Peritoneal adhesions are seen frequently after abdominal surgery and can cause serious complications. We aimed to evaluate the effects of the oral use of diclofenac sodium and ellagic acid on formation of postoperative adhesions in rats Studies have shown that agents with anti-inflammatory properties and antioxidant substances can prevent adhesion by decreasing oxidative stress. We compared and evaluated the effects of ellagic acid that has strong antioxidant and anti-inflammatory properties and the nonsteroidal anti-inflammatory diclofenac sodium on peritoneal adhesion development in our experimental study. Laparotomy was performed with a midline incision under general anesthesia and an adhesion model was created on the antimesenteric side of the cecum in Groups I, II, and III. Group I received 85 mg/kg ellagic acid and Group II, 50 mg/kg diclofenac sodium through the nasogastric catheter while Group III received no medication. Only laparotomy was performed in Group IV. The rats were sacrificed at the end of the 14th day. Following macroscopic scoring, tissue samples were removed and subjected to biochemical and histopathologic evaluation. The degree of adhesion and the malondialdehyde level were decreased (P < 0.05), and glutathione level increased (P < 0.05) in Group I compared to Group II and Group III. The effects of ellagic acid on the prevention of peritoneal adhesion were found to be stronger than diclofenac sodium. This can be explained by the fact that ellagic acid is a strong antioxidant and decreases oxidative stress with anti-inflammatory and anti-angiogenic effects.

Peritoneal adhesions are fibrotic adhesions that are formed intra-abdominally on the visceral or peritoneal surface during the healing of peritoneal injury.1,2  Adhesions often occur after laparotomy and are also a significant cause of postoperative morbidity.3,4  Adhesions can be asymptomatic but can also lead to serious complications such as intestinal obstruction, perforation and fistula.36 

Adhesion formation begins with mesothelial cell injury on the peritoneal membrane surface. An inflammatory process consisting of cellular elements of small venules and fibrin exudation, edema, and hyperemia begins in this region and a serous exudates develops.5,79  Fibrous bands develop between fibrinous exudate and serosal surfaces, leading to formation of fibrinous bridges. Mesothelial cells produce plasminogen activator that dissolves fibrin clots, and the fibrinolytic system is engaged causing the fibrinous exudates to be rapidly resorbed. Adhesions are formed otherwise.1012 

DS (diclofenac sodium) is a nonsteroidal anti-inflammatory agent often used in clinical practice for postoperative analgesia and is known to have a fibrinolytic effect.13,14  EA (ellagic acid) is a natural antioxidant reported to be present in walnuts, carrots, tomatoes, pomegranate, grape juice, grape wine, blueberries, blackberries, and strawberries in significant quantities.1518  EA is a phenolic acid derivative that inhibits lipid peroxidation in addition to its anti-inflammatory, antiproliferative, anti-angiogenic and anticarcinogenic effects.16,17 

We aimed to evaluate the effects of the oral use of DS that has an anti-inflammatory effect and EA that has an antioxidant effect in addition to its anti-inflammatory effect on intra-abdominal adhesion development in comparison in the present study.

This study was conducted with the permission of Kafkas University's Local Ethics Committee for Animal Experiments (KAÜ-HADYEK - 2012-31).

Animals: This study was conducted on 32 Wistar Albino female rats, 12 weeks of age, with a weight of 250 to 300 g in 4 groups with 8 animals in each group.

Group I: The EA group (85 mg/kg ellagic acid was administered orally, a daily single dose after the surgery),

Group II: The DS group (50 mg/kg diclofenac sodium was administered orally, a daily single dose after the surgery),

Group III: The control group (only an adhesion model was created but no drug was administered),

Group IV: Sham group (only laparotomy was performed).

Drug administration: Orogastric gavage was used in a daily single dose and 85 mg/kg EA (ellagic acid, Sigma-Aldrich Chemical Co., St. Louis, MO, USA) was administered to Group I, and 50 mg/kg DS (Dikloron 50 mg, tablet, DEVA, Tekirdağ, Turkey) to Group II while no drug was administered in Group III and Group IV.

Surgical procedure: Rats were kept in the laboratory environment for a week before the experiment in all study groups and were fed with ad libitum standard rat chow and water. The rats were anesthetized by using intraperitoneal 10 mg/kg xylazine HCl (Rompun 2%, Bayer, Istanbul, Turkey) and 80 mg/kg ketamine HCl (Ketasol, Interhas, Turkey) combination. The ventral abdominal area was prepared for aseptic surgery and a midline incision of 3 cm was made. The cecum was revealed in Groups I, II, and III. Its anterior wall was determined and rubbed with a gauze pad held with a clamp until serous punctate hemorrhages developed. Once the adhesion model was created, the abdomen was closed in accordance with the anatomy (Fig. 1). Only laparotomy with a midline incision was performed in the Sham group (Group IV). After completion of all procedures in each group, the abdominal wall was closed in accordance with the anatomy. The animals were housed in individual cages and were postoperatively followed. A second-generation cephalosporin was administered to the gluteal muscle for a total of 3 pre- and postoperative days.

Fig. 1

Model of adhesion: The cecum was exposed and its anterior wall rubbed with a gauze held in a clamp until serosal punctate hemorrhages developed in Groups I, II, and III.

Fig. 1

Model of adhesion: The cecum was exposed and its anterior wall rubbed with a gauze held in a clamp until serosal punctate hemorrhages developed in Groups I, II, and III.

Macroscopic evaluation: The rats were sacrificed by cervical dislocation on the 14th day under general anesthesia. A “U” incision was made in the abdomen, the abdominal wall was retracted and maximum visibility was provided. The adhesions were quantitatively evaluated and scored blindly by 2 physicians using the classification described in the literature.1820 

Grade 0: No adhesion

Grade 1: A single adhesive band between the organs or between the organ and abdominal wall (Fig. 2a)

Fig. 2

Macroscopic adhesion scoring. (a): Grade 1, (b): Grade 2, (c): Grade 3, (d): Grade 4. Grade 1: A single adhesive band between the organs or between the organ and abdominal wall (a). Grade 2: Two adhesive bands between the organs or between the organ and abdominal wall (b). Grade 3: More than two adhesive bands between the organs or between the organ and abdominal wall, or adhesions of intestinal loops with or without adhesions to the abdominal wall (c). Grade 4: Viscera directly attached to the abdominal wall (d). Model of adhesion.

Fig. 2

Macroscopic adhesion scoring. (a): Grade 1, (b): Grade 2, (c): Grade 3, (d): Grade 4. Grade 1: A single adhesive band between the organs or between the organ and abdominal wall (a). Grade 2: Two adhesive bands between the organs or between the organ and abdominal wall (b). Grade 3: More than two adhesive bands between the organs or between the organ and abdominal wall, or adhesions of intestinal loops with or without adhesions to the abdominal wall (c). Grade 4: Viscera directly attached to the abdominal wall (d). Model of adhesion.

Grade 2: Two adhesive bands between the organs or between the organ and abdominal wall (Fig. 2b)

Grade 3: More than two adhesive bands between the organs or between the organ and abdominal wall, or adhesions of intestinal loops with or without adhesions to the abdominal wall (Fig. 2c)

Grade 4: Viscera directly attached to the abdominal wall (Fig. 2d)

Biochemical evaluation: Tissue samples were taken from the area where the suture was placed in the cecum and malondialdehyde (MDA) and glutathione (GSH) measurements were performed spectrophotometrically according to the method reported by Beutler et al and Yoshioka et al (UV-1201, Shimadzu, Japan).21,22 

Histopathologic evaluation: Adhesive bands were histopathologically evaluated with the affected organs in rats with adhesions. The parietal peritoneum and anterior cecum were resected and evaluated histopathologically in rats without adhesions. 5-μ-thick sections obtained from the paraffin blocks were stained with hematoxylin-eosin (HE), evaluated under a light microscope (Leica DM4000B) and recorded (Leica DFC280). Grading of lesions was performed in 10 different fields and the same magnification (HE × 100) based on inflammatory and necrotic changes as below:

  • (−) No lesion found

  • (+) Mild lesions (<10%)

  • (++) Moderate lesions (10–50%)

  • (+++) Severe lesions (<50%)

Statistics: The SPSS version 18 software (SPSS Japan Inc.) was used for statistical analysis of all data obtained from the study. Mean and standard deviations that are the central distribution criteria were calculated with statistical analysis and the differences of nominal values between the groups were evaluated using Fisher's definite chi-square test in the analysis of nonparametric data. A P value <0.05 was considered significant. The significance of the difference between 2 groups regarding the parameters found statistically significant with the Kruskal-Wallis test was evaluated with the Whitney U test for the analysis of the values obtained by measurement. A P value <0.015 with Bonferroni correction was considered significant.

The results obtained from the study were macroscopically, histopathologically, and biochemically categorized (Table 1).

Table 1

Macroscopic, histopathologic, and biochemical results for Kruskal−Wallis H test analysis

Macroscopic, histopathologic, and biochemical results for Kruskal−Wallis H test analysis
Macroscopic, histopathologic, and biochemical results for Kruskal−Wallis H test analysis

Two animals each in Group I and Group III and 1 animal each in Group II and Group IV died in the postoperative period and these animals were not included in the evaluation. The cause of death for the rats was thought to be individual infection.

Macroscopic results

Table 1 shows the statistically significant differences between the groups according to macroscopic adhesion scoring following evaluation after relaparotomy (P < 0.050). Group I and Group II showed a significant difference when compared with the control group (Group III) but there was no significant difference between Group I and Group II.

There was a statistically significant difference between Group I and the other groups in terms of MDA (P < 0.05), but this difference was not present between Group II and Group III. However, the MDA level in Group I was lower than in Group II and Group III. There was no statistically significant difference between Group I and the other groups in terms of GSH (P > 0.05) but the values in Group I were higher than the others.

Histopathologic findings

Group I: Mild hyperemia and mild edematous changes were present in the vessels of the lamina propria in the tissues of 3 cases in the group where ellagic acid was administered (Fig. 3). Edema and hyperemia of the lamina propria was not seen in the other 2 cases. Cellular infiltration with sporadic neutrophil leukocytes was present. Fibrosis in the tunica serosa was observed in 1 case. No fibrosis was seen in the other cases. Adhesion of the liver to the Glisson capsule was seen in only 1 case in this group. None of the patients showed necrosis in the lamina propria.

Fig. 3

Inflammatory cell in filtration in submucosa (arrowheads), H&E (× 100).

Fig. 3

Inflammatory cell in filtration in submucosa (arrowheads), H&E (× 100).

Group II: Marked necrosis (Fig. 4) and accompanying neutrophil leukocyte infiltration, edematous changes, hyperemia, and capillarization were noticed in the lamina propria of 6 of 7 cases in the group where diclofenac sodium was administered. Degenerative changes in the muscles and mononuclear cells were observed in the lumen and around the vessels in particular in the submucosa. Mononuclear cell infiltrations were also found in the tunica muscularis and tunica serosa. Ovarium and adhesion were noticed in 1 case.

Fig. 4

Necrose (N) and inflammatory cell infiltration (arrowheads) in lamina propria, H&E,(× 100).

Fig. 4

Necrose (N) and inflammatory cell infiltration (arrowheads) in lamina propria, H&E,(× 100).

Group III:Large areas of necrosis spreading from the cecal lumen lamina epithelia to the tunica muscularis and intact or necrotic neutrophilic leukocyte infiltration (Fig. 5), edematous changes, hyperemia, and capillarization were noticed in 1 of the 6 cases in the control group. Thickening due to organized fibrosis was also observed in this layer in 4 cases. Mononuclear cell infiltration was found in the lamina propria, tunica muscularis (Fig. 6), and tunica serosa.

Fig. 5

Inflammatory cell infiltration in lamina propria (arrowhead) and submucosa (star), H&E (× 100).

Fig. 5

Inflammatory cell infiltration in lamina propria (arrowhead) and submucosa (star), H&E (× 100).

Fig. 6

Neutrophilic leukocytes (arrowhead) and larvae (stars), H&E (× 100).

Fig. 6

Neutrophilic leukocytes (arrowhead) and larvae (stars), H&E (× 100).

Group IV: The lesions detected in the patients in the sham group were usually limited to the lamina propria and submucosa. There was marked mononuclear cell infiltration in both layers. These cells were accompanied by a small number of neutrophilic leukocytes in the lamina propria in one case and by a granuloma in the submucosa in a different case (Fig. 7). Edematous changes were present in some places.

Fig. 7

Inflammatory cell infiltration in submucosa (arrowheads), H&E (× 100).

Fig. 7

Inflammatory cell infiltration in submucosa (arrowheads), H&E (× 100).

Intra-abdominal adhesions after surgery is a significant cause of morbidity in the short and long term and many studies have therefore focused on their prevention.3,4  Peritoneal adhesions occurring after abdominal surgery reduce the quality of life. Although adhesions are formed in almost all abdominal operations, there is almost no effective method to prevent them. The repair process as a result of any disruption of tissue integrity consists of inflammation, fibroblast proliferation, and then the maturation phase with connective tissue and matrix formation.3  We aimed to investigate the effects of EA that has many effects but is mainly antioxidant and anti-inflammatory on intra-abdominal adhesion development in comparison with DS in this study.

DS is a nonsteroidal anti-inflammatory agent used in various ways as an adhesion inhibitor.13,14  Some effects of EA have not yet been fully revealed although its antioxidant, anti-inflammatory, and anti-angiogenesis effects are known but studies on its anti-adhesive effect are limited. Furthermore, the anti-inflammatory effect of both substances is known to be through inhibition of COX-2.13,14,23  We administered the oral form of both agents a daily single dose after the surgery and compared their effects in our study.

Positive effects of DS were reported on pleural adhesions by Lisete et al and after thoracic surgery by Lardinois et al13,14  Although there are some studies on EA, we did not come across any that evaluated its effect on intraabdominal adhesion. There was a statistically significant difference between the groups regarding macroscopic classification in our study. Adhesion development was less in Group I than in Group II and Group III. Various antioxidants and substances such as hyaluronic acid have been used to prevent intra-abdominal adhesions. Another study similar to ours evaluated the effect of hyaluronic acid on adhesion with macroscopic and microscopic examination. They reported that the trauma decreased to a minimum level when the tissue was covered with hyaluronic acid before the adhesion model is created and increased hyaluronic acid viscosity led to a macroscopic and microscopic decrease of intraabdominal adhesion in rats.24 

The level of MDA, an oxidative stress parameter, has been reported to be increased in peritoneal adhesions and could be reversed to normal limits with antioxidant or anti-inflammatory agents.3,4  A significant decrease in the MDA level with EA was reported by Böyük et al in rats where intestinal ischemia developed after lung trauma and by Özkaya et al in liver toxicity.25,26  Similarly, the MDA levels showed a significant decrease in Group I compared to Group II and Group III in our study. A decrease was present in Group II compared to Group III but this was not as marked as in Group I. The level of GSH, an anti-oxidant in contrast to MDA, has been reported to decrease with ischemia, trauma or adhesions.3,4,27  No statistically significant difference was found between Group I and the other groups in terms of GSH level in our study. However, the GSH level in Group I was higher than in Group II and Group III and closer to the sham group. The decrease in the MDA level and increase in the GSH level in the group where ellagic acid was administered is significant for our study. Similarly EA was reported to reduce cardiac levels of glutathione peroxidase (GPx), catalase, tumor necrosis factor alpha (TNF alpha), and malondialdehyde significantly.17,18 

Rosillo et al reported that EA decreases inflammatory cell infiltration, edema, hyperemia, and necrosis in Crohn's disease and starts re-epithelialization during recovery, and linked this effect to the inhibition of cyclooxygenase (COX 2) and nitric oxide synthase (iNOS) activity.23  Girish et al reported a decrease in rat liver necrosis, fat accumulation, and inflammatory reactions in rats given EA after liver toxicity was created by administering carbontetrachloride in a different study.28 

Lisete et al reported that diclofenac sodium decreased leukocyte migration, edema, hyperemia, and fibrosis.13  Lardinois et al reported an anti-adhesive effect through decreasing granulation tissue, collagen deposition and fibrosis.14  We found a decrease in edema, hyperemia, inflammation, fibrosis, and adhesion in Group I as well as in Group II compared to Group III. Although a decrease was seen in Group II compared to Group III in terms of necrosis, this decrease was not as marked as in Group I. There are many products containing ellagic acid in the market but not enough information is present regarding their ingredients and side effects. Problems may arise when determining when and at what dose EA should be used. Previous studies have not clearly reported the side effects of ellagic acid.29  Side effects need to be determined according to the dose with clinical use in future periods. The clinical use of EA can also enable the determination of the rate of prevention for conditions such as intestinal obstruction, infertility, and chronic pain with patient follow-up and laparoscopic methods as necessary.

In conclusion, taking all our study data into account, the positive effects of the oral form of EA on the development of peritoneal adhesions are more marked than DS, a nonsteroidal anti-inflammatory drug. These positive effects could be a result of the strong antioxidant effect of EA reducing oxidative stress together with its anti-inflammatory and anti-angiogenesis effects. The clinical use of EA as for DS can be targeted with experimental studies performed by using different doses in line with our study.

1
Herrick
EH
,
Mutsaers
SE
,
Ozua
P
,
Sulaiman
H
,
Omer
A
,
Boulos
P
et al
.
Human peritoneal adhesions are highly cellular, innervated and vascularized
.
J Pathol
2000
;
192
(
1
):
67
72
2
Hellebrekers
BWJ
,
Trimbos-Kemper
TCM
,
Trimbos
JBMZ
,
Emeis
JJ
,
Kooistra
T
.
Use of fibrinolytic agents in the prevention of postoperative adhesion formation
.
Fertil Steril
2000
;
74
(
2
):
203
212
3
Özler
M
,
Ersöz
N
,
Özerhan
İH
,
Topal
T
,
Öter
Ş
,
Korkmaz
A
.
The effect of alpha-lipoic acid in the prevention of peritoneal adhesions
.
Turk J Gastroenterol
2011
;
22
(
2
):
190
194
4
Celepli
S
,
Kısmet
K
,
Kaptanoğlu
B
,
Erel
S
,
Özer
S
,
Celepli
P
et al
.
The effect of oral honey and pollen on postoperative intraabdominal adhesions
.
Turk J Gastroenterol
2011
;
22
(
1
):
65
72
5
Saed
GH
,
Munkarah
AR
,
Diamond
MP
.
Cyclooxygenase-2 expressed in human fibroblasts isolated from intraperitoneal adhesions but not from normal peritoneal tissues
.
Fertil Steril
2003
;
79
(
6
):
1404
1408
6
Vrijland
WW
,
Tseng
LNL
,
Eijkman
HJM
,
Hop
WCJ
,
Jakimowicz
JJ
,
Leguit
P
et al
.
Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane
.
Ann Surg
2002
;
235
(
2
):
193
199
7
Reed
KL
,
Fruin
AB
,
Bishop-Bartolomei
KK
,
Gower
AC
,
Nicolaou
M
,
Stucchi
AF
et al
.
Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation
.
J Surg Res
2002
;
108
(
1
):
165
721
8
Golan
A
,
Stolik
O
,
Wexler
S
,
Langer
R
,
Ber
A
,
David
MP
.
Prostaglandins- A role in adhesion formation
.
Acta Obstet Gynecol Scand
1990
;
69
(
4
):
339
341
9
Guvenal
T
,
Cetin
A
,
Ozdemir
H
,
Yanar
O
,
Kaya
T
.
Prevention of postoperative adhesion formation in rat uterine horn model by nimesulide: a selective COX-2 inhibitor
.
Hum Reprod
2001
;
16
(
8
):
1732
1735
10
Tito
WA
,
Sarr
MG
.
Intestinal obstruction
.
Nyhus
LM
(
ed
).
Shackleford's Surgery of the Alimentary Tract. 4th ed
.
Philadelphia
:
Saunders Co
,
1996
:
375
416
11
Dunn
RC
,
Steinleitner
AJ
,
Lambert
H
.
Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model
.
Am J Obstet Gynecol
1991
;
164
(
5 Pt 1
):
1327
1330
12
Kennedy
R
,
Costain
DJ
,
McAlister
VC
,
Lee
TDG
.
Prevention of experimental postoperative peritoneal adhesions by N,O-carboxymethylchitosan
.
Surgery
1996
;
120
(
5
):
866
870
13
Lisete
R
,
Teixeira LR, Vargas FS, Acencio M, Antonangeio L, Vaz MAC, Marchi E. Influence of antiinflammatory drugs (methylprednisolone and diclofenac sodium) on experimental pleurodesis induced by silver nitrate or talc
.
Chest
2005
;
128
(
6
):
4041
4045
14
Lardinois
D
,
Vogt
P
,
Yang
L
,
Hegyi
I
,
Baslam
M
,
Weder
W
.
Non-steroidal anti-inflammatory drugs decrease the quality of pleurodesis after mechanical pleural abrasion
.
Eur J Cardiothorac Surg
2004
;
25
(
5
):
865
871
15
Mo
J
,
Panichayupakaranant
P
,
Kaewnopparat
N
,
Songkro
S
,
Reanmongkol
W
.
Topical anti-inflammatory potential of standardized pomegranate rind extract and ellagic acid in contact dermatitis
.
Phytother Res
2013
;
28
(
4
):
629
632
16
Rogerio
AP
,
Fontanari
C
,
Borducchi
E
,
Keller
AC
,
Russo
M
,
Soares
EG
et al
.
Anti-inflammatory effects of Lafoensia pacari and ellagic acid in a murine model of asthma
.
Eur J Pharmacol
2008
;
580
(
1–2
):
262
270
17
Lee
WJ
,
Ou
HC
,
Hsu
WC
,
Chou
MM
,
Tseng
JJ
,
Hsu
SL
et al
.
Ellagic acid inhibits oxidized LDL mediated LOX-1 expression, ROS generation and inflammation in human endothelial cells
.
J Vasc Surg
2010
;
52
(
5
):
1290
1300
18
Chao
PC
,
Hsu
CC
,
Yin
MC
.
Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice
.
Nutr Metab (Lond)
2009
;
6
:
33
19
Galili
Y
,
Ben-Abraham
R
,
Rabau
M
,
Klausner
J
,
Kluger
Y
.
Reduction of surgery induced peritoneal adhesions by methylene blue
.
Am J Surg
1998
;
175
(
1
):
30
32
20
Hemadeh
O
,
Chilukuri
S
,
Bonet
V
,
Hussein
S
,
Chaudry
IH
.
Prevention of peritoneal adhesions by administration of sodium carboxymethyl cellulose and oral vitamin E
.
Surgery
1993
;
114
(
5
):
907
910
21
Beutler
E
,
Duron
O
,
Kelly
BM
.
Improved method for determination of blood glutathione
.
J Lab Clin Med
1963
;
61
:
882
888
22
Yoshioka
T
,
Kawada
K
,
Shimada
T
,
Mori
M
.
Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood
.
Am J Obstet Gynecol
1979
;
135
(
3
):
372
376
23
Rosillo
MA
,
Sanchez-Hidalgo
M
,
Cárdeno
A
,
de la Lastra
CA
.
Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn's disease
.
Biochem Pharmacol
2011
;
82
(
7
):
737
745
24
Burns
JW
,
Skinner
K
,
Colt
J
,
Sheidlin
A
,
Bronson
R
,
Yaacobi
Y
et al
.
Prevention of tissue injury and postsurgical adhesions by precoating tissues with hyaluronic acid solutions
.
J Surg Res
1995
;
59
(
6
):
644
652
25
Böyük
A
,
Onder
A
,
Kapan
M
,
Gümüş
M
,
Fιrat
U
,
Başaralι
MK
et al
.
Ellagic acid ameliorates lung injury after intestinal ischemia-reperfusion
.
Pharmacogn Mag
2011
;
7
(
27
):
224
228
26
Özkaya
A
,
Çelik
S
,
Yüce
A
,
Şahin
Z
,
Yılmaz
Ö
.
The effects of ellagic acid on some biochemical parameters in the liver of rats against oxidative stress induced by aluminum
Kafkas Univ Vet Fak Derg
2010
;
16
(
2
):
263
268
27
Jaeschke
H
.
Molecular mechanisms of hepatic ischemia reperfusion injury and preconditioning
.
Am J Physiol Gastrointest Liver Physiol
2003
;
284
(
1
):
G15
26
28
Girish
C
,
Pradhan
SC
.
Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in mice
.
J Pharmacol Pharmacother
2012
;
3
(
2
):
149
155
29
Corbett
S
,
Daniel
J
,
Drayton
R
,
Field
M
,
Steinhardt
R
,
Garrett
N
.
Evaluation of the anti-inflammatory effects of ellagic acid
.
J Perianesth Nurs
2010
;
25
(
4
):
214
220