Screening Methods for
Hepatoprotective Agents in Experimental Animal’s
Nimbalkar V.V.*, Pansare P.M.,
Nishane B.B.
Department of Pharmacology, P.D.V.V.P.F’s College of Pharmacy, Vilad Ghat, Post: MIDC,
Ahmednagar, Maharashtra, India.414111
*Corresponding Author E-mail: rajevikram@gmail.com
ABSTRACT:
Hepatic disease is term for
a collection of conditions disease and infection that affect the cells,
tissues, structure or functions of the liver.liver has a wide range of function
,including detoxification, protein
synthesis , and production of biochemical necessary for digestion and synthesis
as well as breakdown of small and
complex, many of which are necessary for normal vital function .
Both
in-vitro and in-vivo liver models have been develops in the past year two study
the hepatoprotective agents. These
system majors the ability of the test drug to prevent or cure liver toxicity
(Induced by hepatotoxin) in experimental animals. In in-vitro model fresh
hepatocytes are treated with hepatotoxin and the effect of the test drug on the
same in evaluation .In in –vivo models, a toxic dose or repeated doses of a
known hepatotoxinare administrated to induce liver damage in experimental
animals. The test substance administrated along, with prior to and/ or after
the toxin treatment. Various chemical agents normally used to induce hepatotoxicity
in experimental animal for the evaluation hepatoprotective agents include
carbon tetrachloride, paracetamol, Acryilamide, adrimacyin, alcohol
antituburcularetc. These explain the mechanism of action of various hepatotoxic
chemical drugs, their doses and routes of administration.
KEYWORDS: Silymarin,
Paracetamol, Feroussulphate, Ethanol etc.
INTRODUCTION :( 1)
Herbal
medicines have been of tremendous interest since the beginning of human
civilization for the treatment of all kinds of ailments. Following the advent
of modern medicines herbal preparations suffered a serious setback. During the
last couple of decades, however, advances in photochemistry and in
identification of plant products-effective against certain diseases-have
rekindled the interest. Indeed the plant kingdom has been the therapeutic
arsenal of all documented traditional systems of medicine. Liver diseases
remain one of the serious health problems. In the absence of reliable liver
protective drugs in allopathic medicinal practices, herbs play a role in the
management of various liver disorders.
Numerous
medicinal plants and their formulations are used for liver disorders in ethno
medical practices as well as in traditional systems of medicine in India. Liver
disease appears to be on the increase. Part of this increase may be due to our
frequent contact with chemicals and other environment pollutants. The amount of
medicine consumed has increased greatly with resulting dangers to the liver.
The
liver, the detoxifying factory in the body, has become an increasingly
overworked organ. While those who smoke, abuse alcohol and drugs, and live in
severely polluted environments are at greatest risk, we all suffer from threat
of liver. Reducing the consumption of alcohol, mixing drugs or taking
unnecessary drugs and consulting a physician if there are sign or symptoms of
liver disease can prevent damage to the liver. Prevention also includes
maintaining a balanced diet that includes nutrients and herbs that support a
healthy liver. Problems associated with liver dysfunction can ultimately lead
to serious illness such as hepatitis, cirrhosis, fatty liver, alcoholic liver
disease, and biliary cirrhosis. Millions of Americans are afflicted with liver
disease, with over 43,000 deaths each year and hospitalization costs greater
than 7 billion dollars.
EXPERIMENTAL
MODELS:
Carbon
tetrachloride induced hepatotoxicity in rats:
Mechanism of action:
CCl4
is widely used experimentally as hepatotoxic which is bio transformed by the
cytochrome p-450 system to produce the trichloormethyl free radical which in
turn covalently binds to cell membrane and organelles to elicit lipid
peroxidation disturbs calcium hemostasis and finally results in death of cell.
Lipid peroxidation is a complex and natural deleterious process. The
significant increase observed in levels of lipid peroxides in liver of CCL4
intoxicated shows free radical induced liver damage.(2) The
hepatotoxic effect of CCl4 results in intense centrilobular necrosis
and vacuolization with significant no of swollen hepatocytes which ultimately
leads to accumulation of fat in liver and kidney. Fatty degeneration was also
observed in centrilobular areas. The AST, ALT and ALP are found higher in
concentration in cytoplasm, when the liver cell membrane damaged by CCl4 administration,
these enzymes which are normally located in cytosols’ are released into the
blood stream. AS Twill be released into the cytosol also by the injury of the
organelles such as mitochondria. The activity of these enzymes in serum is
useful quantitative marker of the extent and type of hepatocellular damage. The
elevation of alkaline phosphatase in serum due to toxic effect of CCl4 is
the result of defective excretion of bile by the liver. This ALP activity is
related to functioning of hepatocytes. Increase in its activity is due to the
increase synthesis in presence of increase biliary pressure. (3) The
increased level of serum bilirubin is conventional indicator of liver injury.
One of the most important distinguishing features observed in experimental
hepatic damage is the pronounced depression in the level of serum total
protein. It is evident that CCL4 poisoning leads to cessation of
movement of large amount of triglycerides from the liver to the plasma. So the
lipid profile of CCl4 intoxicated group showed considerable degree
of elevation in the concentration of serum, total lipid, cholesterol and
triglycerides. Also the above parameters were increased in the tissue such
liver, kidney, heart and lungs.
The
injury and dysfunction of liver caused by the toxic effect of CCl4 in
experimental animals simulated the human viral hepatitis model. In CCl4 induced
toxic hepatitis a toxic reactive metabolite trichloro methyl radical was
produced by the microsomal oxidase system. These activated radicals bind
covalently to macromolecules of the lipid membrane of endoplasmic reticulum and
causes peroxidative degradation of lipids. As a result fats from the adipose
tissues weretranslocated and accumulated in the liver. The estimation of total
bilirubin confirms the intensity of jaundice. In viral and toxic hepatitis the
degree of excretion of bilirubin from the intestine is very less and bilirubin
present in the liver is excreted into the canaliculated and then Regurgitated
into the blood stream. Hence hyperbilirubinemia is most common in hepatitis
patients. It is also known that liver synthesizes number of proteins. The
change in serum protein level forms the bases for important laboratory aids to
diagnose the depth of jaundice. (4) Hepatocellular necrosis leads to
very high level of AST and ALT released from the liver in blood. Between the
two ALT is better index of liver injury as live ALT activity represents 90% of
total enzyme present in the body.
Table No.1. Experimental
Protocol (Grouping, Treatment and Observations)
|
Sr.No |
Group (N=6) |
Treatment and Dose\Day |
Observation |
|
I.
|
Normal control |
Control (Distilled water
p.o) |
1) Biochemical parameter on
8 th Day. 2) Histopathological examination
on 8th day. |
|
II. |
Negative
control |
CCl4
(0.7ml\kgsc. Alternate days) |
|
|
III.
|
Positive control |
CCl4
(0.7ml\kgsc. Alternate days )+
Siymarin (100mg\kg) p.o from day 1to day 7 o.d |
|
|
IV.
|
Test Drug (25 mg/kg). |
CCl4 (0.7ml\kg
sc. Alternate days) + Test Drugp.o from day 1 to day 7 o.d |
|
|
V.
|
Test Drug (50 mg/kg). |
CCl4 (0.7ml\kg
sc. Alternate days) + Test Drugp.o from day 1 to day 7 o.d |
|
|
VI.
|
Test Drug (100mg/kg) |
CCl4 (0.7ml\kg
sc. Alternate days) + Test drug (100 ml\kg) p.o from day 1 to day 7 o.d |
Paracetamol
induced hepatotoxicity in rats:
Mechanism
of action:
Paracetamol
(N-acetyl p-amino phenol or acetaminophen) is well known antipyretic and
analgesic which produces hepatic necrosis at higher doses. Indiscriminate
ingestion can lead to accidental poisoning and potentially lethal
hepatotoxicity. Paracetamol is mainly metabolizes by glucoronide and sulphate conjugation.
A small amount is metabolized by the cytochrome P-450 system toa toxic
metabolite. The cell is normally protected from injury by conjugation of this
toxic metabolite with glutathione. As a dose increases the glutathione content
of hepatocytes available for detoxification of the toxic metabolite is
exhausted and the hepatocytes become vulnerable to the noxious effects of the
metabolite resulting in liver cell necrosis.(5) Liver is the organ
highly affected primarily by toxic agents. Paracetamol produces wide areas of
frank necrosis of liver parenchyma and a picture of dilated vasculature and
sinusoids around the necrotic zones.(6)
Paracetamol produces hepatic necrosis in high doses by covalent
binding of its toxic metabolite N-acetyl-p-benzoquinone imine to sulphadryl
groups of protein resulting in cell necrosis through lipid peroxidation induced
by decreasing glutathione in the liver. Damage to the structural integrity of
liver is reflected by an increasing in levels of serum transaminases because
they are cytoplasmic in location and are release into the circulation after
cellular damage. Free radicals cause damage in biological systems this in turn
cause cellular damage that may lead to cancer, liver injury, heart disease etc.(7)
the toxicity is medicated by a metabolite imidazole which binds
covalently in endoplasmic and in protein of cytoplasm.
Fig. 1. Mode of action of
hepatotoxicity caused by paracetamol
Table No.2. Experimental
Protocol (Grouping, Treatment and Observations)
|
Sr.no |
Group (N=6) |
Treatment and Dose/Day |
Observation |
|
I.
|
Normal control |
Control (distilled water
p.o |
1)Biochemical parameter on 3rd and 14th day. 2)Function parameter on 14th day. 3)Morphological parameter on 14th day. 4)Histopathological examination on 14th day. |
|
II.
|
Negative control |
Paracetmol (1g/kg) p.o till
day 8 |
|
|
III.
|
Positive control |
Paracetmol (1g/kg) p.o till
day 8 +Silymarin (100mg/kg) p.o from day 4 to day 13 o.d |
|
|
IV.
|
Test Drug (25 mg/ml) |
Paracetmol (1g/kg) p.o till
day 8 + Test Drug p. o from day to day 13 o.d |
Ferrous sulphate induced
hepatotoxicity in rats:
Mechanism of action:
Iron toxicity results when too much iron is injected
or less often when too much is given orally. Iron overload is associated with
liver damage, characterized by massive Iron deposition in hepatic parenchymal
cells, leading fibrosis and eventually, to Hepatic necrosis. (8)
Lipid peroxidation (LPO) had been proposed to be the major factor in iron
Toxicity, including iron induced hepatotoxicity.
A ferrous salt reacts with hydrogen peroxide derived
by the action of the Superoxide anion radical, to form the highly reactive
radical hydroxyl (Fenton Reaction) hydroxyl ion attacks all biological
molecules, including cell membrane Lipids, to initiate LPO. The highly toxic
per oxidative metabolite induces widespread cellular injury .and the leakage of
cellular enzymes into the Bloodstream, results in the augmented damage and
dysfunction.(9) Histologicallythe iron produced perioral necrosis.
Fig.2Mode of action
ferrous sulphate induced hepatoxicity
Table No.3. Experimental
Protocol (Grouping, Treatment and Observations)
|
Sr.no |
Group ( N=6) |
Treatment and Dose/Day |
Observation |
|
I.
|
Normal control |
Control (distilled water
p.o) |
1) Biochemical parameter on 10th
day. 2) Histopathological examination
on 10th day. |
|
II.
|
Negative control |
Control (distilled water
p.o) for 9 days )+Ferroussulphate (30mg/kg) i.p. on day 10 |
|
|
III.
|
Positive control |
Ferroussulphate (30mg/kg)
i.p. on day 10+ Silymarin (100mg/kg) p.o from day1 to day 9o.d |
|
|
IV.
|
Test Drug (25 mg/kg) |
Ferroussulphate (30mg/kg)
i.p. on day 10+ Test Drugp.o from day 1 to day 9 o.d |
Ethanol
induced hepatotoxicity in rat:
Mechanism
of action:
Liver
being the major site for detoxification is the primary target for environmental
or occupational toxic exposure. The alcoholic liver injury appears to be
generated by the effects of ethanol metabolism and toxic effect of
acetaldehyde, which may be mediated by acetaldehyde, altered protein. (10)
The
oxidation of ethanol via the alcohol dehydrogenase pathway results in the
production of acetaldehyde with loss of hydrogen ions. NAD (Nicotinamide Adenine
dinucleotide) is reduced to NADH. The large amounts of reducing equivalents
generated the hepatocytes ability to maintain redox homeostasis and number of
disorders as hyper uremia, hyper lipemia, and rise in HDL. The rise in NADH
promotes fatty acid synthesis as a net result hepatic fat accumulation. An ethanol
inducible form of cytochrome P-450 called 2E1 not only catalyzes ethanol
oxidation but also capable of activating various other compounds to highly
toxic metabolites. The proliferation of endoplasmic reticulum associated with
P-450 E1induction is also accompanied by enhance activity of other cytochrome
P-450s, resulting in accelerated metabolism and tolerance to other drugs as
well as increase degradation of retinal and its hepatic depletion. Also chronic
ethanol consumption results in hepatic vitamin A depletion. Ethanol oxidation,
whether by the ADH or the microsomal path way resulting acetaldehyde, which may
cause ubiquitous damage including in the mitochondria. Chronic ethanol
treatment causes 10-fold increase in splanchnic acetaldehyde release in the
hepatic vein, associated with a raking leakage of mitochondrial enzyme glutamic
dehydrogenase in to the hepatic venous blood.
One
mechanism of hepatotoxicity of acetaldehyde is its high chemical reactivityAnd
formation of adducts with various protein
Fig.3.Interaction of
direct toxicity of ethanol.
Acetaldehyde
binding shown to impair microtubule polymerization and hepatic protein
secretion together with an increase in constituent protein resulted in protein
accumulation and hepatocytes swelling explaining the ballooning of the
hepatocytes and the hepatomegaly, to characteristic features of alcohol induced
liver injury. Acetaldehyde also contributes the depletion of glutathione and
its potentiation of lipid peroxidation. After chronic alcohol consumption the
fibroblasts identified in normal liver proliferates and stellate cells (also
called lymphocytes or fat storing cells) where found to be transformed or
activated to “transitional” my fibroblast like cells associated with active
fibro genesis. Chronic alcohol intake is known to produce hypercholesterolemia,
hyperlipidemia, and hypertriglyceridemia, (11)in chronic lipid
accumulation the liver cells become fibrotic and lead to impaired liver
function. Enhanced lipid peroxidation had been reported in hyperlipidemia
induced by ethanol. Ethanol increases triglycerides and cholesterol levels thus
inducing imbalance in lipid metabolism in liver, heart, kidney and other organs
and this could explain the reason for the increase in lipid peroxidation in
these organs. It has been proven that hyperlipidemia and elevated lipid
peroxidation are interrelated. Increase in serum triglycerides in alcohol
treated rats may be due to decrease activity of lipoprotein lipase, which is
involved, in the uptake of triglycerides rich lipoprotein by extra hepatic
tissue. Increase the synthesis or decreased lipid deposition or both resulted
in simultaneous accumulation of lipids in blood and liver. Ethanol induces
hyperlipidemia and hyperlipidemia enhances lipid peroxidation causing
hepatotoxicity by increasing free radical formation which in turn increases the
level of lipid peroxides in hepatic tissue. Glutathione protects the
hepatocytes by combining with the reactive metabolites and preventing their
covalent binding to liver protein. Liver glutathione after alcohol
administration was found to decrease due to increase \ utilization by the
hepatocytes because GSH seems to act as scavengers for toxic chemical agents.
The non-availability of glutathione decreases the activity of glutathione
peroxidase and glutathione transferees. Glutathione act as substrate for both
GSH-Px and GST. Depletion of glutathione will render the enzymes (GSH-Px and
GST) in active or less active.
Fig.3 Hepatic, nutritional
and metabolic abnormalities after ethanol abuse.
Ethanol
is currently recognized as the most prevalent known cause of abnormal human
development. Chronic alcohol intake is known to produce hepatocellular damage.
Recently it was reported that high dose of ethanol impair hepatic
microcirculation by producing endothelin-1. Ethanol induced hepatic hypoxia
also been involved as a possible cause of the potentiation of hepatotoxicity.
(12) Chronic ethanol ingestion produces fatty liver, hepatomegaly,
alcoholic hepatitis, Fibrosis and cirrhosis. Indeed, steatosis due to ethanol
exposure, which was localized in cetrilobuler areas in males and pent lobular
in females. Ethanol elevates the serum AST levels and steatosis, inflammation, necrosis
assessed histologically develop more rapidly and more severe in females than
males. One mechanism of ethanol hepatotoxicity is free radical formation. Four
week of eternal ethanol treatment increases plasma endotoxin level in portal
vein significantly.
Table No.4.Experimental Protocol (Grouping, Treatment
andObservations)
|
Sr.No |
Group (N=6) |
Treatment and Dose\day. |
Observation |
|
1 |
Normal control |
1% Gum acacia in water |
1) Biochemical parameter on
22 day. 2) Morphological parameter
on 22 day. 3) Histopathological
examination on 22 day. |
|
2 |
Negative control |
CML 3ml\100gm bd.wt/day in
two divided doses for 21 days. |
|
|
3 |
Positive control |
CML 3ml\100gm bd.wt/day in
two divided doses for 21 days. +Silymarin (100mg/kg) p.o for 21 days o.d |
|
|
4 |
Test Drug) (25 mg/kg) |
CML 3ml\100gm bd.wt./day in
two divided doses for 21 days + Test Drugp.o for 21 days o.d |
D-galactosamine induced
hepatotoxicity in mice:
Mechanism of action:
The
histopathology of the liver gives the evidence for the protection imparted by
the herbal mixture and Silymarin. The metabolites of -Dgalactosamine (GaIN),
uridiophosphogalactos amine may deplete several uracil nucleotides such as
UDP-lactose, UDP-glucose and UTP, causing reduction of mRNA and glycoprotein
synthesis (i.e. reduction of ATP and glycogen synthesis), which leads to
cellular membranes alteration. (13) Nevertheless there is increasing
evidence that GaIN causes production of free hydroxyl radical leading to lipid
peroxidation. Also the levels of SOD, CAT, GPx are also concomitantly reduced.
(14)Ultimately the cellular damage and the inflammation caused by GaIN
are similar to the histopathological features of viral hepatitis in humans. (15)
This phenomenon may lead to cellular damage and cellular inflammation resulting
in histological and biochemical picture closely resembling viral hepatitis. The
Ca++homeostasis perturbation, inhibition of oxidative of NADPH and FADH
substrate at the dehydrogenase co enzyme level(16) are also
considered to be responsible for pathogenesis of GaIN induced hepatitis. PS is
co administered with GaIN by certain investigators. These leads to the release
of TNF from the macrophages and Kuffer cells. This cytokine has been firmly
implicated as an important causative mediator in the pathogenesis of alcoholic
liver diseases and hepatitis. Nevertheless TNF too has positive roles it is
responsible for the normal proliferation of the hepatocytes, but in
pathological condition it acts as panoptic agent.
Gain
caused hepatitis can be recovered by;
1 Protein
synthesis enhancement
2 Galactosamine
liver uptake inhibition
3 RES
activation
4 Renormalization
of the changed Ca++homeostasis
Table No 5. Experimental Protocol (Grouping, Treatment
and Observations)
|
Sr.No |
Group (N=6) |
Treatment and Dose\day. |
Observations |
|
1 |
Normal control |
Control (distilled water
p.o) |
1)Biochemical parameter on 2th
and 9th day. 2) Histopathological examination
on 9th day. |
|
2 |
Negative control |
D-galactosamine (800mg/kg)
i.p on day 1 o.d +Distilled Water p.o form day 2 to day 8. |
|
|
3 |
Positive control |
D-galactosamine (800mg/kg)
i.p on day 1 o.d + Livfit(50mg/kg) p.o. form day 2 to day 8 o.d. |
|
|
4 |
Test Drug (25 mg/kg) |
D-galactosamine (800mg/kg)
i.p on day 1 o.d + Test Drug form day 2 to day 8 o.d. |
Doxorubicin
induced hepatotoxicity in mice.
Mechanism
of action:
The
animals treated with doxorubicin resulted in a significant hepatic damage. (17)
Doxorubicin drastically decreases the levels of Cytochrome P-450 in liver.
Deficiency in these drug metabolizing reactions often results in slower
clearance and potentially deleterious side effects and toxicities related to
accumulation in the body. So the decrease in xenobiotic metabolizing proteins
could have resulted into slow clearance of doxorubicin and exacerbation on
normal cells.
Doxorubicin
can stimulate NADPH dependent microsomal lipid peroxidation apparently by
generating reactive species Superoxide ions, hydroxyl radical and
electronically excited singlet oxygenic believed to initiate and propagate
peroxidation of unsaturated membrane lipids. The reduced oxygen species,
particular OH- (hydroxyl) radical interacts with lipids, proteins and nucleic
acids resulting in loss of membrane integrity, structural or functional changes
in proteins and genetic mutation Carbon tetrachloride induced hepatotoxicity in
rats. (18)
Table No.5. Experimental
Protocol (Grouping, Treatment and Observations)
|
Sr.No |
Group (N=6) |
Treatment and Dose\day. |
Observations |
|
I.
|
Normal control |
Control (distilled water
p.o |
1)Biochemical parameter on 11th
day. 2) Histopathological examination
on 11th day. |
|
II.
|
Negative control |
Doxorubicin (2mg/kg) i.p on day 1,3,5,7 o.d. |
|
|
III.
|
Positive control |
Doxorubicin (2mg/kg) i.p on day
1,3,5,7 o.d. +Silymarin (100mg/kg) p.o
from day2 till day 10 o.d |
|
|
IV.
|
Test Drug (25 mg/kg) |
Doxorubicin (2mg/kg) i.p on day
1,3,5,7 o.d. +
Test Drugp.o. form day 2 to day 8 o.d |
Ethynyl estradiol induced
cholestasis in rats
Mechanism of action:
The
formation of bile is a vital function, and its impairment by drugs or
infectious, autoimmune, metabolic, or genetic disorders results in the syndrome
commonly known as cholestasis. (19) The secretion of bile normally
depends on the function of a number of membrane transport systems in
hepatocytes and bile-duct epithelial cells (cholangiocytes) and on the
structural and functional integrity of the bile-secretory apparatus. This
review summarizes the molecular defects in hepatocellular membrane transporters
that are associated with various forms of cholestasis liver disease
inhumans.Several animal models of intrahepatic and obstructive cholestasis
simulate human cholestasis diseases. These disorders include sepsis-induced
cholestasis (in endotoxin-treated rats), oral-contraceptive –induced
cholestasis and cholestasis of pregnancy (in ethyl estradiol–treated rats), and
extra hepatic biliary obstruction induced by ligation of the common bile duct.
The cholestatic effects of endotoxin and endotoxin-induced cytokines not only
have a role in the pathogenesis of sepsis-induced cholestasis, but also may
explain defects inhepatobiliary excretory function during total parenteral nutrition
and in alcoholic and viral hepatitis.(20)Many drugs (e.g., cyclosporine A and chlorpromazine)
also cause intrahepatic cholestasis at the level of the bilecanaliculus in both
humans and animals despite their different causes, each of these diseases results
in marked functional impairment of hepatocellular uptake and canalicular
excretion of bile salts and various other organic anions. (21) Cholestasis results from
impaired transport of these compounds into bile and the loss of osmotic driving
forces for bile secretion.
Table No.6. Experimental
Protocol (Grouping, Treatment and Observations)
|
Sr.No |
Group (N=6) |
Treatment and Dose\day. |
Observations |
|
I.
|
Normal control |
Control (distilled water
p.o) |
1) Biochemical parameter on
14th day. 2) Function parameter on 14th
day. 3) Histopathological
examination on 14th day. |
|
II.
|
Negative control |
Ethynyl estradiol 5mg/kg)
from day 1 to day 5 o.d. |
|
|
III.
|
Positive control |
Ethynyl estradiol 5mg/kg)
from day 1 to day 5 o.d. Picroliv (12mg/kg) p.o. form day 6 till day 13 o.d. |
|
|
IV.
|
Test Drug (25 mg/kg) |
Ethynyl estradiol 5mg/kg)
from day 1 to day 5 o.d+ Test Drugp.o. form
day 6 till day 13 o.d. |
SUMMARY AND CONCLUSION:
Summary:
The
present study demonstrated that Test drug showed significant activity in all
the model of hepatotoxicity employed for the study. The activity of Test drugs
when compared with standard like Silymarin, Livfit and Picroliv showed similar
or increased hepatoprotective and regenerative activity. In models which cause
hepatotoxicity by generation of free radicals like incase of carbon
tetrachloride toxicity which causes the loss of cell membrane integrity or in
case of the heavy metal toxicity like iron overload which generates free
radicals which causes the lipid peroxidation of the cell membrane, the Test
drugs showed better results than that of Silymarin.
In
the model which causes the hepatotoxicity by fatty accumulation like incase of
the alcohol, the herbal mixture showed better results than that of Silymarin.
In
drug induced hepatotoxicity like in case of paracetamol and doxorubicin whose
toxic metabolite causes the lipid peroxidation, the Test drugs showed similar effects to that of Silymarin.
While in case drugs that causes cholestasis by impaired membrane transport
system of bile like in case of ethynyl estradiol, the effects shown by Test
drugs were better as compared to that of Picroliv. In viral hepatitis
resembling model i.e. in case of D-galactosamine induced hepatotoxicity which
cause the reduction in the ATP and glycogen synthesis
CONCLUSION:
Taking
in to consideration the results obtained in the present investigation, it can be
concluded that Test Drug has a definite hepatoprotective and regenerative
activity; hence it could be used in the treatment of liver disorders like liver
dysfunction, hepatomegaly, viral hepatitis and various alcoholic live
disorders.
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Received on 07.09.2015 Modified on 25.09.2015
Accepted on 28.09.2015 © RJPT All right reserved
Research J. Pharm. and Tech. 8(12): Dec., 2015; Page 1725-1732
DOI: 10.5958/0974-360X.2015.00310.8