Beneficial Effects of Quercetin on the Zone of Stasis in an Experimental Burn Model

Objective: In burn injury, the zone of stasis determines the width and depth of the necrosis. Our aim is to show the effectiveness of quercetin on the viability within the zone of stasis in burns of rats. Materials and Methods: Forty-eight rats were divided into three groups. The rats in Group 1 (control group) were only applied the comb burn model; the rats in Group 2 (post-burn group) were administered 50 mg/kg of quercetin intraperitoneally, every day after the burn procedure until euthanasia; and the rats in Group 3 (pre-burn group) were administered 50 mg/kg of quercetin intraperitoneally, every day for 7 days before and after the burn procedure until euthanasia. Results: The living tissue calculated was 85.41% (+/- 14.06) in Group 3, 40.37% (+/- 9.75) in Group 2, and 16.81% (+/- 9.4) in Group 1. The level of apoptosis was 30.0 (+/- 10.8) in Group 3, 33.8 (+/- 08.7) in Group 2, and 37.4 (+/- 11.5) in Group 1. The level of autophagy was 49.50 (+/- 8.58) in Group 3, 27.17 (+/- 5.53) in Group 2, and 21.00 (+/- 5.66) in Group 1. All the differences between the groups were statistically significant (p< 0.01). Conclusion: Quercetin reduces apoptosis and increases autophagy, thereby increasing tissue viability in the zone of stasis of burn injury.Namik Kemal University Research Center [NKUBAP.00.20.AR.15.01]The article was supported under project NKUBAP.00.20.AR.15.01 by the Namik Kemal University Research Center

Kersetinin Ratlarda, Yanık Staz Bölgesi Üzerindeki Etkisi

Yanık tedavisinde esas amaç hasarlanan doku miktarının minimal seviyede tutmaktır. Yanık alanın genişlik ve derinliğinin miktarı hastaların mortalite ve morbiditesini belirleyen temel faktördür. Staz zonu olarak tanımlanan ve koagulasyon alanını çevreleyen alan yanık sonrası oluşacak nekrozun derinlik ve genişliğini belirleyen kritik bölgedir. Birçok ajan staz zonundaki dokularının korunması için denenmiştir. Bu deneysel çalışmada birçok değişik doku üzerinde antioksidan, antiinflamatuar ve antiapoptotik etkisi olduğu bilen kersetinin yanık staz zonu üzerindeki etkisi incelenmektedir. Çalışmada kersetin tedavisi yapılmayan, akut(yanık sonrası tedaviye başlanan) kersetin tedavisi yapılan ve kronik(yanık öncesi tedaviye başlanan) kersetin tedavisi yapılan gruplar karşılaştırıldı. Tedavi sonrası yanık yarası genişliği planimetrik ve sintigrafik olarak değerlendirildi. Ek olarak doku örnekleri alınarak malondialdehyde(MDA), myeloperoksidaz(MPO) ve nitrotirozin seviyeleri, kersetinin antiinflamatuar ve antioksidan etkisinin gösterilmesi için ölçüldü ve doku örneklerinde apoptoz ve otofaji seviyesi belirlendi. Kersetin ile tedavi edilen gruplarda nekroz miktarının ve apoptozun kontrole göre istatistiksel olarak anlamlı olacak şekilde daha az olduğu, otofajinin de kontrol grubunda, kersetin ile tedavi edilen gruplara göre istatistiksel olarak anlamlı olacak şekilde daha fazla olduğu görüldü. MDA,MPO and nitrotirozin ölçüm değerlerini bakımında gruplar arasında istatistiksel olarak anlamlı olacak şekilde bir fark tespit edilmedi. Sonuç olarak bu çalışma da kersetinin staz zonu üzerinde koruyucu etkisi olduğunu göstermiştir.Keeping the amount of damaged tissue at a minimum is one of the primary goals of treatment in burns. The width and depth of the burned area is at the top of the factors affecting mortality and morbidity in patients.The zone of stasis, the encircling area of the zone of coagulation, is a critical area which determines the depth and width of the necrosis in burns. Many agents were proposed to salvage the zone of stasis. Due to the known antioxidant, antiinflammatory and antiapoptotic effects of quercetin on multiple tissue, the effect of quercetin on saving the zone of stasis was investigated in this experimental study. No quercetin treatment, acute (treatment started after burn injury) quercetin treatment and chronic(treatment started before burn injury) quercetin treatment was compared in a rat comb-burn model. The extent of burn wounds was evaluated by planimetry and scintigraphy in the groups. Additionally, skin samples were obtained to analyze malondialdehyde (MDA), myeloperoxidase (MPO), nitrotyrosine to see antiinflamatuary and antioxidant effect of quercetin and apoptosis and autophagy levels were evaluate. Necrosis rate and apoptosis were statisticaly significant lower in quercetin treatment groups and autophagy level were statisticaly significant lower in control group. There were no difference between the groups in terms of MDA,MPO and nitrotyrosine concentrations. In conclusion, this study showed us the possible saving effect of quercetin on the zone of stasis

Effects of ionizing radiation on ovarian morphology, estrous cycle and ovulation rate in normal and superovulated mice

DoktoraÇalışmamızda, radyasyonun ovaryum morfolojisi, ovulasyon oranı ve östrus siklusu üzerine olan etkilerinin morfolojik ve morfometrik parametrelerle gösterilmesi amaçlandı. Yaklaşık 3 düzenli siklus gösteren denekler deneye alındı ve yedi grup oluşturuldu. Kontrol, radyasyon-sham, radyasyon I ve II gruplarında spontan ovulasyon; süperovulasyon, radyasyon+süperovulasyon I ve II gruplarında ise süperovulasyon oranları elde edildi. Tek doz, 7.2 Gy ve tüm vücut radyasyon uygulaması, diöstrus fazından proöstrus fazına geçiş döneminde yapıldı. Radyasyon I grubundaki deneklerden radyasyonu takip eden ilk ovulasyon döneminde, radyasyon II grubunda ise ikinci ovulasyon döneminde ampulla bölgeleri patlatılarak oositler toplandı. Radyasyon+süpeovulasyon I grubunda, radyasyonu takip eden ilk proöstrus fazında, radyasyon+süperovulasyon II grubunda ise ikinci proöstrus fazında süperovulasyon protokolü uygulandı ve oositler toplandı. Tüm gruplara ait ovaryumlar ise ışık mikroskopik inceleme için işlemlendirildi. Radyasyonun ardından ilk ovulasyon döneminde ovulasyon oranı ve ovaryum ağırlığı kontrol ve sham grubundan daha düşüktü. Bu dönemde oositlerin çoğu MI fazında idi. Ayrıca ovariyan foliküllerde atretik değişiklikler oldukça fazla idi. Küçük çaplı foliküllerde oosite rastlanmazken, preantral foliküller normale yakın görünüme sahipti. Paralel şekilde radyasyon+süperovulasyon I grubunda da süperovulasyona yanıt oldukça zayıftı. Ovaryumlarda ovulasyon öncesi dönemde bloke olmuş foliküller gözlendi. Radyasyon II ve radyasyon+süperovulasyon II gruplarında, ovaryumda atretik değişikliklerin yanında foliküler kist benzeri yapılar gözlendi. Radyasyon uygulamasının ardından 16 denekten 8'inde östrus siklusu süresinin uzadığı gözlendi. Ancak, fazlara ait sitolojilerde değişiklik izlenmedi. Çalışmamızda, radyasyonun ovaryum morfolojisi, ovulasyon oranı ve oosit morfolojisi ve maturasyonu üzerine etkileri in vivo olarak ortaya konmuştur. Preantral ve antral aşamada radyasyona maruz kalan foliküllerin ovulasyon yeteneğinin azaldığı tespit edilmiştir. Radyasyonun ardından, siklus düzenli iken süpeovulasyona yanıtın zayıf olması, radyasyona bağlı olarak premature ovariyan yetmezliğin erken işareti kabul edilebilir. Anahtar kelimeler: radyasyon, ovulasyon oranı, ovaryum, östrus siklusuThe aim of our study was to show the effects of radiation on ovarium morphology, ovulation rate and estrus cycle by using morphologic and morphometric parameters. Only mice demonstrating at least 3 regular concecutive cycles and randomly divided into 7 goups. Spontaneous ovulation rates were obtained from Control, Radiation-Sham, Radiation-I and Radiation-II groups while superovulation rates were obtained from Superovulation, Radiation+Superovulation-I and Radiation+Superovulation-II groups. 7.2 Gy single dose and whole body radiation was appplied during the transition period from diestrus phase to proestrus phase. Oocytes were collected by exploding the ampulla region of mice in Radiation-I group, in the first ovulation period after radiation. Oocyte collection in Radiation-II group was done in the second ovulation period. In Radiation+Superovulation-I group, superovulation protocol was applied in the first proestrous phase and oocytes were collected after radiation. The same protocol was applied for Radiation+Superovulation-II group during the second proestrous phase. Ovaries of all groups were prepared for light microscopic observation. In the first ovulation period after the radiation, spontaneous ovulation rate and ovary weight were smaller than the control and the sham groups. Most of the oocytes were in MI phase during this period. Furthermore, atretic changes in ovarian follicles were quite dramatic. Preantral follicles had an appearance close to normal while no oocytes were found in small sized follicles. Similarly, response to superovulation was weak also in Radiation+Superovulation-I group. Follicles which blocked in pre-ovulatuary period were observed in the ovary. In radiation-II and Radiation+Superovulation-II groups, structures like follicular cyst?s were observed in addition to atretic changes in ovary. After radiation, longer estrus cycle periods were observed in 8 of 16 subjects. However, no changes in the cytologies of phases were detected. It was identified that in vivo effects of radiation even in early phases on ovarian morphology, ovulation rate, oocyte morphology and oocyte maturation in mice. Reduction in ovulation ability of follicles which are exposed to radiation during preantral and antral stages was determined. After radiation, low response to superovulation while the cycle is regular, can be accepted as an early sign of premature ovarian failure due to radiation. Keywords: radiation, ovulation rate, ovary, estrous cycle

The role of ionizing radiaton on ovulation rate and oocyte morphology in mouse

We investigated the effects of ionizing radiation on maturation ability and radiosensitivity of oocytes enclosed in preantral and antral follicles. Balb/c female mice received total body single dose gamma radiation (7.2 Gy) at the diestrous to proestrous transition period. In the first experiment, spontaneously ovulated oocytes were collected from irradiated animals. In the second experiment, irradiated animals were allowed to superovulate to assess the ovarian function. The spontaneous ovulation rate of the follicles exposed at antral stage was significantly lower than the sham-irradiated mice (p < 0.01), and most of the oocytes were found at the metaphase I stage. Oocyte morphology and the ovulation rate of the follicles exposed at preantral stage were similar to the sham-irradiated group. Minimal morphological abnormalities were observed in the oocytes and the polar body as well. The superovulation response of all the irradiated animals was lower than the respective control animals. The superovulation rate was significantly lower in the first ovulation after irradiation (p < 0.01). In conclusion, our findings indicate that total body gamma irradiation, on a basis of estrous cycle stages, leads to ovulation failure in the antral stage while causes abnormal oocyte morphology in the preantral stage follicles in mice

Effect of chronic physiological stress on rat oocyte reserve: Role of IGF-1, AMH and Bcl-2

393-402Ovarian activity has a complex physiology and is related to oocyte quality in women. This study investigates the effects of ovarian activity with chronic stress (CS) on behavioural parameters, estrous cycles, and ovarian follicular development in rats. Here, we examined the ovarian microenvironment against exposure to stress and to elucidate the stress-related ovarian molecular mechanisms. Twenty female Sprague-Dawley rats were divided into the control and the CS groups. The estrous cycle phases were detected by vaginal smear. Rats in the CS group were immobilized 1 h/day for 8 weeks. At the end of the experiment, all animals were subjected to behavioral tests in their metestrus phase and sacrificed on the other day (diestrus phase). The ovaries were harvested for histological analysis, blood samples were taken to measure cortisol levels. The immunoreactivities of ovarian IGF-1, AMH and Bcl-2 proteins were evaluated by immunohistochemistry. Here, we have studied CS-induced prolonged estrous cycles. We showed a lower number of developing follicles but the higher number of atretic follicles in the CS group’s ovaries. The dominant structure of ovarian histology was large interstitial glands. CS caused decreases in ovarian Bcl-2, IGF-1 and AMH immunoreactivities which have roles in follicular development. Also, anxiety was detected in CS-exposed animals. Our results showed that chronic restrainer stress can be a serious endocrine disrupter by reducing ovarian paracrine factors

Improving effect of voluntary exercise on high fructose diet induced kidney dysfunction and oxidant status in rats

Fruktoz tüketimindeki artışın oksidatif stresi artırarak böbrek fonksiyonlarını olumsuz etkilediği bilinmektedir. Egzersizin böbrek için koruyucu etkileri olduğu gösterilmiş olmasına karşın fruktozdan zengin beslenmeye bağlı değişimlerde istemli koşu egzersizinin etkileri bilinmemektedir. Çalışmamızda yüksek fruktozla beslenmenin böbrek fonksiyonu ve histolojisi üzerine meydana getirdiği olası etkiler ve oksidatif hasarda istemli fiziksel aktivitenin rolünü araştırdık. Deneyde kullanılan 21 adet erkek Sprague Dawley sıçan 3 gruba ayrıldı. Sekiz hafta süren deney boyunca Sedanter+su (kontrol) grubu içme suyu alırken sedanter+fruktozlu su (F) ve aktivite+fruktozlu su (A+F) grupları %20 fruktoz içeren içme suyu aldılar. A+F grubu 8 hafta boyunca dönen tekerlek bulunan kafes yardımıyla istemli fiziksel aktivite yaptı. Deney sonunda alınan kan örneklerinde üre ve kreatinin seviyeleri, böbrek dokularında malondialdehit ve glutatyon düzeyleri incelendi. Ayrıca böbrek dokusunun histopatolojik incelemesi yapıldı. Böbrek fonksiyonlarının göstergesi olan serum kreatinin seviyesi F grubunda kontrol grubuna göre yüksek bulundu (p=0,012). Malondialdehit (MDA) seviyesi F grubunda kontrol grubuna göre yüksek iken A+F grubunda kontrol grubuyla benzerdi (sırasıyla p=0,024 ve p>0,99). Glutatyon (GSH) seviyesi F ve A+F gruplarında kontrol grubuna göre yüksekti (sırasıyla p=0,015 ve p=0,001). GSH seviyesi A+F grubunda F grubuna göre anlamlı düzeyde yüksekti (p=0,014). Kontrol grubuna kıyasla F grubunun böbrek kesitlerinde glomerüler çap, glomeruloskleroz oranı ve kollajen yoğunluğunda artış görüldü. A+F grubunda kontrol grubuna benzer histolojik görünüm saptandı. Bu çalışma ile yüksek fruktozla beslenmeye bağlı böbrek yapısı ve fonksiyonlarında meydana gelen olumsuz etkilerin ve oksidatif hasarın istemli fiziksel aktivite ile önlenebileceği ortaya konmuştur.It is known that the increase in fructose consumption negatively affects kidney functions by increasing oxidative stress. Although exercise has been shown to have protective effects for the kidney, the effects of voluntary jogging exercise on changes due to fructose-rich diet are unknown. In our study, we investigated the possible effects of high fructose feeding on kidney function and histology and the role of volun tary physical activity in oxidative damage. The 21 male Sprague Dawley rats used in the experiment were divided into 3 groups. During the experiment, which lasted eight weeks, the sedentary + water (control) group received drinking water, while the sedentary + fructose water (F) and activity + fructose water (A + F) groups received drinking water containing 20% fructose. The A + F group performed voluntary physical activity for 8 weeks with the help of a cage with a rotating wheel. Urea and creatinine levels in blood samples taken at the end of the experiment, malondialdehyde and glutathione levels in kidney tissues were examined. In addition, histopathological examination of the kidney tissue was made. Serum creatinine level, which is an indicator of renal functions, was found to be higher in the F group compared to the control group (p = 0.012). While the malondialdehyde (MDA) level was higher in the F group compared to the control group, it was similar to the control group in the A + F group (p = 0.024 and p> 0.99, respectively). Glutathione (GSH) level was higher in F and A + F groups compared to the control group (p = 0.015 and p = 0.001, respectively). GSH level was significantly higher in the A + F group com pared to the F group (p = 0.014). Compared to the control group, an increase in glomerular diameter, glomerulosclerosis rate and collagen density were observed in the kidney sections of the F group. Histological appearance similar to the control group was detected in the A + F group. As a result of this study, it was revealed that the negative effects and oxidative damage on kidney structure and functions due to high fructose feeding can be prevented by voluntary physical activity

The Adriamycin Rat/Mouse Model And Its Importance To The Embryology

Adriyamisinin teratojenik etkisi ile oluşturulan sıçan ve fare modelleri; güvenilir, kolaylıkla uygulanabilen ve insanlarda VACTERL birlikteliğinde görülen anomalilere benzer oluşabilen bir dizi konjenital anomalinin embriyolojik ve moleküler biyolojik olarak araştırılmasına olanak veren modellerdir. Adriyamisinin VACTERL birlikteliğinde görülen konjenital anomalileri oluşturma mekanizması henüz tam olarak açıklanamamıştır. Bu modellerle yapılan araştırmalarda özellikle anormal notokord morfolojisi üzerinde durulmuş ve embriyo gelişiminde notokordun rolünün ve öneminin anlaşılmasına ışık tutmuştur. Ayrıca hatalı Sonic hedgehog (Shh) sinyal yolu da üzerinde durulan diğer mekanizmayı oluşturmaktadır. Bu derlemede, adriyamisin sıçan ve fare modelleri ile bu modellerin VACTERL birlikteliğinde görülen konjenital anomaliler üzerine etkisinin, güncel literatür bilgileri ışığında ele alınması amaçlanmıştır.Rat and mouse models induced by the teratogenic effect of adriamycin are reliable and easly reproducible methods of studying the embryology and molecular biology of a range of complex congenital anomalies similar to those seen in humans with VACTERL association. The mechanism by which adriamycin produces the congenital anomalies found in the VACTERL association is not yet clear. Studies with these models have focused on mainly abnormal notochord morphology, shedding more light on the important role of this structure in the developing embryo. Morover, defective Shh signaling pathway is another emphasized mechanism. This review aims to discuss adriamycin rat and mouse models and their impact on congenital anomalies similar to those seen in humans with VACTERL association, in the light of current literature data

Effect of fucoidan on PCNA, INSL3, JNK, TGF-β1, IL-1β and akt expressions in diabetic rat testicular tissues

Çalışmamızın amacı, diyabetik testis dokularında gözlenen hasarlarda etkili olabilme potansiyeli yüksek bir antioksidan olan fukoidanın, spermatogenez seri hücrelerine proliferasyon, apoptozis ve inflamasyon yönünden olası etkilerini araştırmaktır. Fukoidan; çeşitli amaçlarla tablet formunda tüketici kullanımına sunulmuş olmasına rağmen, diyabetli erkek hastalarda infertiliteye yönelik bir değerlendirme yapabilmek için yeterli veriler bulunmamaktadır. Bu amaçla, testis dokusunda prolifere hücre nükleer antijeni (PCNA), insulin-benzeri peptid 3 (INSL3), fosfo (f)-c-Jun N-terminal kinaz (f-JNK), dönüştürücü büyüme faktörü-β1 (TGF-β1), fosfo-serin/treonin protein kinaz (f-Akt) ve interlökin-1β (IL-1β) gibi biyobelirteçlerin ifadelerinin değerlendirilmesi planlanmıştır. Çalışmamızda yirmi dört adet Wistar albino erkek sıçan kullanılarak 4 deney grubu (n=6); K: Kontrol grubu, D: diyabet grubu; 40 mg/kg streptozotosin (STZ, 5 ardışık gün, intraperitoneal (i.p.) verilen grup, EF grubu: 40 mg/kg STZ i.p (5 ardışık gün) + 50 mg/kg i.p. fukoidan (Diyabet oluşumunun ertesi günü başlanarak 6 hafta süresince, günaşırı bir kez) verilen grup, GF grubu: 40 mg/kg STZ i.p. (5 ardışık gün) + 50 mg/kg i.p. fukoidan (diyabet oluşturulduktan 15 gün sonra, 6 hafta süresince günaşırı bir kez) verilen grup oluşturulmuştur. Diyabet indüksiyonuyla; immatur hücrelerde dökülme ve seminifer tübül duvarındaki hücrelerde izlenen sitoplazma kayıpları, belirgin dejeneratif değişiklikler olarak görülmüştür. Bununla birlikte diyabet, proliferasyon indeksinin yanısıra INSL3 ve f-Akt immunoreaktivitelerinde azalmaya; f-JNK, TGF-β1, IL-1β immunreaktivitelerinde ise artışa neden olmuştur. EF ve GF gruplarında ise çalışılan tüm parametrelerde, diyabetin etkilerini azaltma yönünde etki gözlenmiştir. Yaptığımız çalışma sonucunda, moleküler düzeyde etkili olabildiği önceki çalışmalarla da saptanan fukoidanın; diyabetik testis dokusundaki histopatolojik hasarlara karşı koruyucu etkileriyle, infertilite gibi üreme sağlığında oluşabilecek ciddi problemlerin önlenmesine katkı yapacağı kanısındayız.The aim of our study is to evaluate the possible effects of fucoidan, which is an antioxidant with high potential to be effective in histopathological damages in diabetic testicular tissue, on the proliferation, Leydig cell function, apoptosis and inflammation. For this purpose, we planned to evaluate protein expression of proliferated cell nuclear antigen (PCNA), insulin-like peptide 3 (INSL3) phospho-c-Jun N-terminal kinase (p-JNK), transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β) phospho-serine/threonine protein kinase (p-Akt) in testicular tissue. Although fucoidan has been presented to consumer use in tablet form for various purposes, there are insufficient data to make an assessment of infertility in male patients with diabetes. The animals were divided into four groups (n=6) using twenty-four Wistar albino male rats; K: control group, Group D: 40 mg/kg streptozotocin (STZ, 5 consecutive days, intraperitoneal (i.p.), EF group: 40 mg/kg STZ i.p (5 consecutive days)+50 mg/kg i.p. fucoidan (one time, every other day, during six weeks), GF group: 40 mg/kg STZ (5 consecutive days)+50 mg/kg i.p. fucoidan (after fifteen days induction diabetes, every other day, during six weeks). The shedding of immature cells and loss of the seminiferous tubule wall were seen as significant degenerative changes by diabetes induction. However diabetes decreased proliferation index, INSL3 and f-Akt immunoreactivity, whereas increased f-JNK, TGF-β1, IL-1β immunoreactivity. All parameters studied in EF and GF groups was observed reducing effects of diabetes. It was concluded that fucoidan may contribute to the prevention of some serious problems that may occur in male reproductive health, such as infertility

Preventive effect of doxycycline sponge against bisphosphonate-related osteonecrosis of the jaws: an animal study

The aim of this study is to investigate the effect of doxycycline collagen sponge on bisphosphonate-related osteonecrosis of the jaw (BRONJ) and the level of serum biomarkers as an indicator of osteonecrosis. Twenty-four rats were divided into four groups. Animals in the control group were injected with saline and animals in Groups I, II and III were injected with zoledronate three times a week for eight weeks. After eight weeks, the following procedures were performed in each group. In Group I: extraction of maxillary first molar, in Group II: extraction of maxillary first molar and mucoperiosteal coverage was performed and in Group III: extraction of maxillary first molar and mucoperiosteal coverage with doxycycline collagen sponges was performed. At the end of 16 weeks, all animals were sacrificed. Serum collagen type I C-telopeptide (CTx), tartrate-resistant acid phosphatase (TRACP 5b) and alkaline phosphatase (ALP) levels’ analysis, clinical examination, histological and histomorphometrical analysis were performed. As a result no significant difference in CTx, TRACP 5b and ALP levels was observed between groups. Complete mucosal healing was observed in all animals in the control group and 66.7% of animals in Group III. The necrotic bone area in Group III was significantly lower than the other groups (p < 0.01). Statistically significant difference was observed between groups in terms of detached osteoclast number (p < 0.01). In conclusion, local application of doxycycline could have a positive effect in reducing the risk of BRONJ in rats