Arch Gynecol Obstet DOI 10.1007/s00404-015-3764-4

GENERAL GYNECOLOGY

Pycnogenol prevents peritoneal adhesions Ahmet Sahbaz1 • Oner Aynioglu1 • Hatice Isik1 • Banu Dogan Gun2 Osman Cengil3 • Onur Erol4



Received: 16 December 2014 / Accepted: 26 May 2015 Ó Springer-Verlag Berlin Heidelberg 2015

Abstract Purpose This study tested the ability of pycnogenol, an extract from the bark of the French maritime pine (Pinus pinaster), to prevent intra-abdominal adhesions. Methods Thirty female Wistar albino rats were separated randomly into three equal groups: Group (1) the control group, which underwent surgery, but was given no drug; Group (2) given 10 mg/kg of pycnogenol dissolved in normal saline intraperitoneally for 10 days after surgery; and Group (3) given 0.1 mL of normal saline for 10 days intraperitoneally after surgery. On post-operative day 10,

all of the animals were killed and any adhesions were evaluated macroscopically and histopathologically. Results The macroscopic adhesion scores (mean ± SD) for Groups 1, 2, and 3 were 2.5 ± 0.53, 0.60 ± 0.70, and 2.0 ± 0.82, respectively. The macroscopic adhesion score was significantly lower in Group 2 than in Groups 1 and 3 (p \ 0.001). All three components of the histopathological evaluation (inflammation, fibrosis, and neovascularization) were significantly lower in Group 2 than in Groups 1 or 3 (p \ 0.001, p \ 0.001, and p = 0.004, respectively). Conclusions Pycnogenol was found to be effective at preventing surgery-related adhesions in an animal model.

& Ahmet Sahbaz [email protected]

Keywords Pycnogenol  Intra-abdominal  Adhesions  Female  Rat

Oner Aynioglu [email protected] Hatice Isik [email protected]

Introduction

Banu Dogan Gun [email protected]

Post-operative peritoneal adhesions are defined as pathologic fibrous connections between peritoneal surfaces and are one of the leading entities of abdomino-pelvic surgery that remains to be resolved [1, 2]. Up to 93 % of surgeries end with adhesion formation [3], devastating the patient’s life by causing pelvic pain, intestinal obstruction, or infertility, and the surgeon’s life by secondary surgeries, adhesion-related complications, and medico-legal issues [4–6]. Post-operative peritoneal adhesions also cause a large financial burden, with a reported 1.3 billion dollars per year spent on adhesion and adhesion-related problems in the USA [7]. The ethiopathogenesis of peritoneal adhesion formation is complex and involves inflammation, infection, ischemia, and oxidative stress [5, 6, 8, 9]. Disequilibrium between the coagulation and fibrinolytic systems results in improper

Osman Cengil [email protected] Onur Erol [email protected] 1

School of Medicine, Department of Obstetrics and Gynecology, Zonguldak Bulent Ecevit University, Kozlu, Zonguldak, Turkey

2

School of Medicine, Department of Pathology, Zonguldak Bulent Ecevit University, Kozlu, Zonguldak, Turkey

3

Experimental Animal Research Laboratory, School of Medicine, Zonguldak Bulent Ecevit University, Kozlu, Zonguldak, Turkey

4

Department of Gynecological Oncology, Antalya Education and Research Hospital, Antalya, Turkey

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healing and peritoneal adhesive band formation between abdomino-pelvic organs [1, 8]. Various anti-inflammatory agents (steroids, non-steroidal anti-inflammatory agents), fibrinolytic agents, antioxidant agents, and techniques have been used to prevent post-operative peritoneal adhesion formation [4, 6, 8]. However, no definitive solution has been proposed regarding peritoneal adhesion because of the sophisticated and multiple characteristics of this pathological process. Pine bark (Pinus pinaster) has been used as a medicine since ancient times [10]. Its use as an anti-inflammatory agent was mentioned by Hippocrates and it was used by Native Americans and sailors as a remedy for scurvy [10, 11]. Pycnogenol is the extract of the French maritime pine bark and is composed of catechin, phenolic acids and flavonoids [10, 12]. Recent studies have documented the use of pycnogenol in various diseases, including cardiovascular diseases and inflammatory disorders [11–14]. Additionally, its antithrombotic and vasoprotective effects have been reported [10–14]. In addition to these effects, pycnogenol is an antioxidant and antibacterial agent [10, 11, 15]. It acts as a direct antioxidant, increases the antioxidant activity of vitamin C, and protects cells against lipid peroxidation and cellular membrane disruption [10–12]. Pycnogenol, therefore, seems to be a good candidate for preventing pathological adhesion. This study was designed to test the effects of pycnogenol in terms of prevention of intra-abdominal adhesions.

Materials and methods The study was approved by the Ethics Committee on Animal Experimentation of the Faculty of Medicine of Zonguldak Bulent Ecevit University. Thirty female Wistar albino rats weighing 200 ± 50 g were used in this study. The animals were housed in stainless steel cages under controlled temperature and humidity conditions, and 12-h

dark/light cycles. All of the animals were fed with standard laboratory food and water. The animals were randomly separated into three equal groups, 10 animals in each group. After being anesthesized with 75 mg/kg ketamine (KetalarÒ 500 mg; Pfizer Ilaclari Ltd. Sti., 34347 Ortako¨y-Istanbul, Turkey), the abdomens of the animals were shaved and cleaned with povidone iodine. A vertical 3-cm midline incision was performed. The cecum was identified, and cecal abrasion was preferred as the adhesion formation process (AFP). Incisions were closed with 3/0 prolene sutures. The groups and applied procedures were as follows: Group 1: Control group. No drug was applied, and only AFP was performed. Group 2: 10 mg/kg of pycnogenol (Biotab Company, Istanbul, Turkey) were dissolved in normal saline (SFÒ; Adeka Ilac Sanayi AS, Istanbul, Turkey) and applied intraperitoneally for 10 days. Group 3: 0.1 mL of normal saline was administered for 10 days intraperitoneally. On post-operative day 10, all of the animals were killed using high-dose anesthesia (100 mg/kg, phenobarbital). Laparotomy was performed by a reverse U incision to prevent destruction of the adhesive bands. Macroscopic evaluation of the intraperitoneal cavity was performed by a surgeon who was blinded to the groups. Evans classification was used for the evaluation of post-operative peritoneal adhesions because of its ease and accuracy [16]. Evans classification scores adhesions as grade 0: no adhesion; grade 1: weak adhesive band that splits with slight force; grade 2: firm adhesive band that splits with strong force; grade 3: dense adhesive band that needs dissection with a blade or scissors (Fig. 1a–d). Following macroscopic evaluation, the adhesive lesions and cecum were excised and fixed in formaldehyde solution. After dehydration and paraffinization, 5-lm-thick sections were stained with hematoxylin and eosin (H&E). Histopathologic evaluation of specimens was performed by

Fig. 1 a No adhesion. b Grade 1 adhesion. c Grade 2 adhesion. d Grade 3 adhesion

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Arch Gynecol Obstet Table 1 Macroscopic and histological adhesion scores of the groups

Macroscopy score

Group 1

Group 2

Group 3

p

p1

p2

p3

\0.001

\0.001

0.15

0.002

\0.001

0.001

0.061

0.002

\0.001

\0.001

0.062

0.003

0.004

0.002

0.122

0.024

2.5 ± 0.53

0.60 ± 0.70

2.0 ± 0.82

0



5 (50 %)



1



4 (40 %)

3 (30 %)

2

5 (50 %)

1 (10 %)

4 (40 %)

3

5 (50 %)



3 (30 %)

Inflammation score

2.30 ± 0.68

1.0 ± 0.47

1.80 ± 0.42

0



1 (10 %)

1 (10 %)

1

1 (10 %)

8 (80 %)

1 (10 %)

2

5 (50 %)

1 (10 %)

7 (70 %)

3

4 (40 %)



1 (10 %)

Fibrosis score

2.50 ± 0.53

0.70 ± 0.68

1.90 ± 0.74

0



4 (40 %)



1



5 (50 %)

3 (40 %)

2

5 (50 %)

1 (10 %)

5 (50 %)

5 (50 %) 2.0 ± 0.82

– 0.60 ± 0.70

1 (10 %) 1.40 ± 0.70

0



5 (50 %)

1 (10 %)

1

3 (30 %)

4 (40 %)

4 (40 %)

2

4 (40 %)

1 (10 %)

5 (50 %)

3

3 (30 %)





3 Vascularization score

p Kruskal–Wallis, p1 group 1 vs. group 2, p2 group 1 vs. group 3, p3 group 2 vs. group 3

a pathologist who was unaware of the groups. Sections were evaluated under a light microscope for the degree of inflammation (grade 0: absent or normal in number; grade 1: slight increase; grade 2: moderate infiltration; grade 3: massive infiltration), fibrosis (grade 0: none; grade 1: slight; grade 2: moderate; grade 3: dense) and neovascularization (grade 0: none; grade 1: one to two vessels; grade 2: three to nine vessels; grade 3: 10 or more vessels). Statistical analysis Statistical analysis was performed using SPSS ver. 18.0 (SPSS Inc., Chicago, IL, USA). Categorical variables were presented as percentages, and continuous variables were expressed as mean ± standard deviation (SD). Comparisons among groups for numeric variables were performed using the Kruskal–Wallis test, and post hoc comparisons were performed using the Mann–Whitney U-test with Bonferroni correction. A two-sided p value of less than 0.05 was considered to indicate statistical significance.

scores are provided in Table 1. The macroscopic adhesion scores (mean ± SD) for groups 1, 2 and 3 were 2.5 ± 0.53, 0.60 ± 0.70, and 2.0 ± 0.82, respectively. The macroscopic adhesion scores were significantly lower in Group 2 than in Groups 1 and 3 (p \ 0.001). There was no significant difference between the binary comparison of Group 1 and Group 3 (p2 = 0.15). Comparisons of the paired groups are provided in Table 1. Histologic evaluation of the adhesion scores of the three groups is shown in Table 1. The inflammation scores (mean ± SD) of groups 1, 2, and 3 were 2.30 ± 0.68, 1.0 ± 0.47, and 1.80 ± 0.42, respectively. The fibrosis scores (mean ± SD) of groups 1, 2 and 3 were 2.50 ± 0.53, 0.70 ± 0.68, and 1.90 ± 0.74, respectively. The vascularization scores (mean ± SD) of groups 1, 2 and 3 were 2.0 ± 0.82, 0.60 ± 0.70, and 1.40 ± 0.70, respectively. All three components of histopathologic evaluation (inflammation, fibrosis, and neovascularization) were significantly lower in Group 2 than in Group 1 or Group 3 (p \ 0.001, p \ 0.001, and p = 0.004, respectively). Comparisons of the paired groups are shown in Table 1.

Results Discussion No animal was lost due to surgery or applied agents, and all of the animals tolerated the experiment and procedures. On post-operative day 10, all of the animals were evaluated for intra-abdominal adhesions, and macroscopic adhesion

Despite improvements in surgical technology and the increased availability of minimal access surgery, adhesions remain one of the most important problems faced by both

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surgeons and patients. The loss of integrity of the peritoneum due to bleeding, cauterization, infection, and local ischemia causes a complex and multi-step process [5, 6, 8]. Various cell types, including mesothelial cells, lymphocytes, and fibroblasts, play roles in stopping this process and repairing the peritoneal damage [8]. The cascade proceeds as inflammation, coagulation, and extracellular matrix deposition to repair the wound [8, 17]. Adhesions are the result of an improper and uncontrolled healing process due mainly to oxidative stress-related damage to peritoneal tissues. Five to seven days post-operatively, the adhesive bands turn into vascular permanent fibrous adhesions [8–17]. Hypoxia increases the production of reactive oxygen species (ROS) either directly or through nicotinamide adenine dinucleotide phosphate oxidase complex activation [18]. ROS induces fibroblasts to secrete adhesive cytokines that favor adhesion, such as tissue growth factor (TGF), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 [18, 19]. These findings also explain the histopathologic features of adhesions: histologically, adhesions are composed of highly cellular, fibrotic, highly vascular structures, and microscopic evaluation considers the following three parameters: inflammatory cells, fibrosis, and new vessel formation [20–22]. In addition to oxidative stress, fibroblasts in adhesions also express reduced levels of superoxide dismutase, caspase-3, and myeloperoxidase antioxidants [18]. Blockade of ROS production and scavenging ROS products through activation of antioxidant defense mechanisms has been shown to restore adhesive fibroblasts to normal fibroblasts, thereby decreasing cytokine and collagen production [19]. Various antioxidant agents have been evaluated in terms of their ability to prevent adhesion formation, such as vitamin C, vitamin E, N-acetyl cysteine and hypericum perforatum [23–27]. Keleidari et al. evaluated the effect of vitamin C on post-operative peritoneal adhesion, and reported better wound healing and decreased adhesion formation than in the control group [23]. Two studies have also reported the efficacy of vitamin E for prevention of post-operative peritoneal adhesion [24, 27]. Although oxidative stress-related cellular damage triggers the adhesion process, multiple steps should be targeted to prevent adhesion formation; these include inflammation, thrombosis, and the fibrinolytic system. Due to the antioxidant, anti-inflammatory, and wound healing effects of pycnogenol, we evaluated its effect on adhesion prevention. To our knowledge, this is the first study to evaluate the effect of pycnogenol on surgery-related adhesion prevention. In the present study, intra-abdominal pycnogenol administration was found to be effective in post-operative adhesion prevention. Both macroscopic adhesion scores

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and histopathologic adhesion scores were significantly reduced by pycnogenol administration. Noda et al. reported that pycnogenol is one of the most potent free radical scavenging agents [28]. Pycnogenol has been found to be comparable to vitamin E in reducing radical scavenging activity [29]. Pycnogenol inactivates superoxide and hydroxyl radicals, prevents the peroxidation of lipids, increases the lifetime and availability of ascorbic acid, and protects vitamin E from peroxidation [10, 28–30]. Pycnogenol exerts its anti-inflammatory effects through inhibition of the nuclear factor jB pathway and cyclooxygenase-1 and cyclooxygenase-2 enzymes [31–33]. It was found to be effective in reducing endometriosis-related pain in a clinical study by Maia et al. [34]. In the present study, inflammatory cell invasion was found to be significantly reduced by pycnogenol administration compared with the control group. Pycnogenol has been found to be effective in wound healing and reducing scar tissue [35, 36]. In a study by Deger et al., pycnogenol improved anastomotic colon healing in irradiated rats without adversely affecting wound healing [36]. Pycnogenol has been evaluated and found to be effective in the treatment of chronic venous ulcers through its anti-inflammatory and antithrombotic actions, and by controlling the microcirculation [12, 13]. Belcaro et al. found increased wound healing and reduced scar formation in chronic venous ulcer patients treated with pycnogenol [37]. Significantly reduced adhesive bands and fibrosis were detected following pycnogenol use in our study. Pycnogenol is generally regarded as a safe supplement, with minor reported side effects such as dizziness, diarrhea, and nausea [10–12, 38]. The manufacturers recommend a dose of 20 mg/day for its antioxidant effects, and doses range from 50 to 150 mg/day for treatment/prevention of various diseases and from 50 to 360 mg/day in clinical studies [34, 37, 38]. The lethal dose (LD50) of pycnogenol in rats is 4.2 g/kg [39]. The dose in our study was selected on a previous study [40]. Although the absence of oxidative stress markers and antioxidant status markers might seem to be a limitation in the present study, the antioxidant effect of pycnogenol has been demonstrated [28–30, 41]. In a study by Taner et al. that evaluated the effect of pycnogenol on rat sepsis induced by cecal ligation and puncture, tissue levels of oxidative stress markers were found to be significantly decreased, and the antioxidant mechanisms significantly increased, in pycnogenol-treated animals [41]. They also concluded that pycnogenol prevents oxidative stress damage, enhances the antioxidant status, and facilitates DNA repair.

Arch Gynecol Obstet

In conclusion, in an animal model, pycnogenol was found to prevent surgery-related adhesion formation primarily through its antioxidant effect. In addition to being a potent antioxidant agent, pycnogenol shows anti-inflammatory, antimicrobial, and antithrombotic effects that facilitate wound healing and adhesion prevention. Further studies are needed to evaluate the micromolecular pathways underlying the adhesion prevention effects of pycnogenol and to develop an agent that is more suitable for clinical practice. Acknowledgments We thank Assistant Professor Furuzan Kokturk, Bulent Ecevit University School of Medicine, Department of Biostatistics, for the statistical analysis of the data, and Doctor Humeyra Cicekler for her technical support. Conflict of interest

None.

References 1. De Wilde RL, Bakkum EA, Bro¨lmann H et al (2014) Consensus recommendations on adhesions (version 2014) for the ESGE adhesions research working group (European Society for Gynecological Endoscopy): an expert opinion. Arch Gynecol Obstet 290(3):581–582 2. Menzies D, Ellis H (1990) Intestinal obstruction from adhesions—how big is the problem? Ann R Coll Surg Engl 72(1):60–63 3. Weibel MA, Majno G (1973) Peritoneal adhesions and their relation to abdominal surgery. A postmortem study. Am J Surg 126(3):345–353 4. Brochhausen C, Schmitt VH, Planck CN et al (2012) Current strategies and future perspectives for intraperitoneal adhesion prevention. J Gastrointest Surg 16(6):1256–1274 5. Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL (2001) Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management. Dig Surg 18(4):260–273 Review 6. Kamel Remah M (2010) Prevention of postoperative peritoneal adhesions. Eur J Obstet Gynecol Reprod Biol 150:111–118 7. Ray NF, Denton WG, Thamer M, Henderson SC, Perry S (1998) Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994. J Am Coll Surg 186(1):1–9 8. Arung W, Meurisse M, Detry O (2011) Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol 17(41):4545–4553 9. Fletcher NM, Abuanzeh S, Saed MG, Diamond MP, Abu-Soud HM, Saed GM (2014) Nicotinamide adenine dinucleotide phosphate oxidase expression is differentially regulated to favor a prooxidant state that contributes to postoperative adhesion development. Reprod Sci 21(8):1050–1059 10. Maimoona A, Naeem I, Saddiqe Z, Jameel K (2011) A review on biological, nutraceutical and clinical aspects of French maritime pine bark extract. J Ethnopharmacol 133(2):261–277 11. Iravani S, Zolfaghari B (2011) Pharmaceutical and nutraceutical effects of Pinus pinaster bark extract. Res Pharm Sci 6(1):1–11 12. Rohdewald PA (2002) review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 40(4):158–168 Review 13. Petrassi C, Mastromarino A, Spartera C (2000) PYCNOGENOL in chronic venous insufficiency. Phytomedicine 7(5):383–388

14. Peng YJ, Lee CH, Wang CC, Salter DM, Lee HS (2012) Pycnogenol attenuates the inflammatory and nitrosative stress on joint inflammation induced by urate crystals. Free Radic Biol Med 52(4):765–774 15. Torras MA, Faura CA, Scho¨nlau F, Rohdewald P (2005) Antimicrobial activity of Pycnogenol. Phytother Res 19(7):647–648 16. Evans DM, Mc Aree K, Guyton DP (1993) Dose dependency and wound healing aspects of the use of tissue plasminogen activator in the prevention of intra-abdominal adhesions. Am J Surg 165:229–232 17. Holmdahl L, Ivarsson ML (1999) The role of cytokines, coagulation, and fibrinolysis in peritoneal tissue repair. Eur J Surg 165(11):1012–1019 18. Awonuga AO, Belotte J, Abuanzeh S, Fletcher NM, Diamond MP, Saed GM (2014) Advances in the pathogenesis of adhesion development: the role of oxidative stress. Reprod Sci 21(7):823–836 19. Fletcher NM, Jiang ZL, Diamond MP, Abu-Soud HM, Saed GM (2008) Hypoxia-generated superoxide induces the development of the adhesion phenotype. Free Radic Biol Med 45(4):530–536 20. Herrick SE, Mutsaers SE, Ozua P et al (2000) Human peritoneal adhesions are highly cellular, innervated, and vascularized. J Pathol 192(1):67–72 21. Epstein JC, Wilson MS, Wilkosz S, Ireland G, O’Dwyer ST, Herrick SE (2006) Human peritoneal adhesions show evidence of tissue remodeling and markers of angiogenesis. Dis Colon Rectum 49(12):1885–1892 22. Binnebo¨sel M, Klink CD, Serno J et al (2011) Chronological evaluation of inflammatory mediators during peritoneal adhesion formation using a rat model. Langenbecks Arch Surg 396(3):371–378 23. Keleidari B, Mahmoudieh M, Bahrami F, Mortazavi P, Aslani RS, Toliyat SA (2014) The effect of vitamin A and vitamin C on postoperative adhesion formation: a rat model study. J Res Med Sci 19(1):28–32 24. de la Portilla F, Ynfante I, Bejarano D et al (2004) Prevention of peritoneal adhesions by intraperitoneal administration of vitamin E: an experimental study in rats. Dis Colon Rectum 47(12):2157–2161 25. Chu DI, Lim R, Heydrick S et al (2011) N-acetyl-L-cysteine decreases intra-abdominal adhesion formation through the upregulation ofperitoneal fibrinolytic activity and antioxidant defenses. Surgery 149(6):801–812 26. Hızlı D, Hızlı F, Ko¨s¸ u¨s¸ A et al (2014) Effect of Hypericum perforatum on intraperitoneal adhesion formation in rats. Arch Med Sci. 10(2):396–400 27. Yetkin G, Uludag M, Citgez B, Karakoc S, Polat N, Kabukcuoglu F (2009) Prevention of peritoneal adhesions by intraperitoneal administration of vitamin E and human amniotic membrane. Int J Surg 7(6):561–565 28. Noda Y, Anzai K, Mori A, Kohno M, Shinmei M, Packer L (1997) Hydroxyl and superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system. Biochem Mol Biol Int 42(1):35–44 29. van Jaarsveld H, Kuyl JM, Schulenburg DH, Wiid NM (1996) Effect of flavonoids on the outcome of myocardial mitochondrial ischemia/reperfusion injury. Res Commun Mol Pathol Pharmacol 91(1):65–75 30. Sivonova´ M, Zitnanova´ I, Hora´kova´ L et al (2006) The combined effect of pycnogenol with ascorbic acid and trolox on the oxidation of lipids and proteins. Gen Physiol Biophys 25(4):379–396 31. Scha¨fer A, Chovanova´ Z, Muchova´ J, Sumegova´ K, Lipta´kova´ A, Durackova´ Z, Ho¨gger P (2006) Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French

123

Arch Gynecol Obstet

32.

33.

34.

35.

maritime pine bark extract (Pycnogenol). Biomed Pharmacother 60(1):5–9 Saliou C, Rimbach G, Moini H et al (2001) Solar ultravioletinduced erythema in human skin and nuclear factor-kappa-Bdependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med 30(2):154–160 Peng Q, Wei Z, Lau BH (2000) Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol Life Sci 57(5):834–841 Maia H Jr, Haddad C, Casoy J (2013) Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain. Int J Womens Health 21(6):35–39 Blazso´ G, Ga´bor M, Scho¨nlau F, Rohdewald P (2004) Pycnogenol accelerates wound healing and reduces scar formation. Phytother Res 18(7):579–581

123

¨ zer I et al (2013) The effects 36. Deg˘er KC, S¸ eker A, O of PycnogenolÒ on colon anastomotic healing in rats given preoperative irradiation. Int J Surg 11(9):983–988 37. Belcaro G, Cesarone MR, Errichi BM et al (2005) Venous ulcers microcirculatory improvement and faster healing with local use of Pycnogenol. Angiology 56(6):699–705 38. http://abc.herbalgram.org/site/DocServer/Pycnog_FullMono12080 9_LOW.pdf?docID=1741. Accessed 24 Feb 2015 39. Rodhewald P (2005) PycnogenolÒ—scientific file-section 19. Horphag Research, Geneva 40. Maritim A, Dene BA, Sanders RA, Watkins JB 3rd (2003) Effects of pycnogenol treatment on oxidative stress in streptozotocininduced diabetic rats. J Biochem Mol Toxicol 17(3):193–199 41. Taner G, Aydın S, Bacanlı M et al (2014) Modulating effects of pycnogenolÒ on oxidative stress and DNA damage ınduced by sepsis in rats. Phytother Res 28(11):1692–1700

Pycnogenol prevents peritoneal adhesions.

This study tested the ability of pycnogenol, an extract from the bark of the French maritime pine (Pinus pinaster), to prevent intra-abdominal adhesio...
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