihepatic agents.
Title
Synthesis and antihepatotoxic activity of silybin 11-O-phosphate.
Author
Pifferi G; Pace R; Conti M
Address
Istituto di Chimica Farmaceutica e Tossicologia, UniversitÍa
di Milano, Italy.
Source
Farmaco, 49(1):75-6 1994 Jan
Abstract
silybin 11-O-phosphate 3 was synthesized by selective phosphorylation
of silybin with POCl3. The pharmacological activity of 3 was
evaluated in the rat by using the praseodymium poisoning test.
Preliminary results showed that the compound possesses antihepatotoxic
activity, possibly with lower potency compared to the reference
drug silybin hemisuccinate.
Title
Scavenging of reactive oxygen species and inhibition of arachidonic
acid metabolism by silibinin in human cells.
Author
Dehmlow C; Murawski N; de Groot H
Address
Institut für Physiologische Chemie, Universitätsklinikum,
Essen,
Germany.
Source
Life Sci, 58(18):1591-600 1996
Abstract
The effects of the flavonoid silibinin, which is used for the
treatment of liver diseases, on the formation of reactive oxygen
species and eicosanoids by human platelets, white blood and endothelial
cells were studied. Silibinin proved to be a strong scavenger
of HOCI (IC50 7 microM), but not of O2- (IC50 > 200 microM)
produced by human granulocytes. The formation of leukotrienes
via the 5-lipoxygenase pathway was strongly inhibited. In human
granulocytes IC50-values of 15 microM and 14.5 microM silibinin
were detected for LTB4 and LTC4/D4/E4/F4 formation, respectively.
In contrast to this, three- to fourfold silibinin concentrations
were necessary to half maximally inhibit the cyclooxygenase pathway.
For PGE2 formation by human monocytes an IC50-value of 45 microM
silibinin was found. IC50-values of 69 microM and 52 microM silibinin
were determined for the inhibition of TXB2 formation by human
thrombocytes and of 6-K-PGF1 alpha formation by human omentum
endothelial cells, respectively. Thus, the deleterious effects
of HOCI that can lead to cell death, and those of leukotrienes
that are especially important in inflammatory reactions, can
be inhibited by silibinin in concentrations that are reached
in vivo after the usual clinical dose. Silibinin is thought not
only to display hepatoprotective properties but might also be
cytoprotective in other organs and tissues. |
|
Return to Main Page
