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Research Article
HEPATPORTECTIVE ACTIVITY OF ELETTARIA CARDAMOMUM AGAINST PARACETAMOL INDUCED HEPATOTOXICITY
NIMMY CHACKO*, AMBILY THOMAS, C S SHASTRY, PRERANA SHETTY
*Department of Pharmacology, NGSM Institute of Pharmaceutical Sciences, Paneer, Deralakatte, Manglore, Karnataka, India. Email: [email protected]
Received: 15 Mar 2012, Revised and Accepted: 21 Apr 2012
ABSTRACT
Aim of study: To evaluate the hepatoprotective activity of fruits of Elettaria cardamomum extract against Paracetamol induced hepatotoxicity.
Materials and methods: Methanolic extract at doses of 100, 200 and 400 mg/kg were administered orally once daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin, along with histopathological studies of liver.
Result: Elettaria cardamomum exhibited significant hepatoprotective activity by reversing bio‐chemical changes induced by paracetamol. Histology of the liver sections of the animals treated with the extracts showed the presence of almost normal hepatocytes, absence of necrosis and fatty infiltration, which further evidenced the hepatoprotective activity.
Conclusion: Methanolic extract of fruits of Elettaria cardamomum has liver protective effect against paracetamol induced hepatotoxicity. Further studies are needed to isolate and characterize the active principles and to find out the mechanism responsible for its hepatoprotective activity.
Keywords: Antihepatotoxic, Paracetamol, Elettaria cardamomum, Liver injury.
INTRODUCTION
Liver is one of the largest organs in human body and the chief site for intense metabolism and excretion. So it has a surprising role in the maintenance, performance and regulating homeostasis of the body 1. The major functions of the liver are carbohydrate, protein and fat metabolism, detoxification, secretion of bile and storage of vitamins. Thus, to maintain a healthy liver is a crucial factor for overall health and well being. But it is continuously and variedly exposed to environmental toxins, prescribed and over‐the‐counter drugs which can eventually lead to various liver ailments like hepatitis, cirrhosis and alcoholic liver disease 2. Thus liver diseases are some of the fatal disease in the world today. They pose a serious challenge to international public health. Modern medicines have little to offer for alleviation of hepatic diseases and it is chiefly the plant based preparations which are employed for the treatment of liver disorders. But there is not much drug available for the treatment of liver disorders 3. In absence of a reliable liver protective drug in the modern system of medicine, a number of medicinal preparations in Ayurveda, the Indian system of medicine, are recommended for the treatment of liver disorders. Natural remedies from medicinal plants are considered to be effective and safe alternative treatments for hepatotoxicity 4. In view of this, the present study is undertaken to investigate the hepatoprotective activity of Elettaria cardamomum fruits against paracetamol induced hepatotoxicity in rats.
MATERIALS AND METHODS
Plant material and extraction
The dried fruits of Elettaria cardamomum were purchased from the local markets of Kerala in the month of June 2010. The fruits were identified and authenticated by Dr. Jomy Augustine, Head of the Department of Botany, St. Thomas College, Pala, Kerala. After cleaning of adulterant material, the fruits were ground with an electric grinder into a coarse powder. About 500 g of ground material was soaked in methanol (70%) at room temperature (23–25 C) for 3 days with occasional shaking. It was filtered through a muslin cloth and then through a Whatman qualitative grade 1 filter paper. This procedure
was repeated twice and the combined filtrates were evaporated on rotary evaporator under reduced pressure (−760 mmHg) to a thick, semi‐solid pasty mass of dark brown color; i.e. the crude extract yielding approximately 4.9%.
Experimental animals
Albino Wistar rats of either sex (150‐200 g) were obtained from the laboratory of NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangalore. Four animals were housed in a cage in a climate‐controlled room under standard conditions with 12:12 hour’s light/dark cycles and free access to water and food. Animals were brought in to the laboratory for at least a week before experimental testing commenced. Each experimental group of rats were randomly chosen and used only once. All the experiments were performed within the guidelines of the institutional animal ethical committee of KSHEMA. Deralakatte, Mangalore (KSHEMA/AEC/40/2010).
Hepatoprotective Activity
Animals were divided into six groups of 6 animals each. The first group received saline 1 ml/kg for one week (control). The group II received saline 1 ml/kg for one week (positive control). The group III received silymarin (25 mg/kg p.o.). The group IV, V and VI received 100, 200 and 400 mg/kg of extract respectively once a day for seven days. On the fifth day, after the administration of the respective treatments, all the animals of groups II, III, IV, V and VI were administered with paracetamol 2 g/kg orally. On the seventh day after 2 h of respective treatments, the blood samples were collected from all groups of rats by puncturing the retro‐orbital plexus. Serum was separated by centrifugation at 2500 rpm at 37oC for 15 min and analyzed for various biochemical parameters. Liver was dissected out and used for histopathological studies 5.
Assessment of liver functions
Biochemical parameters, such as Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Total bilirubin (TBIL) were estimated using the assay kit (AGAPPE Diagnostics Ltd, Ernakulam, Kerala).
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491 Vol 4, Issue 3, 2012
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Groups (n=6) Control Pcml Treated Pcml + Silymari(25 mg/kg bodyPcml + MEC (100 mg/kg bodPcml + MEC (200 mg/kg bodPcml + MEC (400 mg/kg bod
sed as mean ± SE
0.05) compared t
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Fig. 3: Liver t
out and fixed (50–100%) cleamm thick sectiomatoxylin and
an ± S.E.M. Statiswere analyzed bycomparison tes
thanolic extract
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tissue: Silymarin
in 10% formaared in xylene aons were prepar
eosin dye
stical differencesy one‐way ANOst using SPSS 1
ts of fruits of Ele
ALT (IU/L) 89.0±1.15 288.3±1.47a 97.83±1.66b
195.2±1.13
134.5±1.12b
112.8±2.97b
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AST (IU/L110.2±1.3383.8±3.3123.8±2.7
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SULTS
e methanolic extrnontoxic when aund to be safe up t
rum parameters
ministration of pevidenced by
etreatment of ratshibited markedpatotoxicity, (shotract of Elettaria cthe standard, sily
mum on paracet
L) ALP (5 142.08a 389.71b 152.3
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5b 169.0
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ract of fruits of Eladministered orato 2 g/kg body w
s determination
aracetamol to rathe altered s
s with methanolid protection own in Table 1). Tcardamomum weymarin.
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Pharm Sci, Vol 4,
lettaria cardamomally to rats and itt.
ts caused significserum biochemc extract of Elettaagainst parac
The effects producere comparable w
epatotoxicity in
otal Bilirubin (m.74±0.02 .23±0.02a .85±0.02b
.74±0.01
.15±0.01b
.88±0.01b
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tract) Group Tre
, Issue 3, 611613
61
mum was found tts LD50 value wa
cant liver damagemical parametersaria cardamomumetamol induceced by methanoliwith that produce
rats.
mg/dL)
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DISCUSSION AND
The present studyactivity of methanmethanolic extracmortality up to 20
Administration ofALP and Total Bila toxic electrophimethanolic extraprevent the elevparacetamol. Theeffects on cytochr,7. These biochhistopathological
Paracetamol is noOnly 5% of tbenzoquineimine.paracetamol, theaturated and henoxidized to highlcytochrome‐450 electron reductionof cellular membrhe tissue damage
With aid of enzymcan conclude that have hepatoprotdamage. Further active principles hepatoprotective
Liver tissue: (20
D CONCLUSION
y was under takenolic extract of fct did not show an000 mg/kg dose.
f paracetamol eleirubin significantile, N‐acetyl‐p‐bect of fruits of Evation of ALT, se biochemical erome P450 and/hemical findingsstudies.
ormally eliminatethe paracetamo. However, upone sulfation andnce, higher percely reactive N‐aceenzymes. A semn of NAPQI, can rane and increasee 8.
me levels and histmethanolic extraective activity studies are needand to find out activity.
00mg/kg extract
n to determine thfruits of Elettariany sign and symp
evated the serumtly. This is due toenzoquine‐imine.Elettaria cardamoAST, ALP and effects may be duor promotion of s were further
ed mainly as sulfal is convertedn administrationd glucuronidatioentage of paracetetyl‐p‐benzoquinmiquinone radicacovalently binds es the lipid perox
topathological stuact of fruits of Eleagainst Paracetaded to isolate anthe mechanism
t) Treated Group
he hepatoprotecta cardamomum. Tptoms of toxicity a
m levels of ALT, Ao its bioactivation Pretreatment womum was able Total Bilirubin ue to the inhibitoits glucuronidatsubstantiated
ate and glucuronid into N‐acetyln of toxic doses on routes becotamol molecules eimine (NAPQI) al, obtained by oto macromolecuxidation resulting
udies of rat liver ettaria cardamomamol induced livnd characterize responsible for
Chacko et al.
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ide. l‐p‐of
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Fig. 6: Liver tissu
KNOWLEDGEME
e author is thanarmaceutical Scies study.
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