Farklı hesperidin dozları, nonsteroid antiinflamatuar ilaç ve düşük molekül ağırlıklı heparinin intraplevral yapışıklığı önleme üzerine etkilerinin araştırılması: Sıçan deney modeli
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Dosyalar
Tarih
2021
Yazarlar
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Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
İntraplevral adezyonların hepsi önceden geçirilmiş cerrahi ile ilişkili olmasa da, çoğunlukla büyük ya da küçük bir cerrahi travma sonucu oluşmaktadır. Oluşan hasar veya yoğun inflamatuar süreçler sonrasında, inflamatuar eksuda ve fibrinin yetersiz fibrinolizin sonucu meydana geldiği düşünülmektedir. Cerrahi travmayı en aza indirmek için dokulara nazik davranmak ve daha noninvaziv tekniklerin kullanılması gibi önlemlere rağmen az ya da çok bu adezyonlar meydana gelmektedir. Günümüzde teknoloji ve tıp alanındaki hızlı gelişim, görüntüleme yöntemlerini ve dolayısıyla erken tanı ve tedavi stratejilerini etkilemiştir. Bu da akciğer kanseri ve toraks dışı kanserlerin akciğere olan metastazlarının daha duyarlı ve erken bir şekilde saptanması olarak iyi yönde etkilerini göstermiştir. Böylece hastaların surviyi uzamış, kanser geni taşıyan, genetik olarak yatkın bu hastalarda, ileriki dönemlerde de metastaz ve/ veya ikinci primer akciğer kanseri görülme olasılığının arttığı görülmüştür. Bu bağlamda retorakotomilerle eskiye göre daha sık karşılaşılmaktadır. Yapılan çalışmalar ve klinik tecrübelerimiz, toraksa yapılan her cerrahi girişimin az ya da çok yapışıklığa neden olduğunu göstermektedir. Bu adezyonlar, özellikle belirli bir zaman sonra yapılan retorakotomilerde ameliyat süresini uzatmakta, ciddi morbidite ve mortaliteye neden olmaktadır. Postoperatif adezyonların oluşumunu önlemek için, başta batın cerrahisi olmak üzere göğüs cerrahisi açısından da, steroidlerden kolajenlere kadar inorganik ya da organik, farklı etki mekanizmalarına sahip, sistemik uygulanabilen ya da bariyer yöntem olarak pek çok ajan üzerinde çalışmalar yapılmıştır. Bu nedenle adezyon önleyici, kolay ugulanabilen, güvenilir ve uygun maliyetli ajanların arayışı halen devam etmektedir. Hesperidin; meyvelerde, yapraklı sebzelerde, bitki köklerinde, baharatlarda, tohumlarda, çayda, kahvede bulunan doğal flavinoidlerden biridir. Vitamin E' ye benzer etkileri olan potent bir antioksidandır; ayrıca antiinflamatuar, antiviral, antimikrobiyal, antialerjik, antineoplastik, antidiyabetik vb. etkilerinin pekçok biyolojik ve farmakolojik özellik gösterdiği belirtilmiştir. Nonsteroid antiinflamatuar ilaçlar (NSAİİ), analjezik ve antiinflamatuar etkilerini, siklooksijenaz enzim inhibisyonu sonucu prostaglandin sentezini inhibe ederek oluştururlar. Tenoksikam, nonsteroid antiinflamatuar ilaçların oksikam sınıfından, bir tienotiazin türevi olup, uzun yarı ömürlü (60-75 saat) ve vücuttan en yavaş elimine edilen ve en uzun etki süreli analjeziklerden biridir. Düşük molekül ağırlıklı heparin (DMAH/ Enoksaparin), faktör Xa' yı inhibe ederek adezyon patogenezinin erken safhalarında meydana gelen antitrombotik aktiviteleri nedeniyle koagulasyon gelişiminin engellenmesi, dolayısıyle adezyon oluşumunu önlemede başarılı olabileceği düşünülerek yapılan çalışmalar mevcuttur. Çalışmamızda sıçan deney modelinde oluşturulacak intraplevral adezyonların; son dönemde farklı disiplinlerdeki çalışmalarda sık kullanılan hesperidin ile günlük rutinde kullanılan tenoksikam ve enoksaparininin antifibrotik ve antiinflamatuar etkilerini araştırmayı amaçladık. Bu amaçla çalışmamızda; aynı koloniden, 52 adet Wistar-Albino cinsi, sağlıklı erişkin erkek sıçan, rastgele 6 gruba ayrılarak incelendi; sham grubu (grup 1), cerrahi kontrol grubu (grup 2), düşük doz hesperidin grubu (grup 3), yüksek doz hesperidin grubu (grup 4), nsaii/ tenoksikam grubu (grup 5) ve dmah/ enoksaparin grubu (grup 6). Deneklere sol torakotomi yapılarak, sham grubu dışındakilere adezyon modeli uygulandı. Postoperatif 10 gün boyunca; sham grubu dışındaki gruplara, hergün aynı saatte protokolde belirtilen ilaçlar intraperitoneal olarak uygulandı. 3 sıçan, enfeksiyona bağlı ölüm nedeniyle çalışma dışında bırakıldı. Postoperatif 11. günde; sıçanlar sakrifiye edilerek kanda, IL- 1β ve IL-10 düzeyleri; makroskobik olarak plevral adezyon alanı (mm2) ve adezyon şiddet skoru; mikroskobik olarak da; mezotel hücre tabakasının bütünlüğünü göstermek için mezotal hücre proliferasyon skoru, plevral yüzeyin/yapışık akciğer dokusunun altındaki kollagen tabakasındaki mononükleer inflamatuar hücre (MNH) sayısı için MNH infiltrasyon skoru , kollagen tabakasındaki makrofajlar için makrofaj infiltrasyon skoru hesaplanarak değerlendirildi. Deneklerin; Makroskobik incelemesinde; plevral adezyon; adezyon alanı (mm2) ve adezyon şiddet skoru (AŞS) ile değerlendirildi. En az adezyon alanı (mm2) ve en düşük adezyon şiddet skoru (AŞS) enoksaparin grubunda (grup 6) bulundu. Hem adezyon şiddet skoru hem de adezyon alanı için cerrahi kontrol grubu (grup 2) ile enoksaparin grubu (grup 6) ve düşük doz hesperidin grubu (grup 3) ile enoksaparin grubu (grup 6) arasında; yine sadece adezyon alanı için tenoksikam grubu (grup 5) ile enoksaparin grubu (grup 6) arasında istatistiksel olarak anlamlı farklılık saptandı (p<0.05). Histopatolojik incelemelerde ise; mezotel hücre proliferasyon skoru incelendiğinde; cerrahi kontrol (grup 2) ve tenoksikam (grup 5) grupları arasında; mononükleer inflamatuar hücreler (MNH) için infiltrasyon skoru; incelendiğinde de sham(grup1) ve yüksek doz hesperidin (grup 4) grupları arasında da açısından istatistiksel olarak anlamlı farklılık saptandı (p<0.05). Deneklerin kanlarındaki IL- 1β ve IL-10 seviyelerinde istatistiksel olarak anlamlı farklılık saptanmadı (p>0.05). Çalısmamızın sonuçlarına göre; enoksaparin, tenoksikam ve yüksek doz hesperidinin adezyonu önlemek için farklı noktalarda etki ettiklerini gösterdik.
Although not all intrapleural adhesions are related to previous surgery, they mostly occur as a result of a major or minor surgical trauma. Inflammatory exudate and fibrin are thought to occur as a result of inadequate fibrinolysis after damage or intense inflammatory processes. Despite precautions such as being gentle on tissues and using more non-invasive techniques to minimize surgical trauma, more or less these adhesions occur. Today, rapid development in technology and medicine has affected imaging methods and therefore early diagnosis and treatment strategies. This has shown its positive effects as a more sensitive and early detection of lung cancer and non-thoracic cancer metastases to the lung. Thus, it has been observed that the possibility of metastasis and / or second primary lung cancer in these patients who are genetically susceptible, who carry cancer gene and who have prolonged survival, increase in the future. In this context, rethoracotomies are more common than before. Our studies and clinical experience show that every surgical procedure performed on the thorax causes more or less adhesion. These adhesions prolong the operation time, especially in rethoracotomies performed after a certain period of time, and cause serious morbidity and mortality. In order to prevent the formation of postoperative adhesions, studies have been carried out on many agents, from steroids to collagen, inorganic or organic, with different mechanisms of action, which can be applied systemically or as barrier methods, especially in terms of abdominal surgery and thoracic surgery. Therefore, the search for anti-adhesion, easy-to-apply, reliable and cost-effective agents still continues. Hesperidin; it is one of the natural flavinoids found in fruits, leafy vegetables, plant roots, spices, seeds, tea and coffee. It is a potent antioxidant with similar effects to Vitamin E; also anti-inflammatory, antiviral, antimicrobial, antiallergic, antineoplastic, antidiabetic etc. It has been stated that its effects have many biological and pharmacological properties. Nonsteroidal anti-inflammatory drugs (NSAID) produce their analgesic and anti-inflammatory effects by inhibiting prostaglandin synthesis as a result of cyclooxygenase enzyme inhibition. Tenoxicam is a thienothiazine derivative from the oxicam class of nonsteroidal anti-inflammatory drugs, with a long half-life (60-75 hours) and one of the slowest and longest acting analgesics that are eliminated from the body. There are studies considering that low molecular weight heparin (LMWH / Enoxoparin) may be successful in preventing the development of coagulation due to its antithrombotic activities occurring in the early stages of adhesion pathogenesis by inhibiting factor Xa. In our study, intrapleural adhesions to be formed in rat experimental model; we aimed to investigate the antifibrotic and anti-inflammatory effects of hesperidin, which are frequently used in studies in different disciplines, and tenoxicam and enoxaparin, which are used in daily routine. In our work for this purpose; from the same colony, 52 adult male Wistar-Albino rats were randomly divided into 6 groups; sham group (group 1), surgical control group (group 2), low dose hesperidin group (group 3), high dose hesperidin group (group 4), nsaii / tenoxicam group (group 5) and dmah / enoxaparin group (group 6) . The subjects were left thoracotomy and the adhesion model was applied to those except the sham group. Postoperatively for 10 days; the drugs specified in the protocol were administered intraperitoneally at the same time every day, except for the sham group. 3 rats were excluded due to infection. On the postoperative 11th day; rats were sacrificed Levels of IL-1β and IL-10 in the blood; Macroscopically pleural adhesion area (mm2) and adhesion severity score; Microscopically; Mesotal cell proliferation score to show the integrity of the mesothelial cell layer, MND infiltration score for the number of mononuclear inflammatory cells (MND) in the collagen layer beneath the pleural surface / adherent lung tissue, The macrophage infiltration score for macrophages in the collagen layer was calculated and evaluated. The subjects; In its macroscopic examination; Pleural adhesion; Adhesion area (mm2) and adhesion severity score (ASS) were evaluated. The least adhesion area (mm2) and the lowest adhesion severity score (ASS) were found in the enoxaparin group (group 6). Between the surgical control group (group 2) and the enoxaparin group (group 6) and the low dose hesperidin group (group 3) and the enoxaparin group (group 6) for both the adhesion severity score and the area of adhesion; again, a statistically significant difference was found between the tenoxicam group (group 5) and the enoxaparin group (group 6) only for the adhesion area (p <0.05). In histopathological examinations; When the mesothelial cell proliferation score is examined; between surgical control (group 2) and tenoxicam (group 5) groups; İnfiltration score for mononuclear inflammatory cells (MND); when examined, a statistically significant difference was found between the sham (group1) and high dose hesperidin (group 4) groups (p <0.05). There was no statistically significant difference in IL-1β and IL-10 levels in the blood of the subjects (p> 0.05). According to the results of our study; we have shown that enoxaparin, tenoxicam and high-dose hesperidin act at different points to prevent adhesion.
Although not all intrapleural adhesions are related to previous surgery, they mostly occur as a result of a major or minor surgical trauma. Inflammatory exudate and fibrin are thought to occur as a result of inadequate fibrinolysis after damage or intense inflammatory processes. Despite precautions such as being gentle on tissues and using more non-invasive techniques to minimize surgical trauma, more or less these adhesions occur. Today, rapid development in technology and medicine has affected imaging methods and therefore early diagnosis and treatment strategies. This has shown its positive effects as a more sensitive and early detection of lung cancer and non-thoracic cancer metastases to the lung. Thus, it has been observed that the possibility of metastasis and / or second primary lung cancer in these patients who are genetically susceptible, who carry cancer gene and who have prolonged survival, increase in the future. In this context, rethoracotomies are more common than before. Our studies and clinical experience show that every surgical procedure performed on the thorax causes more or less adhesion. These adhesions prolong the operation time, especially in rethoracotomies performed after a certain period of time, and cause serious morbidity and mortality. In order to prevent the formation of postoperative adhesions, studies have been carried out on many agents, from steroids to collagen, inorganic or organic, with different mechanisms of action, which can be applied systemically or as barrier methods, especially in terms of abdominal surgery and thoracic surgery. Therefore, the search for anti-adhesion, easy-to-apply, reliable and cost-effective agents still continues. Hesperidin; it is one of the natural flavinoids found in fruits, leafy vegetables, plant roots, spices, seeds, tea and coffee. It is a potent antioxidant with similar effects to Vitamin E; also anti-inflammatory, antiviral, antimicrobial, antiallergic, antineoplastic, antidiabetic etc. It has been stated that its effects have many biological and pharmacological properties. Nonsteroidal anti-inflammatory drugs (NSAID) produce their analgesic and anti-inflammatory effects by inhibiting prostaglandin synthesis as a result of cyclooxygenase enzyme inhibition. Tenoxicam is a thienothiazine derivative from the oxicam class of nonsteroidal anti-inflammatory drugs, with a long half-life (60-75 hours) and one of the slowest and longest acting analgesics that are eliminated from the body. There are studies considering that low molecular weight heparin (LMWH / Enoxoparin) may be successful in preventing the development of coagulation due to its antithrombotic activities occurring in the early stages of adhesion pathogenesis by inhibiting factor Xa. In our study, intrapleural adhesions to be formed in rat experimental model; we aimed to investigate the antifibrotic and anti-inflammatory effects of hesperidin, which are frequently used in studies in different disciplines, and tenoxicam and enoxaparin, which are used in daily routine. In our work for this purpose; from the same colony, 52 adult male Wistar-Albino rats were randomly divided into 6 groups; sham group (group 1), surgical control group (group 2), low dose hesperidin group (group 3), high dose hesperidin group (group 4), nsaii / tenoxicam group (group 5) and dmah / enoxaparin group (group 6) . The subjects were left thoracotomy and the adhesion model was applied to those except the sham group. Postoperatively for 10 days; the drugs specified in the protocol were administered intraperitoneally at the same time every day, except for the sham group. 3 rats were excluded due to infection. On the postoperative 11th day; rats were sacrificed Levels of IL-1β and IL-10 in the blood; Macroscopically pleural adhesion area (mm2) and adhesion severity score; Microscopically; Mesotal cell proliferation score to show the integrity of the mesothelial cell layer, MND infiltration score for the number of mononuclear inflammatory cells (MND) in the collagen layer beneath the pleural surface / adherent lung tissue, The macrophage infiltration score for macrophages in the collagen layer was calculated and evaluated. The subjects; In its macroscopic examination; Pleural adhesion; Adhesion area (mm2) and adhesion severity score (ASS) were evaluated. The least adhesion area (mm2) and the lowest adhesion severity score (ASS) were found in the enoxaparin group (group 6). Between the surgical control group (group 2) and the enoxaparin group (group 6) and the low dose hesperidin group (group 3) and the enoxaparin group (group 6) for both the adhesion severity score and the area of adhesion; again, a statistically significant difference was found between the tenoxicam group (group 5) and the enoxaparin group (group 6) only for the adhesion area (p <0.05). In histopathological examinations; When the mesothelial cell proliferation score is examined; between surgical control (group 2) and tenoxicam (group 5) groups; İnfiltration score for mononuclear inflammatory cells (MND); when examined, a statistically significant difference was found between the sham (group1) and high dose hesperidin (group 4) groups (p <0.05). There was no statistically significant difference in IL-1β and IL-10 levels in the blood of the subjects (p> 0.05). According to the results of our study; we have shown that enoxaparin, tenoxicam and high-dose hesperidin act at different points to prevent adhesion.
Açıklama
Anahtar Kelimeler
Enoksaparin, Tenoksikam, Yüksek doz hesperidin, Enoxaparin, Tenoxicam, High-dose hesperidin
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Sarıçoban, B. (2021). Farklı hesperidin dozları, nonsteroid antiinflamatuar ilaç ve düşük molekül ağırlıklı heparinin intraplevral yapışıklığı önleme üzerine etkilerinin araştırılması: Sıçan deney modeli. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Cerrahi Tıp Bilimleri Bölümü Kalp ve Damar Cerrahisi Anabilim Dalı, Konya.
