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1.
J Invest Surg ; 26(1): 16-29, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22646141

ABSTRACT

PURPOSE: We aimed to investigate whether caffeic acid phenethyl ester (CAPE) prevents detrimental systemic effects of intestinal ischemia-reperfusion (IR) injury on colonic anastomotic wound healing. METHODS: This experimental study was conducted on 48 male Wistar albino rats. The rats were randomly allocated into four groups and a left colonic anastomosis was performed in all rats: (i) sham-operated group (n = 12), laparatomy without intestinal IR injury; (ii) sham + CAPE group (n = 12), identical to Group 1 except for CAPE treatment (10 µmol/kg, intravenously); (iii) intestinal IR group (n = 12), 60 min of superior mesenteric ischemia followed by reperfusion; and (iv) IR + CAPE-treated group (n = 12) (10 µmol/kg, intravenously, 30 min before the construction of colonic anastomosis). On the postoperative day 7, the rats were subjected to relaparotomy for in vivo measurement of the colonic anastomotic bursting pressure. A colonic segment including the anastomotic site was resected for histopathological evaluation and biochemical analyses. The plasma proinflammatory cytokine levels were measured. Body weight changes were examined. RESULTS: CAPE treatment significantly increased colonic anastomotic bursting pressures, and colonic anastomotic tissue hydroxyproline contents and antioxidant parameters (p < .05), and significantly decreased oxidative stress markers in colonic anastomotic tissues and plasma proinflammatory cytokine levels (p < .05). Histopathological scores were significantly better due to CAPE administration (p < .05). CONCLUSIONS: This study clearly showed that CAPE treatment prevented the delaying effects of remote IR injury on colonic anastomotic wound healing. Further clinical studies are required to determine whether CAPE has a useful role in the enhancement of gastrointestinal anastomotic wound healing during particular surgeries in which IR-induced organ injury occurs.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Caffeic Acids/therapeutic use , Colon/surgery , Phenylethyl Alcohol/analogs & derivatives , Reperfusion Injury/prevention & control , Wound Healing/drug effects , Anastomosis, Surgical , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Caffeic Acids/pharmacology , Colon/blood supply , Colon/chemistry , Cytokines/blood , Drug Evaluation, Preclinical , Hydroxyproline/analysis , Laparotomy , Male , Malondialdehyde/analysis , Mesenteric Artery, Superior/physiopathology , Oxidative Stress/drug effects , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Random Allocation , Rats , Rats, Wistar , Reperfusion Injury/etiology , Surgical Wound Dehiscence , Xanthine Oxidase/antagonists & inhibitors
2.
J Invest Surg ; 25(6): 354-65, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23215792

ABSTRACT

PURPOSE: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. METHODS: This experimental study was conducted on 48 male Wistar-albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 µmol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 µmol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. RESULTS: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p < .05), and significantly increased antioxidant parameters in the intestinal tissues (p < .05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). CONCLUSION: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.


Subject(s)
Antioxidants/therapeutic use , Caffeic Acids/therapeutic use , Intestine, Small/blood supply , Phenylethyl Alcohol/analogs & derivatives , Plant Bark , Plant Extracts/therapeutic use , Reperfusion Injury/prevention & control , Animals , Antioxidants/pharmacology , Caffeic Acids/pharmacology , Cytokines/blood , Glutathione Peroxidase/metabolism , Intestine, Small/drug effects , Intestine, Small/metabolism , Male , Malondialdehyde/metabolism , Models, Animal , Nitrates/metabolism , Oxidative Stress/drug effects , Peroxidase/metabolism , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Plant Extracts/pharmacology , Rats , Rats, Wistar , Regional Blood Flow/drug effects , Reperfusion Injury/metabolism , Xanthine Oxidase/metabolism
3.
J Invest Surg ; 25(5): 301-10, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23020270

ABSTRACT

PURPOSE: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on wound healing in left colonic anastomoses in the presence of intraperitoneal sepsis induced by cecal ligation and puncture (CLP) in a rodent model. METHODS: This experimental study was conducted on 48 male Wistar albino rats. The animals were randomly allocated into four groups and a left colonic anastomosis was performed on the day following sham operation or CLP in all rats: (i) sham-operated control group, laparatomy plus cecal mobilization (n = 12) (Group 1), (ii) sham + CAPE group, identical to Group 1 except for CAPE treatment (10 µmol/kg, intraperitoneally, 30 min before construction of the colonic anastomosis) (n = 12) (Group 2), (iii) CLP group, cecal ligation and puncture (n = 12) (Group 3), and (iv) CLP + CAPE-treated group, 10 µmol/kg, intraperitoneally, 30 min before the construction of colonic anastomosis (n = 12) (Group 4). On the postoperative day 7, the animals were subjected to relaparotomy for in-vivo measurement of the colonic anastomotic bursting pressure. A colonic segment including the anastomotic site was resected for histopathological evaluation and biochemical analyses of hydroxyproline (Hyp) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA) levels, reduced glutathione (GSH) levels, and superoxide dismutase (SOD) activity. Body weight changes were examined. RESULTS: CAPE treatment significantly increased colonic anastomotic bursting pressures (p < .05), colonic anastomotic tissue Hyp contents, and enzymatic and nonenzymatic antioxidant markers (p < .05), and significantly decreased oxidative stress parameters in colonic anastomotic tissues (p < .05). Histopathological scores were significantly better by CAPE administration (p < .05). CONCLUSION: This study clearly showed that CAPE treatment prevented the detrimental effects of intraperitoneal sepsis on colonic anastomotic wound healing. Further clinical studies are required to determine whether CAPE has a useful role in the enhancement of gastrointestinal anastomotic wound healing during particular surgeries in which sepsis-induced organ injury occurs.


Subject(s)
Anastomosis, Surgical , Caffeic Acids/pharmacology , Peritonitis/drug therapy , Peritonitis/surgery , Phenylethyl Alcohol/analogs & derivatives , Wound Healing/drug effects , Animals , Colon/drug effects , Colon/pathology , Colon/physiopathology , Colon/surgery , Disease Models, Animal , Glutathione/metabolism , Hydroxyproline/metabolism , Male , Malondialdehyde/metabolism , Peritonitis/pathology , Peritonitis/physiopathology , Peroxidase/metabolism , Phenylethyl Alcohol/pharmacology , Pressure , Rats , Rats, Wistar , Stress, Mechanical , Superoxide Dismutase/metabolism , Wound Healing/physiology
4.
J Pediatr Surg ; 45(11): 2169-74, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21034939

ABSTRACT

BACKGROUND: This study was designed to determine the role of oxidative stress, nitric oxide (NO), and glutathione-related antioxidant enzymes in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury and to evaluate the potential benefits of prophylactic clarithromycin. METHODS: One-day-old Wistar albino rat pups (N = 21) were randomly divided into 3 groups: group I (control), group II (exposed to H/R), and group III (clarithromycin + H/R). Clarithromycin was administered (40 mg/kg) subcutaneously to group III for 3 days. On the fourth day, all rats except controls were exposed to H/R and were killed at 6 hours after H/R. Histopathologic injury scores (HIS), malonyldialdehyde, glutathione (GSH), glutathione-peroxidase (GSH-Px) activities, and NO levels were measured on intestinal samples. RESULTS: Whereas there was no difference for malonyldialdehyde levels among groups, HIS and NO levels were higher in group II than groups I and III (P < .05). However, GSH and GSH-Px activities were lower in group II than groups I and III (P < .05). Clarithromycin significantly increased GSH and GSH-Px activities and reduced HIS and NO levels in group III. CONCLUSION: This study showed that oxidative stress and NO contributed to the pathogenesis of H/R-induced bowel injury and that clarithromycin had a protective effect on bowel injury owing to anti-inflammatory and antioxidant effects.


Subject(s)
Clarithromycin/administration & dosage , Enterocolitis, Necrotizing/prevention & control , Oxidative Stress/drug effects , Protein Synthesis Inhibitors/administration & dosage , Animals , Animals, Newborn , Disease Models, Animal , Dose-Response Relationship, Drug , Enterocolitis, Necrotizing/metabolism , Enterocolitis, Necrotizing/pathology , Glutathione/metabolism , Ileum/blood supply , Injections, Subcutaneous , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Lipid Peroxidation/drug effects , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Rats , Rats, Wistar , Reperfusion Injury/complications , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Treatment Outcome
5.
HPB (Oxford) ; 10(6): 459-63, 2008.
Article in English | MEDLINE | ID: mdl-19088933

ABSTRACT

OBJECTIVES: Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. SUBJECTS AND METHOD: Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. RESULTS: Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). CONCLUSION: In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

6.
Int J Colorectal Dis ; 22(3): 325-31, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16718449

ABSTRACT

BACKGROUND AND AIMS: Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a water-soluble analogue of the spin label TEMPO. As an antioxidative agent, it is a member of nitroxides, which detoxifies superoxide and possibly other toxic radicals in vivo. In this study, we aimed to investigate whether tempol prevents harmful systemic effects of superior mesenteric ischemia-reperfusion on left colonic anastomosis in rats. MATERIALS AND METHODS: Anastomosis of the left colon was performed in 30 rats that were divided into three groups each having ten animals: sham-operated control (group I), 60 min of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II), and tempol-treated group (30 mg/kg before and after the ischemia-reperfusion (group III). On postoperative day 5, all animals were killed and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of anastomotic hydroxyproline content, perianastomotic malondialdehyde, and glutathione levels. RESULTS: There was a statistically significant increase in the quantity of myeloperoxidase activity and malondialdehyde levels in group II, along with a decrease in glutathione levels, anastomotic hydroxyproline content, and bursting pressure values when compared to controls. However, all of the investigated parameters were normalized in tempol-treated animals (group III). CONCLUSION: We conclude that tempol significantly prevents harmful systemic effects of reperfusion injury on colonic anastomoses in a rat model of superior mesenteric artery occlusion.


Subject(s)
Antioxidants/pharmacology , Colon/surgery , Cyclic N-Oxides/pharmacology , Reperfusion Injury/prevention & control , Wound Healing/drug effects , Anastomosis, Surgical , Animals , Antioxidants/therapeutic use , Constriction , Cyclic N-Oxides/therapeutic use , Disease Models, Animal , Male , Mesenteric Artery, Superior/surgery , Rats , Rats, Wistar , Spin Labels
7.
World J Surg ; 31(1): 200-9, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17180567

ABSTRACT

INTRODUCTION: Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. In recent animal studies, the delaying effect of intraperitoneal sepsis on healing of colonic anastomoses has been demonstrated. In this study, we aimed to investigate the effects of PDTC on healing of colonic anastomoses in the presence of intraperitoneal sepsis induced by a rodent model of cecal ligation and puncture (CLP). METHODS: Anastomosis of the left colon was performed on the day following CLP in 30 rats that were divided into three groups: sham-operated control (laparotomy and cecal mobilization, group I, n =10), cecal ligation and puncture (CLP) (group II, n = 10), PDTC-treated group (100 mg/kg IV before construction of the colonic anastomosis) (group III, n = 10). On postoperative day 6, all animals were sacrificed, and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of colonic anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase (MPO) activity, and malondialdehyde (MDA) and glutathione (GSH) levels. RESULTS: There was a statistically significant increase in the activity of MPO and MDA levels in the CLP group (group II) along with a decrease in GSH levels, colonic anastomotic HP contents, and bursting pressure values when compared to controls (group I). However, PDTC treatment led to a statistically significant increase in the tissue HP contents, GSH levels, and colonic anastomotic bursting pressure values, along with a decrease in MPO activity and MDA levels in group III (p < 0.05). CONCLUSIONS: This study showed that PDTC treatment significantly prevented the delaying effect of CLP-induced intraperitoneal sepsis on anastomotic healing in the colon. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where sepsis-induced injury occurs.


Subject(s)
Antioxidants/pharmacology , Peritoneal Diseases/physiopathology , Pyrrolidines/pharmacology , Sepsis/physiopathology , Thiocarbamates/pharmacology , Wound Healing/drug effects , Anastomosis, Surgical , Animals , Cecum/surgery , Disease Models, Animal , Glutathione/analysis , Ligation , Lipid Peroxidation , Male , Punctures , Rats , Rats, Wistar
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