Pharmacological Research, Vol. 46, No.

3, 2002
doi:10.1016/S1043-6618(02)00149-4, available online at http://www.idealibrary.com on

COMPARATIVE EFFECTS OF CURCUMIN AND PHOTO-IRRADIATED

CURCUMIN ON ALCOHOL- AND POLYUNSATURATED
FATTY ACID-INDUCED HYPERLIPIDEMIA
R. RUKKUMANI a , M. SRI BALASUBASHINI a , P. VISHWANATHAN b and V.P. MENON a,∗
a Departmentof Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar 608 002,
Tamil Nadu, India, b Department of Pathology, Faculty of Medicine, Raja Muthiah Medical College,
Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India

Accepted 1 July 2002

It is a known fact that ethanol increases lipid levels in humans and experimental animals. Reports show
that the increased intake of polyunsaturated fatty acids (PUFAs) along with alcohol produces various
pathological changes in liver resulting in hyperlipidemia. Heating of oil rich in PUFA produces
various lipid peroxidative end products, which aggravate the pathological changes. In the present
study, we have investigated the effect of curcumin (C) and photo-irradiated curcumin (IC) on alcohol-
and PUFA-induced hyperlipidemia. Our results showed that the activities of alkaline phosphatase
(ALP), γ -glutamyl transferase (GGT) in plasma and levels of cholesterol, triglycerides (TGs) and
free fatty acids (FFAs) in tissues were increased significantly in both alcohol + raw as well as heated
PUFA groups compared to normal, but decreased significantly on treatment with curcumin and IC.
The IC treatment decreased the levels more significantly compared to curcumin. The phospholipids
(PLs) were increased significantly in heart and intestine and decreased in liver and kidney in both
alcohol + raw as well as heated PUFA groups. The levels were significantly decreased in liver and
kidney and increased in intestine and heart in both curcumin- and IC-treated groups. But the effect
of IC was more pronounced than curcumin. Histopathological observations were also in correlation
with the biochemical parameters. Thus, photo-irradiated curcumin proves itself to be more effective
than curcumin in treating the above pathological conditions.
© 2002 Elsevier Science Ltd. All rights reserved.

Key wo rds: alcohol, PUFA, curcumin, photo-irradiated curcumin, lipids.

INTRODUCTION role of polyunsaturated fatty acids (PUFAs) is gaining

Alcohol, a toxic substance in excess causes various
biochemical, pharmacogenetic and pathological distur-
bances. Ethanol produces fatty liver with ultrastructural
lesions both in rats and human. It occurs when the in-
tracellular redox potential and redox sensitive nutrient
metabolisms are disturbed by alcohol [1]. An excessive
accumulation of reducing equivalents favours hepatic
lipogenesis, decreases hepatic release of lipoproteins, in-
creases the mobilisation of peripheral fat, enhances the
uptake of circulating lipids and decreases the fatty acid
oxidation, and thus increases the retention of lipids in liver.
The composition of macronutrient is a determinant
of nutritional health. Fat is an important dietary com-
ponent, which affects both growth and health. Dietary
∗ Corresponding author. Department of Biochemistry, Faculty of Science,
Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.
E-mail: cmrana@md3.vsnl.net.in
a greater attention now a day in the research world. In
contrast to earlier epidemiological studies showing the
reduced risk of coronary heart disease (CHD) due to
PUFA intake [2], current data on dietary fats indicate
that it is not just the presence of PUFA but the type of
PUFA that is important. A high PUFA n-6 content and
n-6/n-3 ratio in dietary fats is considered to be athero-
genic and diabetogenic. The newer heart friendly oils
like sunflower oil possess this undesirable PUFA content
and thus the excess intake of these vegetable oils are
actually detrimental to health [3]. Moreover, heating of
oil produces various peroxidative changes. During deep
fat frying, when the fat is used repeatedly, oxidative and
thermal effects result in the formation of many volatile
and non-volatile products, some of which are toxic de-
pending on the level of intake [4]. Ingestion of decompo-
sition products formed as a result of thermal abuse and
oxidation of frying oils is known to lead to a variety of
diseases [5]. Thus, the ingestion of alcohol along with

1043-6618/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
258 Pharmacological Research, Vol. 46, No. 3, 2002

PUFA and heated PUFA is expected to alter the lipid
levels. In our present study, we have investigated the influ-
ences of curcumin (bis-4-hydroxy-3-methoxy-phenyl)-1,
6-hepta-diene-3,5-dione, an active principle of Curcuma
longa and photo-irradiated curcumin on alcohol- and
PUFA-induced hyperlipidemia, since little or no work has
been done on treating these conditions and compared their
effects. Curcumin on UV irradiation produces vanillin
and ferulic acid, the stable photoproducts [6], and no data
are available regarding its hypolipidemic effects.

Fig. 1. (A) Control animals liver: H&E, ×20. Hepatocytes arranged in a linear pattern without dilatation of the sinusoids and portal triad ( ).
(B) Alcohol + raw PUFA fed rats liver: H&E, ×20. Sinusoidal dilatation ( ), congestion ( ), fatty changes especially microvesicular type
( ). (C) Alcohol + raw PUFA + curcumin fed rats liver: H&E, ×20. Fatty changes of hepatocyte especially microvesicular (→) and dilatation ( )
of the sinusoids; ( ) indicates portal vein. (D) Alcohol + heated PUFA fed rats liver: H&E, ×20. Focal fatty changes of parenchyma, predominantly
macro-vesicular ( ). (E) Alcohol+heated PUFA+curcumin fed rats liver: H&E, ×20. Fatty changes of hepatocytes especially microvesicular ( )
and dilatation of the sinusoids ( ). (F) Alcohol + heated PUFA + irradiated curcumin fed rats liver: H&E, ×20. Fatty changes of macrovesicular type
( ). (G) Control rats kidney: H&E, ×20. Normal glomeruli ( ) and tubules. (H) Alcohol +raw PUFA fed rats kidney: H&E, ×20. Cloudy swelling
of tubule ( ) and congested blood vessels ( ). (I) Alcohol + raw PUFA + curcumin fed rats kidney: H&E, ×20. Area of haemorrhage ( ). (J)
Alcohol+heated PUFA fed rats kidney: H&E, ×20. Fatty infiltrate ( ). (K) Alcohol+heated PUFA+curcumin fed rats kidney: H&E, ×20. Multiple
areas of haemorrhage ( ). (L) Alcohol + heated PUFA + irradiated curcumin fed rats kidney: H&E, ×20. Multiple areas of haemorrhage ( ).
Pharmacological Research, Vol. 46, No. 3, 2002 259

Fig. 1. (Continued ).

MATERIALS AND METHODS Animals and treatment

Group 1: Control rats (rats given standard pellet
Female Albino rats, Wistar strain of body weight rang- diet and glucose solution isocalorific to
ing 140–150 g bred in the central Animal House, Rajah ethanol and a high fat diet, orally using
Muthiah Medical College, Chidambaram, were fed on an intragastric tube).
pellet diet (Agro Corporation Private Limited, Banga- Group 2: Rats given 20% ethanol [7] orally
lore, India) and water, ad libitum. The standard pellet using an intragastric tube and a high
diet comprised 21% protein, 5% lipids, 4% crude fi- fat diet (15%) (raw sunflower oil
bre, 8% ash, 1% calcium, 0.6% phosphorus, 3.4% glu- mixed with the diet).
cose, 2% vitamins and 55% carbohydrates and provides Group 3: Rats given 20% ethanol and a high fat
metabolisable energy of 3600 kcal kg−1 . The animals diet (15%) (thermally oxidised
were housed in plastic cages under controlled condi- sunflower oil).
tions of 12-h light/12-h dark cycle, 50% humidity and Group 4: Rats given curcumin (80 mg kg−1
at 30 ± 3 ◦ C. body weight) [8], dissolved in 20%
ethanol (7.99 g kg−1 body weight)
orally using an intragastric tube and a
Materials used high fat diet (15%) (raw sunflower oil).
Sunflower oil: Sunflower oil marketed by Gold
Winner was purchased from Group 5: Rats given curcumin (80 mg kg−1
local market, Chidambaram, body weight) dissolved in 20% ethanol
Tamil Nadu, India. (7.9 g kg−1 body weight) and a high fat
Curcumin (C): Curcumin was obtained from diet (15%) (heated sunflower oil).
central drug house private Group 6: Rats given photo-irradiated curcumin
limited, Mumbai, India. (80 mg kg−1 body weight) dissolved in
Heated PUFA: Sunflower oil was subjected to 20% ethanol (7.9 g kg−1 body weight)
heating at 180 ◦ C for 30 min, and a high fat diet (15%) (heated
twice. sunflower oil) (Table I).
Irradiated Curcumin was subjected to
curcumin (IC): photo-oxidation by curcumin At the end of experimental period (45 days), the rats
exposing curcumin to bright were sacrificed after an overnight fast by decapitation.
sunlight for 5 h continuously. Tissues (liver, heart, kidney and intestine) were removed,
All other chemicals and solvents used were of analytical cleared off blood and immediately transferred to ice-cold
grade. containers containing 0.9% NaCl for various estimations.
260 Pharmacological Research, Vol. 46, No. 3, 2002

Table I
Experimental design

Group No. of rats Treatment Dose administered

Normal (N) 8 Glucose 36.2 g kg−1 body weight (b.w.)

Alcohol + raw PUFA (A + R)
Alcohol + heated PUFA (A + H)
Alcohol + raw PUFA + curcumin
(A + R + C)
Alcohol + heated PUFA +
curcumin (A + H + C)
Alcohol + heated PUFA + photo-
irradiated curcumin (A + H + IC)
8 20% alcohol + high fat diet
8 20% alcohol + high fat diet
8 20% alcohol + high fat diet + curcumin
8 20% alcohol + high fat diet + curcumin
8 20% alcohol + high fat diet
+ irradiated curcumin
7.9 g kg−1 b.w. ethanol + 15% fat
(raw sunflower oil)
7.9 g kg−1 b.w. ethanol + 15% fat
(heated sunflower oil)
7.9 g kg−1 b.w. ethanol + 15% fat
(raw sunflower oil) + 80 mg kg−1
b.w. curcumin
7.9 g kg−1 b.w. ethanol + 15% fat
(heated sunflower oil)
+ 80 mg kg−1 b.w. curcumin
7.9 g kg−1 b.w. ethanol + 15% fat
(heated sunflower oil) + 80 mg kg−1
b.w. irradiated curcumin

Average food intake per day: Ω 15 g/150 g rat. Total calories per day: 508 kcal/150 g rat.

For histopathological study, two animals from each group Table II

were perfused with formalin (10%) and the tissues were Levels of marker enzymes in plasma (values are mean ± SD from
six rats in each group)
separated and stored in 10% formalin. They were later
sectioned using a microtome, dehydrated in graded alco- Groups GGT (IU l−1 ) ALP (IU l−1 )
hol, embedded in paraffin section and stained with haemo- 1. N 0.597 ± 0.06 85.880 ± 7.00
toxylin and eosin (H&E). 2. A + R 1.658 ± 0.16a 174.020 ± 15.85a
3. A + H 2.508 ± 0.14a 239.560 ± 22.14a
4. A + R + C 0.783 ± 0.13b,c 119.780 ± 10.21a,c
Biochemical estimations 5. A + H + C 1.433 ± 0.12a,d 177.410 ± 16.28a,d
The activities of alkaline phosphatase (ALP) (EC 6. A + H + IC 1.150 ± 0.16a,d,e 149.147 ± 12.13a,d,f
3.1.3.1) were assayed by PNPP method [9], using a reagent F-ratio 160.764 77.259
kit, and γ -glutamyl transferase (GGT) (EC 2.3.2.2) by
ANOVA followed by LSD. Groups 2–6 are compared with group 1;
fixed time method of Fiala et al. [10]. The tissue lipids group 4 is compared with group 2; groups 5 and 6 are compared with
were extracted according to the method of Folch et al. group 3; group 6 is compared with group 5. a P ≤ 0.001. b P ≤ 0.01.
[11], cholesterol was estimated by Zlatkis et al. method c P ≤ 0.001. d P ≤ 0.001. e P ≤ 0.001. f P ≤ 0.01.

[12], phospholipids (PLs) by the method of Zilversmit

and Davis [13], free fatty acids (FFAs) by Falholt et al.
method [14] and triglycerides (TGs) by Foster and Dunn
[15] method.
Statistical analysis
The data given in the tables are average values±standard
deviation (SD). Data were analysed statistically by anal-
ysis of variance (ANOVA) and groups were compared by
least significant difference (LSD).
RESULTS
Changes in the activities of plasma γ -glutamyl
transferase and alkaline phosphatase
Activities of GGT and ALP are given in Table II. The
activities of GGT and ALP were increased significantly
in alcohol + raw and thermally oxidised PUFA groups
compared to normal. Curcumin treatment significantly
decreased the activities of GGT and ALP compared to
above groups. Treatment of alcohol + thermally oxidised
PUFA with photo-irradiated curcumin showed a signifi-
cant decrease in the activities of GGT and ALP compared
to treatment with curcumin.
Changes in lipids
The levels of cholesterol (Table III), TG (Table IV) and
FFA (Table V) were increased significantly in alcohol +
raw as well as heated PUFA groups compared to normal.
But they were decreased significantly in curcumin-treated
group. The decrease was more significant in IC-treated
group compared to curcumin. The levels of PL (Table VI)
were increased in heart and intestine and decreased in
liver and kidney in alcohol + raw as well as heated PUFA
groups. But curcumin treatment decreased the PL levels in
heart and intestine and increased in liver and kidney. Sim-
ilar changes occurred in IC group but more significantly
than curcumin treatment.
Histopathological changes in liver
Histopathological changes of liver are given in Table
VII. The liver samples of alcohol + raw PUFA animals
showed sinusoidal dilatation, congestion and fatty changes
of microvesicular type and occasional macrovesicular
type fatty changes. On treatment with curcumin, the liver
showed dilatation and microvesicular fatty changes. The
alcohol + heated PUFA animal’s liver showed feathery
degeneration of hepatocyte and focal fatty infiltrate. On
Pharmacological Research, Vol. 46, No. 3, 2002 261

Table III
Levels of tissue cholesterol (values are mean ± SD from six rats in each group)

Groups Liver (mg/100 g tissue) Heart (mg/100 g tissue) Kidney (mg/100 g tissue) Intestine (mg/100 g tissue)

1. N 335.667 ± 26.36 182.167 ± 17.28 340.000 ± 59.38 174.000 ± 22.59

2. A + R 464.00 ± 32.42a 400.000 ± 26.89a 624.000 ± 39.30a 426.667 ± 30.22a
3. A + H 653.667 ± 34.33a 496.000 ± 26.86a 656.000 ± 48.03a 496.000 ± 44.13a
4. A + R + C 377.667 ± 31.68b ns 304.000 ± 26.89a,b 469.339 ± 39.81a,b 336.000 ± 30.37a,c
5. A + H + C 517.500 ± 28.28a,c 411.000 ± 18.36a,c 528.667 ± 26.18a,c 414.333 ± 30.31a,c
6. A + H + IC 452.667 ± 40.67a,c,d 373.333 ± 16.52a,c,d 464.500 ± 9.03a,c,d 370.00 ± 17.62a,c,e
F-ratio 80.454 134.784 50.139 86.630

ANOVA followed by LSD. Groups 2–6 are compared with group 1; group 4 is compared with group 2; groups 5 and 6 are compared with group 3;
group 6 is compared with group 5; ns: no significance. a P ≤ 0.001. b P ≤ 0.001. c P ≤ 0.001. d P ≤ 0.01. e P ≤ 0.05.

Table IV
Levels of tissue triglycerides (values are mean ± SD from six rats in each group)

Groups Liver (mg/100 g tissue) Heart (mg/100 g tissue) Kidney (mg/100 g tissue) Intestine (mg/100 g tissue)

1. N 332.37 ± 15.89 341.12 ± 22.31 461.38 ± 29.96 371.75 ± 25.82

2. A + R 542.80 ± 35.85a 503.75 ± 54.65a 690.98 ± 34.98a 524.17 ± 16.67a
3. A + H 607.89 ± 37.15a 581.65 ± 55.09a 795.94 ± 70.59a 638.50 ± 34.4a
4. A + R + C 424.73 ± 25.34a,b 424.21 ± 33.55a,c 546.92 ± 25.25b,d 443.89 ± 37.27a,b
5. A + H + C 575.01 ± 29.55a,e 502.93 ± 25.19a,f 669.12 ± 42.97a,e 542.29 ± 39.29a,e
6. A + H + IC 467.13 ± 45.33a,e,g 450.64 ± 26.12a,e,g 591.42 ± 36.39a,e,h 493.39 ± 23.36a,e,h
F-ratio 49.348 27.096 45.862 52.87

ANOVA followed by LSD. Groups 2–6 are compared with group 1; group 4 is compared with group 2; groups 5 and 6 are compared with group 3;
group 6 is compared with group 5. a P ≤ 0.001. b P ≤ 0.001. c P ≤ 0.01. d P ≤ 0.01. e P ≤ 0.001. f P ≤ 0.01. g P ≤ 0.05. h P ≤ 0.01.

Table V
Levels of tissue free fatty acids (values are mean ± SD from six rats in each group)

Groups Liver (mg/100 g tissue) Heart (mg/100 g tissue) Kidney (mg/100 g tissue) Intestine (mg/100 g tissue)

1. N 645.20 ± 63.38 483.55 ± 37.45 386.84 ± 37.45 253.86 ± 39.73

2. A + R 980.43 ± 71.95a 770.68 ± 63.10a 746.42 ± 62.97a 387.00 ± 36.32a
3. A + H 1160.53 ± 98.57a 834.14 ± 85.50a 894.57 ± 85.60a 519.82 ± 54.36a
4. A + R + C 761.80 ± 67.90b,c 573.00 ± 11.78c,d 483.55 ± 45.31c,d 310.18 ± 34.08b,e
5. A + H + C 942.49 ± 87.28a,f 647.26 ± 10.45a,f 628.03 ± 31.61a,f 443.62 ± 45.08a,g
6. A + H + IC 760.34 ± 74.29b,f ,h 580.00 ± 14.14d,f ,i 562.09 ± 41.54a,f ,i 360.73 ± 32.65a,f ,j
F-ratio 34.56 47.65 69.10 31.68

ANOVA followed by LSD. Groups 2–6 are compared with group 1; group 4 is compared with group 2; groups 5 and 6 are compared with group 3;
group 6 is compared with group 5. a P ≤ 0.001. b P ≤ 0.05. c P ≤ 0.001. d P ≤ 0.01. e P ≤ 0.01. f P ≤ 0.001. g P ≤ 0.01. h P ≤ 0.001.
i P ≤ 0.05. j P ≤ 0.01.

Table VI
Levels of tissue phospholipids (values are mean ± SD from six rats in each group)

Groups Liver (mg/100 g tissue) Heart (mg/100 g tissue) Kidney (mg/100 g tissue) Intestine (mg/100 g tissue)

1. N 1708.00 ± 76.52 1051.66 ± 44.00 1500.00 ± 53.67 680.00 ± 48.94

2. A + R 1040.00 ± 61.97a 1400.00 ± 61.97a 920.00 ± 61.97a 1140.00 ± 65.73a
3. A + H 883.33 ± 46.33a 1620.00 ± 65.73a 800.00 ± 61.97a 1260.00 ± 29.44a
4. A + R + C 1390.00 ± 79.75a,b 1173.33 ± 41.31a,b 1326.66 ± 68.90a,c 883.33 ± 29.44a,b
5. A + H + C 1240.00 ± 61.97a,c 1346.66 ± 78.66a,c 1206.67 ± 77.63a,c 1060.00 ± 48.99a,c
6. A + H + IC 1356.66 ± 48.03a,c,d 1210.83 ± 17.44a,c,e 1298.33 ± 24.88a,c,f 965.00 ± 32.09a,c,d
F-ratio 123.325 78.809 114.968 97.655

ANOVA followed by LSD. Groups 2–6 are compared with group 1; group 4 is compared with group 2; groups 5 and 6 are compared with group 3;
group 6 is compared with group 5. a P ≤ 0.001. b P ≤ 0.001. c P ≤ 0.001. d P ≤ 0.01. e P ≤ 0.05. f P ≤ 0.001.
262 Pharmacological Research, Vol. 46, No. 3, 2002

Table VII
Histopathological changes in liver

Microscopic observations N A+R A+R+C A+H A+H+C A + H + IC

Nuclear disintegration A ++ + +++ ++ +

Sinusoidal congestion A ++ + +++ ++ +
Portal inflammation A ++ + +++ ++ +
Steatosis in zones 2 and 3 A ++ + +++ ++ +
Cytoplasmic vacuolation A ++ + +++ ++ +
Focal degeneration A ++ + +++ ++ +
Fatty changes A ++ + +++ ++ +
Micronecrosis A ++ + +++ ++ +
Feathery degeneration A ++ + +++ ++ +

A + R PUFA—alcohol + raw PUFA; A + R PUFA + C—alcohol + raw PUFA + curcumin; A + H PUFA—alcohol + heated PUFA; A + H
PUFA + C—alcohol + heated PUFA + curcumin; A + H PUFA + IC—alcohol + heated PUFA + irradiated curcumin. A: absent; +: 0–5 LPF; ++:
5–10 LPF; +++: >10 LPF.

Table VIII
Histopathological changes in kidney

Microscopic observations N A+R A+R+C A+H A+H+C A + H + IC

Fatty changes A ++ + +++ ++ +

Inflammation of parenchyma A ++ + +++ ++ +
Vessel congestion A ++ + +++ ++ +
Haemorrhage A ++ + +++ ++ +

A + R PUFA—alcohol + raw PUFA; A + R PUFA + C—alcohol + raw PUFA + curcumin; A + H PUFA—alcohol + heated PUFA; A + H
PUFA + C—alcohol + heated PUFA + curcumin; A + H PUFA + IC—alcohol + heated PUFA + irradiated curcumin. A: absent; +: 0–5 LPF; ++:
5–10 LPF; +++: >10 LPF.

treatment with curcumin, congestion, dilatation and mi-
crovesicular fatty changes were seen. Photo-irradiated
curcumin-treated animals showed only macrovesicular
type fatty changes (Fig. 1A–F).
Histopathological changes of kidney
Table VIII gives the histopathological changes of kid-
ney. The kidney samples of alcohol + raw PUFA-treated
animals showed fatty infiltration, cloudy swelling and
congested blood vessels. On treatment with curcumin,
the samples showed areas of focal haemorrhage. Hyaline
cast, cloudy swelling, fatty infiltrate and parenchymal
inflammation were seen in alcohol + heated PUFA group
animals. Treatment with curcumin showed multiple ar-
eas of haemorrhage, cloudy swelling and fatty infiltrate.
Treatment with photo-irradiated curcumin showed only
multiple areas of haemorrhage (Fig. 1G–L).
DISCUSSION
Marked alterations in lipid metabolism have been re-
ported in chronic ethanol feeding [16]. The main pathway
of alcohol degradation, alcohol dehydrogenase pathway
leads to increased NADH synthesis. This striking redox
change inhibits TCA cycle, fatty acid oxidation, lipopro-
tein export and increases fatty acid uptake [17] and thus
predisposing fatty liver.
Ethanol treatments to rats are known to cause centrilob-
ular necrosis in the liver leading to the accumulation of fat.
The fats from peripheral adipose tissues are translocated
to liver, brain and kidney for accumulation. Antonenkov
et al. [18] have reported that chronic ethanol ingestion re-
sults in moderate hypercholesterolemia and hypertriglyc-
eridemia and increased concentration of lipids in liver.
The increased cholesterol may be due to increased
β-hydroxy-methyl-glutaryl CoA (HMG CoA) reductase
activity by ethanol, which is the rate-limiting step in
cholesterol biosynthesis [19]. Reports show that the diet
rich in PUFA stimulates the production of chylomicrons
by the intestine [20], this may be the reason for the in-
creased levels of cholesterol in alcohol + raw PUFA
group. Moreover, reports show that higher plasma choles-
terol levels are observed in heated oil fed group [21] and
so in alcohol + heated PUFA groups cholesterol levels
are higher.
Fielding et al. [22] have found the increased plasma TG
concentrations after acute ethanol ingestion. In vitro alco-
hol has been shown to exert a direct effect on myocardial
lipid metabolism, causing an increase in fatty acid esterifi-
cation and a decrease in oxidation, thus, accumulating TG.
The increased TG levels after PUFA ingestion may be due
to the increased availability of substrate, FFA for esteri-
fication. Since the availability of FFAs is more in heated
PUFA group, the TG levels are also comparatively higher.
Phospholipids are the vital components of biomem-
brane. They are the primary targets of peroxidation and
can be altered by ethanol [23]. The decrease in the levels of
phospholipids in liver and kidney may be due to increased
activity of phospholipases in these tissues. It has also been
suggested that the decreased levels of phospholipids are
due to increased degradation of muscle phospholipids.
Earlier studies have demonstrated that chronic exposure
to ethanol may lead to progressive increase in membrane
Pharmacological Research, Vol. 46, No. 3, 2002
phospholipase A2 activity. Jaya et al. [24] have reported
a decrease in the phospholipid content in liver and kidney
of alcohol fed rats. The increased levels in other tissues
may be due to the increased availability of FFA. Since
PUFA is a component of PL, the increased PUFA intake
may increase the levels of PL in other tissues.
The free fatty acid levels are enhanced in alcohol fed
group, which may be attributed to increased formation
of acetate, which in turn forms FFA. The increased
NADH/NAD+ ratio also favours fatty acid synthesis.
Thus, the levels of FFA are increased in liver, heart,
kidney and intestine. Increased FFA in alcohol + PUFA
(raw + heated) may be due to the increased lipid break-
down and increased dietary PUFA, may also eventually
increase the FFA levels.
Treatment of curcumin reduces the levels of lipids.
Hypocholesterolemic effect of curcumin is due to the
increased HDL formation, which transports the excess
cholesterol from extrahepatic tissues to liver where it is
catabolised [25]. Curcumin also decreases the absorp-
tion of cholesterol [26]. Reports suggest that curcumin
increases 7α-hydroxylase activities; the main enzyme
involved in the conversion of cholesterol to bile acid and
thus facilitates biliary cholesterol excretion [27].
The exact mechanism by which curcumin lowers other
lipid levels are not known, however, studies have shown
that some of the spices play a vital role in lipid metabolism,
due to their active principle. The spices are known to affect
bile acid excretion and thereby influence lipid levels. The
decreased levels of phospholipids and TG may also be due
to the decreased FFA synthesis by curcumin, which may
suppress the enzymes involved in FFA synthesis.
The levels of lipids were significantly reduced in
photo-irradiated curcumin treatment groups compared
to curcumin. Vanillin and ferulic acid, the components
of IC, due to their effective antioxidant property, protect
membrane and prevent FFA release. Being a substrate
for other lipids, FFA decrease may reflect on the levels
of lipids. Recent reports show that γ -oryzanol, a mixture
of ferulic acid can lower cholesterol level in blood and
lower the incidence of coronary heart disease. In Japan, it
has been used as a natural antioxidant in foods, beverages
and cosmetics [28]. Thus, the vanillin and ferulic acid
effectively reduce lipids by an unknown mechanism.
Fatty changes are the commonest single feature of al-
coholic liver disease. Moreover, the ingestion of alcohol
along with raw PUFA induces cytochrome P450 and
causes severe damage to liver. Thus, fatty changes of
micro and macrovesicular type, sinusoidal dilatation and
congestion were seen in alcohol + raw PUFA group. The
administration of powerful antioxidant curcumin, reduced
the extent of liver damage and so only dilatation and
microvesicular fatty changes were seen in alcohol + raw
PUFA + curcumin group.
During alcohol ingestion, fatty vacuolation will become
severe such that every hepatocyte contains a globule of
fat. The source of the hepatic fat depends on the amount
of fat in the diet. Thus, heated PUFA further potentiates
263
the effect. Histological features of alcoholic hepatitis in-
clude degenerative changes in the hepatocytes, infiltration
of polymorphonuclear leukocytes and deposition of alco-
holic hyaline. The alcohol + heated PUFA group, thus,
showed focal fatty infiltrate and feathery degeneration.
Treatment with curcumin reduced these adverse effects,
showed congestion, dilatation and fatty infiltration. The
treatment with photo-irradiated curcumin showed only
macrovesicular fatty changes, thus, proving itself more ef-
fective than curcumin.
Alcohol fed rats normally show fatty infiltration, inflam-
mation of parenchyma and vessel congestion in kidney.
Studies have shown that chronic ethanol consumption re-
sults in increased ethanol oxidation by kidney, leading to
the formation of reactive oxygen species. Alcohol + raw
PUFA group showed fatty infiltration, cloudy swelling and
congested blood vessels, which may be due to the alco-
holic effect further induced by PUFA. Only areas of focal
haemorrhage were seen in alcohol+raw PUFA+curcumin
group due to the protective role of curcumin.
Alcohol + heated PUFA group showed hyaline cast
within dilated tubule, cloudy swelling, fatty infiltration
and parenchymal inflammation, which may be attributed
to the severe toxicity of alcohol + heated PUFA. The
hyaline may act as an antigen and produce inflamma-
tory response. Curcumin being an effective antioxidant,
decreases the severity. Focal fatty infiltration, cloudy
swelling and multiple areas of haemorrhage were seen in
curcumin treated group and only multiple areas of haem-
orrhage were seen in photo-irradiated curcumin-treated
group, thus, proving the efficacy of the later.
Thus, our results indicate that IC is more effective than
curcumin in controlling the lipid levels and maintaining
the histology.
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