j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 9 3 e9 9

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journal homepage: www.JournalofSurgicalResearch.com

Peritoneal lavage with povidone-iodine solution

in colorectal cancereinduced rats

Hua-Li Song, MM,a Dong-Mei Zhang, PhD,b,* Heng Wen, MM,c

Meng Wang, MM,b Na Zhao, MM,b Yu-Hua Gao, MM,b and Ni Ding, MMa
a
Department of Anesthesiology, Ningxia Medical University, Yinchuan, Ningxia, China
b
Department of Anesthesiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
c
Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University,
Hangzhou, Zhejiang, China

article info abstract

Article history: Background: Although peritoneal lavage with povidone-iodine (PVPI) is frequently per-
Received 6 November 2017 formed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal
Received in revised form epithelial barrier are unknown. The purpose of this study was to investigate the effects of
3 February 2018 abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer
Accepted 27 February 2018 (CRC)einduced rat model.
Available online 25 April 2018 Materials and methods: The CRC model was induced in rats with azoxymethane and dextran
sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three
Keywords: groups (n ¼ 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl),
Peritoneal lavage and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure
Povidone-iodine was continuously monitored throughout the experiment. The levels of plasma endotoxin
Intestinal mucosa barrier and D-lactate, blood gases, and protein concentration were measured. The ultrastructural
Shock changes of the epithelial tight junctions were observed by transmission electron
microscopy.
Results: The mean arterial pressure after peritoneal lavage was lower in the PVPI group than
that in the NS group. The protein concentration and levels of endotoxin and D-lactate were
higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment
resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared
with NS rats.
Conclusions: Peritoneal lavage with PVPI dramatically compromises the integrity of the in-
testinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical
applications to include peritoneal lavage with PVPI in colorectal operations.
ª 2018 Elsevier Inc. All rights reserved.

Introduction Peritoneal lavage is frequently performed after the surgeries

of the gastrointestinal tract.2,3 Povidone-iodine (PVPI) is a
Colorectal cancer (CRC) is the third most common cancer and polymer of iodine complexed with polyvinylpyrrolidone (PVP)
the fourth most common cause of cancer death worldwide. and exhibits antiseptic and tumoricidal benefits.4 PVPI is the
The main cornerstone of treatment for CRC is surgery.1 most common iodophor and is available globally. PVP can

* Corresponding author. Department of Anesthesiology, General Hospital of Ningxia Medical University, Yinchuan Shengli Road #1160,
Yinchuan 750004, Ningxia, China. Tel.: þ86 13995086686; fax: þ86 09514073090.
E-mail address: zdm_ych@hotmail.com (D.-M. Zhang).
0022-4804/$ e see front matter ª 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jss.2018.02.055
94 j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 9 3 e9 9
form stable complexes with iodine, which is slowly released to
the environment as free iodine with concomitant bactericidal
activity.5 In addition, a previous study demonstrated that PVPI
had an antitumoral effect on colon cancer cells,6 and this ef-
fect is associated with the superoxide dismutase activity that
is caused by the oxidizing effects of its free iodine.7 For these
reasons, PVPI has been widely popularized for clinical use as a
therapeutic agent for the purpose of minimizing post-
operative septic complications and reducing cancer recur-
rence.8 Although PVPI possesses a broad spectrum
microbicide against bacteria and is lethal to CRC cells, concern
about its potential toxicity still remains. Peritoneal fibrosis has
been reported after intraperitoneal lavage with PVPI in clinical
practice.9 However, if PVPI is administered after the induce-
ment of appendicitis-peritonitis, the survival of dogs is abso-
lutely shortened.10 Moreover, other experimental studies have
demonstrated that PVPI solution results in high mortality and
causes serious peritoneal damage.11,12 We hypothesized that
peritoneal lavage with PVPI may compromise the integrity of
intestinal mucosal barrier. However, until now the effects of
PVPI on the intestinal epithelial barrier have rarely been
investigated. Therefore, the aim of the present study was to
determine the effects of abdominal irrigation with PVPI on the
intestinal epithelial barrier in a CRC-induced rat model.
Materials and methods
Rats
Five-wk-old male Sprague-Dawley rats were purchased from
the Laboratory Animal Center of Ningxia Medical University
(Yinchuan, China). The rats were maintained under controlled
conditions of humidity (50  10%), light (12 h light/12 h dark),
and temperature (23  2 C) according to the Institutional
Animal Care Guidelines. All experiments were approved by
the Animal Care and Use Committee of Ningxia Medical
University.
Rat model of CRC and grouping
The rat model of CRC was created as previously described.13,14
A total of 24 male Sprague-Dawley rats were subjected to a
single intraperitoneal injection of azoxymethane (AOM)
(15 mg/kg, SigmaeAldrich Chemical Co, St. Louis, MO) at 5 wk
of age. After the administration of the injection, the animals
were exposed to three cycles of 3% dextran sodium sulfate (MP
Biomedicals, Aurora, OH) in the drinking water for 7 d and
Fig. 1 e Experimental schedule. Rats at 5 wk of age were given a subcutaneous injection of AOM at 15 mg/kg body weight
(black arrow). One wk after the AOM injection they were given three cycles of 3% dextran sodium sulfate (black box) in
drinking water for 1 wk and normal drinking water for 2 wk.
normal drinking water for the subsequent 14 d (Fig. 1). All rats
were randomly divided into three groups at week 16: (1) a
sham group with no intraperitoneal lavage (n ¼ 8), (2) an NS
group with peritoneal lavage with 7 mL/kg of warm saline
(0.9% NaCl, 37 C) solution (n ¼ 8), (3) a PVPI group with peri-
toneal lavage with 7 mL/kg of warm 0.45%-0.55% PVPI (37 C;
n ¼ 8).12
Surgical procedures
At the end of week 16, rats were anesthetized with an
intraperitoneal injection of 2% sodium pentobarbital (60 mg/
kg). Ventilation was maintained with a ventilator (VT ¼ 6.0-
7.0 mL, respiratory rate ¼ 70 bpm, I:E ¼ 1:2). After anesthesia,
the caudal vein and the right carotid artery were isolated
and cannulated with sterile polyethylene catheters (PE-50).
All surgical procedures were performed under sterile con-
ditions. The catheter was placed in the caudal vein for the
drug administration and fluid supplement (4 mL/kg/h). The
heart rate and mean arterial pressure (MAP) were continu-
ously monitored by connecting the right carotid artery
catheter to a pressure transducer and a computerized
physiograph (BL-420S; Techman Soft, Chengdu, China).
Then, a laparotomy was performed through a 2.0 cm midline
incision followed by peritoneal lavage for 3 min. The irrigant
solution was dispersed into the abdominal cavity after
abdominal massage for 30 s as previously described. Sub-
sequently, the irrigant fluid was suctioned out, and the
wound was then aseptically covered with gauze. The irri-
gant fluid and blood samples were collected for biochemical
analyses before the peritoneal lavage and at 30 min after the
peritoneal lavage.
Blood gas analysis
Arterial blood samples were collected at the baseline and
30 min after the peritoneal lavage. Approximately 200 mL of
carotid blood was used for the measurement of potential of
hydrogen (pH), the base excess (BE), HCO‾3, and the blood
lactate level (i-STAT 300 G Blood Gas Analyzer; Abbott, Denver,
CO).
Protein concentration measurement
Protein concentration was determined with a BCA protein
assay kit (KeyGen Biotech, Nanjing, China) using bovine
plasma albumin as the standard. Before irrigation and 30 min
 song et al  povidone-iodine and colorectal cancer 95

after irrigation, the peritoneal fluid was sampled to calculate
the protein concentration.
Measurement of plasma endotoxin levels
Blood samples from the portal vein were stored in
endotoxin-free tubes for endotoxin determination. The
plasma endotoxin was measured with a limulus ameobatic
lysate test using enzyme-linked immunosorbent assay kits
(purchased from Elisa Biotech Co, Ltd, Shanghai, China)
according to the instructions. The method has a sensitivity
of 1.0 EU/mL.
Statistical analysis
All data were analyzed with IBM SPSS Statistics version 23 and
are expressed as mean  standard deviation. One-way anal-
ysis of variance was used to determine the significant differ-
ences between the different groups. Analysis of the
differences within groups was performed using analysis of
variance with repeated measures. The value of P <0.05 was
considered to be statistically significant for all tests.
Results

Measurement of plasma D-lactate levels Hemodynamic parameters

The plasma from the blood samples from the portal vein was
assayed for the D-lactate concentration by an enzymatic
spectrophotometric method with a D-lactate enzyme-linked
immunosorbent assay kit (Elisa Biotech Co, Ltd). The sensi-
tivity of this assay is 1.0 mmol/L.
Transmission electron microscopy
Specimens of the small intestine (1 mm2) were cleaned with
ice-cold phosphate buffer saline and fixed with 2% glutaral-
dehyde for 2 h. Then, tissues of the small intestine were
postfixed with 1% osmium tetroxide. Subsequently, the
specimens were dehydrated with graded ethanol and
embedded in epoxy propane. Ultrathin sections were cut and
stained with uranyl acetate and lead citrate. Finally, the ul-
trastructure of the small intestine was examined with a
transmission electron microscope (Hitachi H-7650, Hitachi,
Naka, Japan).
The MAP values after peritoneal lavage were calculated and
are presented in Figure 2. There were no significant differ-
ences in the MAP values at the baseline in any animals. After
the lavage administration, the MAP of the PVPI-treated rats
decreased to 39.44  6.81 mm Hg, which was significantly
lower than the values of the sham- and NS-treated rats at all
time points (P <0.05, Fig. 2). However, there were no significant
differences between the sham group and the NS group after
peritoneal lavage (Fig. 2). These findings indicate that perito-
neal lavage with PVPI elicited persistent hypotension.
Blood gas analysis
The pH, BE, and HCO 3 values were significantly decreased
30 min after peritoneal lavage with PVPI compared with the
sham and NS group (Table). Moreover, the lactic acid content
in the PVPI group increased to 6.61  0.77 mmol L1, which
was significantly higher than the values in the sham and NS

Fig. 2 e Effects of PVPI on the MAP after peritoneal lavage. (A) Temporal trends in mean arterial pressure. (B) Changes in
mean arterial pressure after peritoneal lavage. The data are presented as the means ± the standard errors of the mean (n [ 8
for each group). *P <0.05 versus the zero point of the same group; #P <0.05 versus the sham at the same time point; xP <0.05
versus the NS group at the same time point. NS [ rats exposed to warm saline irrigation; PVPI [ rats exposed to warm
povidone-iodine irrigation.
96 j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 9 3 e9 9

Table e Effect of PVPI on blood gas parameters after

peritoneal lavage.
Variables Groups Time points

Baseline 30 min after

lavage
pH Sham 7.387  0.033 7.394  0.032
NS 7.400  0.021 7.408  0.068
PVPI 7.392  0.023 7.196  0.021*,y,z
1
BE (mmol,L ) Sham 1.63  1.30 1.50  1.20
NS 1.75  1.39 1.63  1.30
PVPI 1.50  1.31 13.00  2.00*,y,z
HCO 1
3 (mmol,L ) Sham 23.05  1.50 22.71  1.54
NS 23.24  1.15 22.80  1.18
PVPI 22.98  1.05 10.56  1.05*,y,z
1
LA (mmol,L ) Sham 1.97  0.07 1.98  0.08
NS 1.96  0.08 1.98  0.06
PVPI 1.96  0.05 6.61  0.77*,y,z

Data presented as means  standard errors of the mean (n ¼ 8 for

each group).
NS ¼ rats exposed to warm saline irrigation; PVPI ¼ rats exposed to
warm povidone-iodine irrigation.
*
P <0.05 versus baseline of the same group.
y
P <0.05 versus sham at the same time point.
z
P <0.05 versus NS at the same time point.
Fig. 3 e Effects of PVPI on the protein concentration in the
peritoneal fluid after peritoneal lavage. The data are
groups (P <0.05, Table). No significant differences in the pH,
presented as the means ± the standard errors of the mean
BE, HCO 3 , or lactic acid values were observed between the
(n [ 8 for each group). *P <0.05 versus the protein
sham group and NS group that underwent lavage. There were
concentration before lavage of the same group; #P <0.05
no significant differences in the pH, BE, HCO 3 , or lactic acid
versus the sham at the same time point; xP <0.05 versus
values at baseline.
the NS group at the same time point. NS [ rats exposed to
warm saline irrigation; PVPI [ rats exposed to warm
Protein concentration measurement of peritoneal fluid povidone-iodine irrigation.

The protein concentration in the peritoneal fluid before lavage

did not differ significantly among the three groups (Fig. 3). The
protein concentration in the peritoneal fluid after lavage was
significantly higher in the PVPI group than those in the sham
and the NS groups (P <0.05, Fig. 3). Compared with the sham
and PVPI groups, the protein concentration was significantly
decreased in the NS group (P <0.05, Fig. 3).
Plasma levels of endotoxin and D-lactate
The levels of endotoxin and D-lactate in the plasma were
measured 30 min after peritoneal lavage (Fig. 4A and B). The
peritoneal lavage with PVPI resulted in significantly higher
levels of endotoxin and D-lactate compared with the values
observed in the sham and NS groups (P <0.05, Fig. 4A and B).
The levels of endotoxin and D-lactate were markedly lower in
the NS group than in the PVPI group after peritoneal lavage
(P <0.05, Fig. 4A and B).
Morphological ultrastructure analysis of small intestines
As tight junctions (TJs) contribute to the maintenance of the
intestinal mucosa barrier permeability, the ultrastructural
changes of intracellular TJs were observed with the
transmission electron microscopy. In the sham group, the TJs
and desmosome were intact and clear between adjoining
cells, and epithelial cell surface microvilli were arranged in
neat rows (Fig. 5A). After PVPI treatment, the TJs were
obscured or had disappeared. Moreover, the paracellular
spaces were wider (Fig. 5C), and the microvilli were damaged
and sparse with irregular lengths and arrangements (Fig. 5C).
In the NS-treated rats, the TJ and microvilli morphologies
exhibited no observable changes and remained similar to
those of the sham group (Fig. 5B).
Discussion
The results of this study confirmed that peritoneal lavage with
PVPI is harmful to CRC-induced rats and lead to significantly
more severe metabolic acidosis compared with the NS group
(P <0.05, Table). In addition, the rats that were treated with
PVPI exhibited significantly lower MAP compared with the NS
and sham groups (P <0.05, Fig. 2). When the plasma was
subsequently evaluated at 30 min after peritoneal lavage, the
levels of D-lactate and endotoxin were higher in the PVPI rats
than in the NS rats, which indicated an increased intestinal
 song et al  povidone-iodine and colorectal cancer 97

Fig. 4 e Effects of PVPI on endotoxin and D-lactate after peritoneal lavage. (A) Representative endotoxin levels from different
groups. (B) Representative D-lactate levels from different groups. The data are presented as the means ± the standard errors
of the mean (n [ 8 for each group). *P <0.05 versus sham; #P <0.05 versus NS. NS [ rats exposed to warm saline irrigation;
PVPI [ rats exposed to warm povidone-iodine irrigation.

permeability compared with the NS rats (P <0.05, Fig. 4A and
B). Moreover, the protein concentration in the peritoneal fluid
was increased in the PVPI rats (P < 0.05, Fig. 3). Taken collec-
tively, our results indicate that peritoneal lavage with PVPI can
aggravate the intestinal mucosal injury, damage TJs in the
intestinal epithelium, and even provoke endotoxin shock.
The gut barrier, which is composed of the intestinal
epithelium and intercellular TJs, can prevent pathogenic in-
testinal microorganisms, antigens, and toxins from entering
the blood. Failure of intestinal barrier function often occurs in
hemorrhage shock, severe burn injury, and surgically critical
illness and results in the increased intestinal permeability and
subsequent translocation of bacteria and endotoxins from the
gut.15 A previous study indicated that TJ proteins play a critical
role in paracellular permeability.16 Intestinal barrier
dysfunction is characterized by an increased gut permeability
and is associated with sepsis.17 When epithelial TJs are dis-
rupted, the intestinal epithelial permeability increases, which
leads to the release of bacterial endotoxins into the circula-
tion, which further aggravates septic shock.17-19
PVPI is a polymer of PVP that is complexed to iodine. The
iodine is slowly released into the environment through the
oxidative reaction in which I2 is converted to I, which con-
tributes to the bactericidal effect of PVPI.12 PVPI has long been
accepted as a disinfectant, tumoricidal agent, and a broad-
spectrum antiseptic against aerobic, anaerobic, and spore-
forming bacteria as well as against protozoa, fungi, and vi-
ruses.9 Until now, PVPI has been widely recommended for
clinical use within the contaminated peritoneal cavity and for
colorectal operations for the purpose of minimizing post-
operative septic complications and reducing cancer recur-
rence, although the advantages and side effects of PVI

Fig. 5 e Effects of PVPI on the morphological ultrastructure of the TJs after peritoneal lavage. Typical images were acquired
from sham rats (A), NS rats (B), and PVPI rats (C). The white arrows indicate epithelial cell surface microvilli, and the black
arrows indicate TJs. Scale bars [ 1000 nM. NS [ rats exposed to warm saline irrigation; PVPI [ rats exposed to warm
povidone-iodine irrigation.
98 j o u r n a l o f s u r g i c a l r e s e a r c h  a u g u s t 2 0 1 8 ( 2 2 8 ) 9 3 e9 9
compared with normal saline or water for intraperitoneal
irrigation have been debated.8,20
Exfoliated CRC cells can be detected in the intraperitoneal
fluid. A rectal washout with 5% PVPI may prevent anastomotic
and local recurrence against the implantation of viable exfo-
liated tumor cells.21 The only known tumoricidal effects of
PVPI are associated with the elimination of exfoliated cancer
cells during colorectal operations. Whether peritoneal lavage
with PVPI has the potential to affect intestinal epithelial bar-
rier is unknown. However, in the present study, we demon-
strated a clear increase in D-lactate in the PVPI rats 30 min
after peritoneal lavage compared with the NS rats. The in-
crease in D-lactate that we found in the rats that were treated
with PVPI appeared to be sufficient to increase the intestinal
permeability and led to diagnosable bacterial infections as has
been previously reported in a rat model.15,22 D-lactate is pro-
duced by the bacteria found in the gut. Generally, the D-lactate
levels in mammals are very low. When the mucosa is injured,
and the intestinal permeability is increased, the bacteria and
the products of their metabolism, including D-lactate are
released into the circulation.15,23 Treatment with PVPI
increased the endotoxin level and aggravated septic shock.
The increased in endotoxins by PVPI is mediated by bacterial
translocation due to damage to the intestinal mucosal bar-
rier.24 We do not have direct data demonstrating that the
bacteria were in the blood; however, previous study25 has
clearly demonstrated that increased intestinal permeability
results in bacterial translocation. Our present study also
demonstrated that peritoneal lavage with PVPI caused TJ
disruption. Therefore, the side effects of PVPI were possibly
due to the changes in the barrier integrity and permeability.
The development of death in the two dogs may have been
caused by PVPI. It is possible that the absorbed iodine has a
direct effect on the gastrointestinal tract.26 Moreover, we also
found that the MAP was decreased after treatment with PVPI.
This finding is supported by previous work that has reported
the increased mortality due to peritonitis after treatment with
PVPI results from an increase in the production of bacterial
endotoxins, their absorption, and the production of endotoxin
shock.20,27
A large body of evidence has associated a direct toxic effect
with the use of PVPI solutions on the peritoneum.2,5,11,12 We
found that, similar to the toxic effect of PVPI, treatment with
PVPI increases the protein concentration in the peritoneal
fluid. In addition, and similar to the report by Lores28 in PVPI-
treated dogs after peritoneal lavage, metabolic acidosis was
also found in our results as indicated by significant decreases
in the BE, pH, and HCO 3 . The lactic acid content was higher in
the PVPI group than those in the sham and NS groups. The
possible mechanism of the induction of metabolic acidosis in
the PVPI-treated rats might be due to the development of
systemic iodine toxicity through the transperitoneal absorp-
tion of iodine including the consumption of plasma-bicar-
bonate.20,29-31 Thus, we demonstrated that PVPI is unsafe for
use in the peritoneal cavity of CRC-induced rats.
Our study has some limitations. Although PVPI elicited a
side effect after peritoneal lavage, the plasma-iodine con-
centration was not determined. A future study of the plasma-
iodine concentration is needed. Second, we did not examine
the bacteria in the blood. Endotoxins are derived from the
outer membrane of gram negative bacteria, which account for
70% of intestinal bacteria.32
Conclusion
In summary, we first demonstrated that peritoneal lavage
with PVPI dramatically compromises the integrity of the in-
testinal mucosa barrier and causes an endotoxin shock by
disrupting epithelial TJs, which subsequently increases the
intestinal epithelial permeability. Our results suggest that
peritoneal lavage with PVPI is unsafe for clinical application in
colorectal operations.
Acknowledgment
Funding: This work was supported by the Ningxia Medical
University scientific research project of China, No. XZ2015021.
Authors’ contributions: D.M.Z. obtained the funding.
D.M.Z., H.W., M.W., N.Z., and Y.H.G. contributed to the
conception and design of this study. H.L.S. and D.M.Z. con-
ducted the experiments. H.L.S. and N.D. performed the data
analysis. H.L.S. and D.M.Z. wrote and revised the article. H.L.S.
D.M.Z., H.W., M.W., N.Z., Y.H.G., and N.D. contributed to final
approval of the article.
Disclosure
The authors reported no proprietary or commercial interest in
any product mentioned or concept discussed in this article.
references
1. Hermann B, Matthias K, Christian Peter P. Colorectal cancer.
Lancet. 2014;383:1490e1502.
2. Schneider RK, Meyer DJ, Embertson RM, Gentile DG,
Buergelt CD. Response of pony peritoneum to four peritoneal
lavage solutions. Am J Vet Res. 1988;49:889e894.
3. Rosato EF, Oramsmith JC, Mullis WF, Rosato FE. Peritoneal
lavage treatment in experimental peritonitis. Ann Surg.
1972;175:384e387.
4. Umpleby HC, Williamson RC. The efficacy of agents employed
to prevent anastomotic recurrence in colorectal carcinoma.
Ann R Coll Surg Engl. 1984;66:192e194.
5. Ahrenholz DH, Simmons RL. Povidone-iodine in peritonitis. I.
Adverse effects of local instillation in experimental E, coli
peritonitis. J Surg Res. 1979;26:458e463.
6. Wutzler P, Sauerbrei A, Klöcking R, Brögmann B, Reimer K.
Virucidal activity and cytotoxicity of the liposomal
formulation of povidone-iodine. Antiviral Res. 2002;54:89e97.
7. Sun P, Zhao JM, Luo ZC, et al. Diluted povidone-iodine inhibits
tumor growth through apoptosis-induction and suppression
of SOD activity. Oncol Rep. 2012;27:383e388.
8. Pattana-Arun J, Wolff BG. Benefits of povidone-iodine
solution in colorectal operations: science or legend. Dis Colon
Rectum. 2008;51:966e971.
9. Keating JP, Neill M, Hill GL. Sclerosing encapsulating
peritonitis after intraperitoneal use of povidone iodine. Aust
N Z J Surg. 1997;67:742e744.
 song et al  povidone-iodine and colorectal cancer
10. Bolton JS, Bornside GH, Cohn Jr I. Intraperitoneal povidone-
iodine in experimental canine and murine peritonitis. Am J
Surg. 1979;137:780e785.
11. Mcavinchey DJ, Mccollum PT, Mcelearney NG, Jun GM,
Lynch G. Antiseptics in the treatment of bacterial peritonitis
in rats. Br J Surg. 1983;70:158e160.
12. Kuijpers HC. Is prophylactic abdominal irrigation with
polyvinylpyrrolidone iodine (PVPI) safe? Dis Colon Rectum.
1985;28:481e483.
13. Arimura Y, Nagaishi K, Hosokawa M. Dynamics of claudins
expression in colitis and colitis-associated cancer in rat.
Methods Mol Biol. 2011;762:409e425.
14. Neufert C, Becker C, Neurath MF. An inducible mouse model
of colon carcinogenesis for the analysis of sporadic and
inflammation-driven tumor progression. Nat Protoc.
2007;2:1998e2004.
15. Sun X, Fu X, Zhang R, et al. Relationship between plasma D(-
)-lactate and intestinal damage after severe injuries in rats.
World J Gastroenterol. 2001;7:555e558.
16. Shen L, Weber CR, Raleigh DR, Yu D, Turner JR. Tight junction
pore and leak pathways: a dynamic duo. Annu Rev Physiol.
2011;73:283e309.
17. Li Z, Zhang X, Zhou H, Liu W, Li J. Exogenous
S-nitrosoglutathione attenuates inflammatory response
and intestinal epithelial barrier injury in endotoxemic
rats. J Trauma Acute Care Surg. 2016;80:
977e984.
18. Xiao G, Yuan F, Geng Y, et al. Eicosapentaenoic acid enhances
heatstroke-impaired intestinal epithelial barrier function in
rats. Shock. 2015;44:348e356.
19. Yeh YC, Yu LC, Wu CY, et al. Effects of endotoxin absorber
hemoperfusion on microcirculation in septic pigs. J Surg Res.
2017;211:242e250.
20. Lagarde MC, Bolton JS, Cohn Jr I. Intraperitoneal povidone-
iodine in experimental peritonitis. Ann Surg.
1978;187:613e619.
99
21. Mariani P, van Pelt J, Ectors N, et al. Rectal washout with
cytotoxic solution can be extended to the whole colon. Br J
Surg. 2002;89:1540e1544.
22. Smith SM, Eng RH, Campos JM, Chmel H. D-lactic acid
measurements in the diagnosis of bacterial infections. J Clin
Microbiol. 1989;27:385e388.
23. Horton JW, Walker PB. Oxygen radicals, lipid peroxidation,
and permeability changes after intestinal ischemia and
reperfusion. J Appl Physiol. 1993;74:1515e1520.
24. Wen W, Zheng H, Jiang Y, et al. Effect of intestinal epithelial
autophagy on bacterial translocation in severe acute
pancreatitis. Clin Res Hepatol Gastroenterol. 2017;41:703e710.
25. Brenchley JM, Douek DC. Microbial translocation across the GI
tract. Annu Rev Immunol. 2012;30:149e173.
26. Ndikuwera J, Winstanley EW, Binta-Mushi G, Mushi EZ.
Haematology and serum biochemistry in the racing
greyhound following intraperitoneal povidone-iodine. Vet Res
Commun. 1988;12:77e86.
27. Araujo ID, Grossi GC, Diniz SO, et al. Effects of the povidone-
iodine (PVPI) in treatment of bacterial peritonitis induced in
rats. Acta Cirurgica Brasileira. 2010;25:322e327.
28. Lores ME, Ortı́z JR, Rosselló PJ. Peritoneal lavage with
povidone-iodine solution in experimentally induced
peritonitis. Surg Gynecol Obstet. 1981;153:33e38.
29. Pietsch J, Meakins JL. Complications of povidone-iodine
absorption in topically treated burn patients. Lancet.
1976;1:280e282.
30. Berkelman R, Holland B, Anderson R. Increased bactericidal
activity of dilute preparations of povidone-iodine solutions. J
Clin Microbiol. 1982;15:635e639.
31. Miller JK, Swanson EW, Spalding GE. Iodine absorption,
excretion, recycling, and tissue distribution in the dairy cow. J
Dairy Sci. 1975;58:1578e1593.
32. Hsu CC, Wei TS, Huang CC, Chen YM. Endotoxemia is
associated with acute coronary syndrome in patients with
end stage kidney disease. BMC Nephrol. 2017;18:235.