The effect of melatonin in rats with uterine torsion on uterus contractions, and the levels of ADMA, SDMA, arginine, Hsp90, TLR4, and NF-κB
Abstract
In this study was aimed at reducing uterine damage and increasing fertility after uterine torsion in pregnant animals. With this aim, uterine torsion was experimentally formed in 35 rats that were between 18-19 days pregnant. The animals were randomly divided into five groups, and melatonin was administered prior to torsion, at the time of torsion, and detorsion (10 mg/kg/gün IP). Ovario-hysterectomy operation was performed on all animals on the first day following parturition. Subsequently, from the obtained uterus samples, determination of the levels of asymmetrical dimethyl arginin (ADMA), symmetrical dimethyl arginin (SDMA), and arginine was made using the high-performance liquid chromatography (HPLC) and levels of Heat shock protein 90 (Hsp90), TLR4 (Toll Like Receptor 4) and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were measured using the Western blot technique. The contraction-relaxation responses of the myometrium were also determined in the organ baths. According to the results of the western blot, higher protein expressions than those of the control group were determined in the second, third, fourth, and fifth groups in Hsp90, TLR4, NF-κB. The lowest values of arginine and ADMA were found in Group 3, whilst the lowest SDMA value was determined in Group 1. It was determined that melatonin reduces tissue damage secondary to torsio uteri and, furthermore, that administration of this hormone at the time of torsion formation was more effective than its administration at the time of detorsion.
References
- Abd-Allah AR, El-Sayed ESM, Abdel-Wahab MH, et al. (2003): Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats. Pharmacol Res, 47, 349-354.
- Ayar A, Kutlu S, Yilmaz B, et al. (2001): Melatonin inhibits spontaneous and oxytocin-induced contractions of rat myometrium in vitro. Neuroendocrinol Lett, 22, 199-207.
- Bakan V, Çıralık H, Tolun F (2009): Protective effect of erythropoietin on torsion/detorsion injury in rat model. J Pediatr Surg, 44, 1988–1994.
- Breen AP, Murphy JA (1995): Reactions of oxyl radicals with DNA. Free Radic Biol Med, 18, 1033–1037.
- Ferrigno A, Rizzo V, Bianchi A, et al. (2014): Changes in ADMA/DDAH pathway after hepatic ischemia/reperfusion injury in rats: the role of bile. BioMed Res Int, Article ID 627434.
- Ha T, Liu L, Kelley J (2011): Toll-like receptors: new players in myocardial ischemia/reperfusion injury. Antioxid Redox Signal, 15, 1875-1893.
- Halici Z, Karaca M, Keles ON, et al. 2008. Protective effects of amlodipine on ischemia–reperfusion injury of rat ovary: biochemical and histopathologic evaluation. Fertil Steril, 90, 2408–2415.
- Herrmann O, Baumann B, de Lorenzi R, et al. (2005): IKK mediates ischemia-induced neuronal death. Nat Med, 11, 1322-1329.
- Kilic E, Ozdemir YG, Bolay H, et al. (1999): Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia. J Cereb Blood Flow Metab, 19, 511-516.
- Lyons NA, Knight JTJD, Aldridge BM, et al. (2013): Incidence, management and outcomes of uterine torsion in dairy cows. Cattle Pract, 21:1-6.
- Musal B, Köker A. (2015): Dystocia. 195-257. In: (Semacan A, Kaymaz M, Findik M, Risvanli A, Koker A. (eds), Obstetrics and Gynecology in Farm Animals, 1st ed. Medipres, Malatya, Turkey.
- Risvanli A, Aydin M, Kaygusuzoglu E, et al. (2003): The effect of thyroidectomy on sexual cycle and pregnancy rates in rats. Turkish J Vet Anim Sci, 27, 873-877. Sewerynek E, Reiter RJ, Melchorri D, et al. (1996): Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin. Hepatogastroenterol, 43, 898-905.
- Shimizu H, Saito, S, Higashiyama Y, et al. (2013): CREB, NF-kappaB, and NADPH oxidase coordinately upregulate indoxyl sulfate induced angiotensinogen expression in proximal tubular cells. Am J Physiol Cell Physiol, 304, 685-692.
- Taskin O, Birincioglu M, Aydin A, et al. (1998): The effects of twisted ischemic adnexa managed by detorsion on ovarian viability and histology: an ischemia-reperfusion rodent model. Hum Reprod, 13, 2823-2827. Teerlink T, Nijveldt RJ, De Jong S, et al. (2002): Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem, 303, 131-137.
- Turkoz Y, Celik O, Hascalik S, et al. (2004): Melatonin reduces torsion–detorsion injury in rat ovary: biochemical and histopathologic evaluation. J Pineal Res 37, 137–141.
- Yagnik GP, Takahashi Y, Tsoulfas G, et al. (2002): Blockade of the L-arginine/NO synthase pathway worsens hepatic apoptosis and liver transplant preservation injury. Hepatol, 36, 573–581.
Torsiyo uterili ratlarda melatoninin uterus kontraksiyonları, ADMA, SDMA, arjinin, Hsp90, TLR4 ve NFκB düzeylerine etkisi
Abstract
Bu çalışmada gebe hayvanlarda torsiyo uteri sonrası şekillenen uterus hasarını azaltmaya ve fertiliteyi artırmaya yönelik bir çalışma planlandı. Bu amaçla 35 adet 18-19 günlük gebe ratda deneysel olarak torsiyo uteri oluşturuldu. Hayvanlar rastgele 5 gruba ayrılarak torsiyon öncesi, torsiyon anında ve detorsiyon sırasında melatonin (10 mg/kg/gün IP) uygulandı. Doğum sonrası ilk gün tüm hayvanlara ovariohisterektomi operasyonu yapılarak kornulardan numuneler alındı. Daha sonra elde edilen uterus dokularında asymmetrical dimethyl arginin (ADMA), symmetrical dimethyl arginin (SDMA) ve Arjinin miktar tayinleri yüksek performanslı sıvı kromatografisi (HPLC) ve Heat shock protein 90 (Hsp90), TLR4 (Toll Like Receptor 4) ve NFκB (Nuclear factor kappa-light-chainenhancer of activated B cells) düzeyleri ise Western Blot ile belirlendi. Miyometriyumun in vitro kasılma gevşeme cevapları da organ banyosunda tespit edildi. Western blot sonuçlarına göre HSP90, TLR4, NFκB’da 2, 3, 4 ve 5. gruplarda kontrol grubuna göre daha fazla protein ekspresyonu olduğu belirlendi. Arjinin ve ADMA değerleri en düşük olarak 3. grupta bulundu. En düşük SDMA değeri ise 1. grupta tespit edildi. Sonuç olarak; elde edilen tüm bu veriler melatoninin torsiyo uteriye bağlı doku hasarını azalttığı ayrıca bu hormonun torsiyonun şekillendiği anda uygulanmasının detorsiyon anında uygulanmasına göre daha etkili olduğu kanaatine varıldı.
Keywords
References
- Abd-Allah AR, El-Sayed ESM, Abdel-Wahab MH, et al. (2003): Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats. Pharmacol Res, 47, 349-354.
- Ayar A, Kutlu S, Yilmaz B, et al. (2001): Melatonin inhibits spontaneous and oxytocin-induced contractions of rat myometrium in vitro. Neuroendocrinol Lett, 22, 199-207.
- Bakan V, Çıralık H, Tolun F (2009): Protective effect of erythropoietin on torsion/detorsion injury in rat model. J Pediatr Surg, 44, 1988–1994.
- Breen AP, Murphy JA (1995): Reactions of oxyl radicals with DNA. Free Radic Biol Med, 18, 1033–1037.
- Ferrigno A, Rizzo V, Bianchi A, et al. (2014): Changes in ADMA/DDAH pathway after hepatic ischemia/reperfusion injury in rats: the role of bile. BioMed Res Int, Article ID 627434.
- Ha T, Liu L, Kelley J (2011): Toll-like receptors: new players in myocardial ischemia/reperfusion injury. Antioxid Redox Signal, 15, 1875-1893.
- Halici Z, Karaca M, Keles ON, et al. 2008. Protective effects of amlodipine on ischemia–reperfusion injury of rat ovary: biochemical and histopathologic evaluation. Fertil Steril, 90, 2408–2415.
- Herrmann O, Baumann B, de Lorenzi R, et al. (2005): IKK mediates ischemia-induced neuronal death. Nat Med, 11, 1322-1329.
- Kilic E, Ozdemir YG, Bolay H, et al. (1999): Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia. J Cereb Blood Flow Metab, 19, 511-516.
- Lyons NA, Knight JTJD, Aldridge BM, et al. (2013): Incidence, management and outcomes of uterine torsion in dairy cows. Cattle Pract, 21:1-6.
- Musal B, Köker A. (2015): Dystocia. 195-257. In: (Semacan A, Kaymaz M, Findik M, Risvanli A, Koker A. (eds), Obstetrics and Gynecology in Farm Animals, 1st ed. Medipres, Malatya, Turkey.
- Risvanli A, Aydin M, Kaygusuzoglu E, et al. (2003): The effect of thyroidectomy on sexual cycle and pregnancy rates in rats. Turkish J Vet Anim Sci, 27, 873-877. Sewerynek E, Reiter RJ, Melchorri D, et al. (1996): Oxidative damage in the liver induced by ischemia-reperfusion: protection by melatonin. Hepatogastroenterol, 43, 898-905.
- Shimizu H, Saito, S, Higashiyama Y, et al. (2013): CREB, NF-kappaB, and NADPH oxidase coordinately upregulate indoxyl sulfate induced angiotensinogen expression in proximal tubular cells. Am J Physiol Cell Physiol, 304, 685-692.
- Taskin O, Birincioglu M, Aydin A, et al. (1998): The effects of twisted ischemic adnexa managed by detorsion on ovarian viability and histology: an ischemia-reperfusion rodent model. Hum Reprod, 13, 2823-2827. Teerlink T, Nijveldt RJ, De Jong S, et al. (2002): Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem, 303, 131-137.
- Turkoz Y, Celik O, Hascalik S, et al. (2004): Melatonin reduces torsion–detorsion injury in rat ovary: biochemical and histopathologic evaluation. J Pineal Res 37, 137–141.
- Yagnik GP, Takahashi Y, Tsoulfas G, et al. (2002): Blockade of the L-arginine/NO synthase pathway worsens hepatic apoptosis and liver transplant preservation injury. Hepatol, 36, 573–581.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Surgery |
| Journal Section | Research Article |
| Authors | |
| Publication Date | June 14, 2019 |
| Published in Issue | Year 2019Volume: 66 Issue: 3 |