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Effect of curcumin and its analogue on lipids in carbon tetrachloride-induced hepatotoxicity: A comparative study

Effect of curcumin and its analogue on lipids in carbon tetrachloride-induced hepatotoxicity: A comparative study

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Published by rrukkumani
26. Kamalakkannan, N., Rukkumani, R., Viswanathan, P., Rajasekharan, K.N. and Menon, V.P. (2005) Effect of curcumin and its analogue on lipids in carbon tetrachloride-induced hepatotoxicity: A comparative study. Pharmaceut. Biol. 43, 460-466
26. Kamalakkannan, N., Rukkumani, R., Viswanathan, P., Rajasekharan, K.N. and Menon, V.P. (2005) Effect of curcumin and its analogue on lipids in carbon tetrachloride-induced hepatotoxicity: A comparative study. Pharmaceut. Biol. 43, 460-466

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Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Pharmaceutical Biology
Publication details, including instructions for authors and subscription information:http://www.informaworld.com/smpp/title~content=t713721640
Effect of Curcumin and its Analogue on Lipids in Carbon Tetrachloride-Induced Hepatotoxicity: A Comparative Study
N. Kamalakkannan
a
; R. Rukkumani
a
; P. Viswanathan
b
; K. N. Rajasekharan
c
; Venugopal P. Menon
aa
Department of Biochemistry, Faculty of Science,
b
Department of Pathology, Faculty of Medicine,Rajah Muthiah Medical College, Annamalai University, Annamalainagar, Tamil Nadu, India
c
Department of Chemistry, Faculty of Science, Kerala University, Kariavattom, Kerala, India
To cite this Article
Kamalakkannan, N., Rukkumani, R., Viswanathan, P., Rajasekharan, K. N. and Menon, VenugopalP.(2005) 'Effect of Curcumin and its Analogue on Lipids in Carbon Tetrachloride-Induced Hepatotoxicity: AComparative Study', Pharmaceutical Biology, 43: 5, 460 — 466
To link to this Article: DOI:
10.1080/13880200590963880
URL:
Full terms and conditions of use:http://www.informaworld.com/terms-and-conditions-of-access.pdfThis article may be used for research, teaching and private study purposes. Any substantial orsystematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply ordistribution in any form to anyone is expressly forbidden.The publisher does not give any warranty express or implied or make any representation that the contentswill be complete or accurate or up to date. The accuracy of any instructions, formulae and drug dosesshould be independently verified with primary sources. The publisher shall not be liable for any loss,actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directlyor indirectly in connection with or arising out of the use of this material.
 
Effect of Curcumin and its Analogue on Lipids in CarbonTetrachloride–Induced Hepatotoxicity: A Comparative Study
N. Kamalakkannan
1
, R. Rukkumani
1
, P. Viswanathan
2
, K.N. Rajasekharan
3
, and Venugopal P. Menon
11
Department of Biochemistry, Faculty of Science, and
2
Department of Pathology, Faculty of Medicine, Rajah MuthiahMedical College, Annamalai University, Annamalainagar, Tamil Nadu, India;
3
Department of Chemistry, Faculty of Science, Kerala University, Kariavattom, Kerala, India
Abstract
Curcumin and its analogue (
bis
demethoxy curcuminanalogue [BDMC-A]) were studied for their possiblelipid-lowering properties in carbon tetrachloride (CCl
4
)-induced hepatotoxicity in rats. Carbon tetrachloride(3mlkg
À
1
wk
À
1
) administration to albino Wistar ratsincreased the levels of hepatic marker enzymes such asaspartate transaminase (AST), alkaline phosphatase(ALP), and
c
-glutamyl transferase (GGT) in the plasma.The levels of lipids cholesterol, triglycerides, and freefatty acids were also increased in plasma and tissues(liver, kidney, heart, and brain). Phospholipid levelsincreased in plasma, heart, and brain but decreased inliver and kidney. Curcumin (80mg
=
kg) and BDMC-A(80mg
=
kg) administration to CCl
4
-treated rats for a per-iod of 3 months significantly decreased the lipid levels.The effect exerted by BDMC-A was more prominentthan that of curcumin. Studies on the histopathologyof the liver are also in line with the biochemicalparameters studied. These observations show the lipid-lowering efficacy of curcumin and its analogue in CCl
4
-induced hepatotoxicity.
Keywords:
bis
demethoxy curcumin analogue, carbontetrachloride, curcumin, lipids.
Introduction
Carbon tetrachloride (CCl
4
) is an important model agentto study the pathogenesis of liver injury (Boll et al.,2001). It is known to cause damage to the liver, lungs,adrenals, and central nervous system in humans andexperimental animals (McGregor & Lang, 1996). CCl
4
requires biotransformation by hepatic microsomal P450to produce the hepatotoxic metabolite, trichloromethylradical (CCl
3
) which, in the presence of oxygen, is furtherconverted to a peroxy radical (CCl
3
OO
). These radicalsmay interact with membrane lipids leading to peroxi-dation (Muriel, 1997). CCl
4
causes an imbalance betweenthe synthesis and degradation of lipids (Boll et al., 2001).
Curcuma longa
Linn. (Zingiberaceae) is a medicinalplant widely cultivated in tropical regions of Asia. Cur-cumin (diferuloyl methane) (Figure 1) is extracted fromthe rhizomes of 
Curcuma longa
. Curcumin possesses awide variety of pharmacological properties (Quiles et al.,2002). The lipid-lowering effect of curcumin in CCl
4
-induced hepatotoxicity (Akila et al., 1998) and in alcoholand polyunsaturated fatty acid–induced hyperlipidemia(Rukkumani et al., 2002) were reported.
bis
demethoxy-curcumin (BDMC) is a natural curcuminoid that alsopossess lipid-lowering properties in high fat diet–inducedlipid accumulation (Asai & Miyazawa, 2001). An ana-logue of 
bis
demethoxycurcumin (BDMC-A) (Figure 2)has been reported for its hypolipidemic properties(Rukkumani et al., 2004a) along with its antioxidant(Rukkumani et al., 2004b) and antidiabetic (Anusuyaet al., 2003) properties.
Accepted: April 1, 2005
Address correspondence to
: Dr. Venugopal P. Menon, Professor and Head, Department of Biochemistry, Annamalai University,Annamalainagar 608 002, Tamil Nadu, India. Tel:
þ
91 4144 238343; Fax:
þ
91 4144 238343; E-mail: biocmr@sify.com
Figure 1.
Curcumin.DOI: 10.1080/13880200590963880
#
2005 Taylor & Francis Ltd.Pharmaceutical Biology2005, Vol. 43, No. 5, pp. 460–466
 D o w nl o ad ed  B y : [ N o v a r ti s  si t e li c e n s e]  A t : 11 :04 9  M a r ch 2010
 
There are no available reports on the hypolipidemicproperties of BDMC-A in CCl
4
-induced hepatotoxicity.Hence, we made an attempt to study the effect of BDMC-A and to compare it with curcumin on lipid pro-file in CCl
4
-induced hepatotoxicity in rats.
Materials and Methods
Drugs and chemicals
Curcumin was obtained from Sigma Chemical Company(St. Louis, MO, USA). BDMC-A was synthesised asdescribed by Babu and Rajasekharan (1994). CCl
4
waspurchased from Merck Ltd. (Mumbai, India). All otherchemicals and biochemicals used in our study were of high analytical grade.
Experimental animals
Male albino Wistar rats of body weight 150–180g wereobtained from the Central Animal House, RajahMuthiah Medical College and Hospital, AnnamalaiUniversity. The rats were housed in polypropylene cageslined with husk. They were fed on a standard pellet diet(Agro Corporation Private Ltd., Bangalore, India), andwater was freely available. The standard pellet diet com-prised 21
%
protein, 5
%
lipids, 4
%
crude fiber, 8
%
ash,1
%
calcium, 0.6
%
phosphorus, 3.4
%
glucose, 2
%
vitamin, and 55
%
nitrogen-free extract (carbohydrates).
It provides metabolizable energy of 3600kcal 
=
kg
.
Experimental design
A total of 36 rats were used in our study. The rats weredivided into 6 groups of 6 rats each.Group I Normal control rats injected with saline subcu-taneously (3ml
=
kg body weight per week) and orallyadministered with saline.Group II Normal rats injected with saline subcu-taneously (3ml
=
kg body weight per week) and orallyadministered curcumin (80mg
=
kg body weight)(Rukkumani et al., 2002).Group III Normal rats injected with saline subcuta-neously (3ml
=
kg body weight per week) and orallyadministered BDMC-A (80mg
=
kg body weight)(Anusuya et al., 2003).Group IV Rats subcutaneously injected with CCl
4
(3ml
=
kg body weight per week) (Akila et al., 1998)and orally administered saline.Group V Rats orally administered curcumin (80mg
=
kgbody weight) along with subcutaneous injection of CCl
4
(3ml
=
kg body weight per week).
Figure 2.
BDMC-A.
Figure 3.
Liver section of normal rat showing normalparenchymal architecture (H&E,
Â
10).
Figure 4.
No histological alterations were observed in ratstreated with curcumin or BDMC-A (H&E,
Â
10).
Figure 5.
No histological alterations were observed in ratstreated with curcumin or BDMC-A (H&E,
Â
10).
Curcumin and its analogue on lipids 461
 D o w nl o ad ed  B y : [ N o v a r ti s  si t e li c e n s e]  A t : 11 :04 9  M a r ch 2010

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