Research Article
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Protective Effect of Cannabinoid Type 2 Receptor Agonist Against Ovarian Ischemia/reperfusion Injury in Rats

Year 2019, Volume: 9 Issue: 4, 679 - 686, 16.12.2019
https://doi.org/10.31832/smj.626204

Abstract

Objective: The aim of this study is to prove whether or not the cannabinoid
(CB)2 receptor agonist, which is known to be effective in
anti-inflammatory effects and tried in various organ and/or tissue ischemia/reperfusion
(I/R) injuries, works in the treatment of I/R injury, which is a replication of
the damage caused by clinical ovarian torsion.

Materials
and Methods:
Rats were divided
into five groups (n=6). After anesthesia, an approximately 2-cm incision was
made in the lower abdominal region of the rats and both ovaries, uterine horns,
and adnexa were occluded with a clamp for 30 min, except for the sham control group.
After 3 h, both ovaries were surgically removed. Blood was collected for the
measurement of cytokine levels in the serum.

Results:
The induction of ovaries by
I/R injury resulted in an increase in interleukin 1 beta, tumor necrosis factor
alpha, and malondialdehyde levels and decrease in glutathione (GSH) levels in
ovarian tissues and serum. The pretreatment of the CB2
receptor agonist decreased these cytokines levels in both ovarian tissues and
serum. The GSH level in both was reduced by I/R injury, while the agonist
increased the GSH level reduced by I/R injury. The administration of the
antagonist reversed the curative effect of the agonist.







Conclusion: The results of this study support that the CB2
receptor agonist can be used to treat I/R injury, which is an imitation of
ovarian torsion. However, no the clinical trial is a limitation of this study.

Supporting Institution

Adiyaman University

Project Number

TIPFYL/2019-0001

References

  • 1. Kurt RK, Dogan AC, Dogan M, et al. Protective effect of colchicine on ovarian ischemia-reperfusion injury: An experimental study. Reprod Sci. 2015;22(5):545-550. doi:10.1177/1933719114553065
  • 2. Kolusari A, Okyay AG, Koçkaya EA. The Effect of Erythropoietin in Preventing Ischemia–Reperfusion Injury in Ovarian Tissue Transplantation. Reprod Sci. 2018;25(3):406-413. doi:10.1177/1933719117715127
  • 3. Bayram S, Parlar A, Arslan SO. The curative effect of cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion. Fundam Clin Pharmacol. August 2019. doi:10.1111/fcp.12502
  • 4. Sayan H, Ozacmak VH, Altaner S, Aktas RG, Arslan SO. Protective Effects of L-Arginine on Rat Terminal Ileum Subjected to Ischemia/Reperfusion. J Pediatr Gastroenterol Nutr. 2008;46(1):29-35. doi:10.1097/01.mpg.0000304450.54057.96
  • 5. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell Biology of Ischemia/Reperfusion Injury. In: International Review of Cell and Molecular Biology. Vol 298. ; 2012:229-317. doi:10.1016/B978-0-12-394309-5.00006-7
  • 6. Esme H, Fidan H, Koken T, Solak O. Effect of lung ischemia–reperfusion on oxidative stress parameters of remote tissues. Eur J Cardio-Thoracic Surg. 2006;29(3):294-298. doi:10.1016/j.ejcts.2005.12.008
  • 7. Draper HH, Hadley M. [43] Malondialdehyde determination as index of lipid Peroxidation. In: Oxygen Radicals in Biological Systems Part B: Oxygen Radicals and Antioxidants. Vol 186. Methods in Enzymology. Academic Press; 1990:421-431. doi:https://doi.org/10.1016/0076-6879(90)86135-I
  • 8. Kumar V, Torben W, Mansfield J, et al. Cannabinoid Attenuation of Intestinal Inflammation in Chronic SIV-Infected Rhesus Macaques Involves T Cell Modulation and Differential Expression of Micro-RNAs and Pro-inflammatory Genes. Front Immunol. 2019;10:914. doi:10.3389/fimmu.2019.00914
  • 9. Bai J, Ge G, Wang Y, et al. A selective CB2 agonist protects against the inflammatory response and joint destruction in collagen-induced arthritis mice. Biomed Pharmacother. 2019;116. doi:10.1016/j.biopha.2019.109025
  • 10. Şahin Ç, Yıldırım N, Hortu İ, et al. Tadalafil attenuates ischaemic damage as well as reperfusion injury in the rat ovary. J Turkish Ger Gynecol Assoc. May 2019. doi:10.4274/jtgga.galenos.2019.2018.0121
  • 11. Sarac M, Bakal U, Kuloglu T, et al. Effects of Carnosine and Vitamin E on Nucleobindin 2 (NUCB2)/nesfatin-1, Ghrelin, Adropin, and Irisin in Experimentally Induced Ovarian Torsion. Ann Clin Lab Sci. 2018;48(3):345-354. http://www.ncbi.nlm.nih.gov/pubmed/29970439. Accessed September 1, 2019.
  • 12. Ozlem K, Birkan Y, Mustafa K, Emin K. Protective effect of Vaccinium myrtillus on ischemia- reperfusion injury in rat ovary. Taiwan J Obstet Gynecol. 2018;57(6):836-841. doi:10.1016/j.tjog.2018.10.012
  • 13. Yildirim N, Simsek D, Kose S, et al. The protective effect of Gingko biloba in a rat model of ovarian ischemia/reperfusion injury: Improvement in histological and biochemical parameters. Adv Clin Exp Med. 2018;27(5):591-597. doi:10.17219/acem/68896
  • 14. Eser A, Hizli D, Haltas H, et al. Effects of curcumin on ovarian ischemia-reperfusion injury in a rat model. Biomed Reports. 2015;3(6):807-813. doi:10.3892/br.2015.515
  • 15. Celik Kavak E, Gulcu Bulmus F, Bulmus O, Kavak SB, Kocaman N. Magnesium: does it reduce ischemia/reperfusion injury in an adnexal torsion rat model? Drug Des Devel Ther. 2018;Volume 12:409-415. doi:10.2147/DDDT.S157115
  • 16. Woerly G, Honda K, Loyens M, et al. Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation. J Exp Med. 2003;198(3):411-421. doi:10.1084/JEM.20021384
  • 17. Marefati N, Eftekhar N, Kaveh M, Boskabadi J, Beheshti F, Boskabady MH. The Effect of <b><i>Allium cepa</i></b> Extract on Lung Oxidant, Antioxidant, and Immunological Biomarkers in Ovalbumin-Sensitized Rats. Med Princ Pract. 2018;27(2):122-128. doi:10.1159/000487885
  • 18. Parlar A, Arslan SO, Doğan MF, et al. The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress. Exp Ther Med. 2018;16(6):4900-4908. doi:10.3892/etm.2018.6753
  • 19. Parlar A, Arslan SO. Thymoquinone exhibits anti-inflammatory, antioxidant, and immunomodulatory effects on allergic airway inflammation. Arch Clin Exp Med. 2019;4(2):60-65. doi:10.25000/acem.527359
  • 20. Kopko J, Stańczak R, Warzecha D, Wielgos M. Uterine torsion in the second trimester of pregnancy. Neuro Endocrinol Lett. 2019;39(6):423-426. http://www.ncbi.nlm.nih.gov/pubmed/30796791. Accessed August 27, 2019.
  • 21. Halici Z, Karaca M, Keles ON, et al. Protective effects of amlodipine on ischemia-reperfusion injury of rat ovary: biochemical and histopathologic evaluation. Fertil Steril. 2008;90(6):2408-2415. doi:10.1016/j.fertnstert.2007.10.007
  • 22. Saat N, Risvanli A, Dogan H, et al. Effect of melatonin on torsion and reperfusion induced pathogenesis of rat uterus. Biotech Histochem. 2019. doi:10.1080/10520295.2019.1605456
  • 23. Namdar D, Koltai H. Medical Cannabis for the Treatment of Inflammation. Nat Prod Commun. 2018;13(3):1934578X1801300. doi:10.1177/1934578X1801300304
  • 24. Parlar A, Arslan SO. Resveratrol normalizes the deterioration of smooth muscle contractility following intestinal ischemia and reperfusion in rats associated with an anti-oxidative effect and modulating TNF-α activity. Ann Vasc Surg. August 2019. doi:10.1016/j.avsg.2019.06.027
  • 25. Frisher M, White S, Varbiro G, et al. The role of cannabis and cannabinoids in diabetes. Br J Diabetes Vasc Dis. 2010;10(6):267-273. doi:10.1177/1474651410385860
  • 26. Eken MK, Ersoy GS, Kaygusuz EI, et al. Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model. Arch Med Sci. 2019;15(4):1104-1112. doi:10.5114/aoms.2017.72406
  • 27. Gordeeva AE, Sharapov MG, Tikhonova I V., et al. Vascular Pathology of Ischemia/Reperfusion Injury of Rat Small Intestine. Cells Tissues Organs. 2017;203(6):353-364. doi:10.1159/000455830
  • 28. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78(3):206-209. doi:10.1111/1523-1747.ep12506462
  • 29. Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 1986;123(3):520-531. http://www.ncbi.nlm.nih.gov/pubmed/3717304. Accessed August 28, 2019.
  • 30. Noori Hassanvand M, Soleimani Mehranjani M, Shojafar E. Melatonin improves the structure and function of autografted mice ovaries through reducing inflammation: A stereological and biochemical analysis. Int Immunopharmacol. 2019;74:105679. doi:10.1016/j.intimp.2019.105679
  • 31. Turcotte C, Blanchet M-R, Laviolette M, Flamand N. The CB2 receptor and its role as a regulator of inflammation. Cell Mol Life Sci. 2016;73(23):4449-4470. doi:10.1007/s00018-016-2300-4
  • 32. Klein TW, Lane B, Newton CA, Friedman H. The Cannabinoid System and Cytokine Network (44546): https://doi.org/101177/153537020022500101. November 2016. doi:10.1177/153537020022500101
  • 33. Zhang Q, Bu S, Sun J, et al. Paracrine effects of human amniotic epithelial cells protect against chemotherapy-induced ovarian damage. Stem Cell Res Ther. 2017;8(1):270. doi:10.1186/s13287-017-0721-0
  • 34. Robinson ES, Alves P, Bashir MM, Zeidi M, Feng R, Werth VP. Cannabinoid Reduces Inflammatory Cytokines, Tumor Necrosis Factor-α, and Type I Interferons in Dermatomyositis In Vitro. J Invest Dermatol. 2017;137(11):2445-2447. doi:10.1016/j.jid.2017.05.035
  • 35. Zhu M, Yu B, Bai J, et al. Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis. J Bone Miner Res. 2019;34(4):739-751. doi:10.1002/jbmr.3637

Kannabinoid Tip 2 Reseptör Agonistinin Sıçanlarda Over İskemi/reperfüzyon Hasarına Karşı Koruyucu Etkisi

Year 2019, Volume: 9 Issue: 4, 679 - 686, 16.12.2019
https://doi.org/10.31832/smj.626204

Abstract

Amaç: Bu çalışmanın amacı, anti-enflamatuar etkili olduğu
bilinen ve çeşitli organ ve / veya doku iskemisi / reperfüzyon (I / R)
yaralanmalarında denenen kannabinoid (CB) 2 reseptör agonistinin klinik over
torsiyonunun neden olduğu hasarın bir kopyası olan I / R hasarının tedavisinde
etkisinin olup olmadığını kanıtlamaktır.



Gereç
ve yöntemler:
Ratlar
beş gruba ayrıldı (n = 6). Anestezi sonrası, sıçanların alt karın bölgesinde
yaklaşık 2 cm'lik bir insizyon yapıldı ve her iki yumurtalık, rahim boynuzu ve
adneks, şam kontrol grubu hariç 30 dakika boyunca bir klemp ile kapatıldı. 3
saat sonra, her iki yumurtalık cerrahi olarak çıkarıldı. Serumdaki sitokin
seviyelerinin ölçümü için kan alındı.



Bulgular: Yumurtalıkların I / R hasarı ile indüklenmesi,
interlökin 1 beta (IL-1β), tümör nekroz faktörü alfa (TNF-α) ve malondialdehit
(MDA) seviyelerinde bir artışa ve yumurtalık dokularında ve serumda glutatyon
(GSH) seviyelerinde bir azalmaya neden olmuştur. CB2 reseptörü agonistinin ön
tedavisi, hem over dokularında hem de serumda bu sitokin seviyelerini
düşürmüştür. Her ikisindeki GSH seviyesi I / R hasarı ile azalırken, agonist I
/ R hasarı tarafından azaltılmış GSH seviyesini arttırmıştır. Antagonistin
verilmesi, agonistin iyileştirici etkisini tersine çevirdi.



Sonuç: Bu çalışmanın sonuçları CB2 reseptörü agonistinin,
yumurtalık torsiyonunun bir taklidi olan I / R hasarını tedavi etmek için
kullanılabileceğini desteklemektedir. Ancak, klinik çalışma yapılmaması bu
çalışmanın bir sınırlamasıdır.

Project Number

TIPFYL/2019-0001

References

  • 1. Kurt RK, Dogan AC, Dogan M, et al. Protective effect of colchicine on ovarian ischemia-reperfusion injury: An experimental study. Reprod Sci. 2015;22(5):545-550. doi:10.1177/1933719114553065
  • 2. Kolusari A, Okyay AG, Koçkaya EA. The Effect of Erythropoietin in Preventing Ischemia–Reperfusion Injury in Ovarian Tissue Transplantation. Reprod Sci. 2018;25(3):406-413. doi:10.1177/1933719117715127
  • 3. Bayram S, Parlar A, Arslan SO. The curative effect of cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion. Fundam Clin Pharmacol. August 2019. doi:10.1111/fcp.12502
  • 4. Sayan H, Ozacmak VH, Altaner S, Aktas RG, Arslan SO. Protective Effects of L-Arginine on Rat Terminal Ileum Subjected to Ischemia/Reperfusion. J Pediatr Gastroenterol Nutr. 2008;46(1):29-35. doi:10.1097/01.mpg.0000304450.54057.96
  • 5. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell Biology of Ischemia/Reperfusion Injury. In: International Review of Cell and Molecular Biology. Vol 298. ; 2012:229-317. doi:10.1016/B978-0-12-394309-5.00006-7
  • 6. Esme H, Fidan H, Koken T, Solak O. Effect of lung ischemia–reperfusion on oxidative stress parameters of remote tissues. Eur J Cardio-Thoracic Surg. 2006;29(3):294-298. doi:10.1016/j.ejcts.2005.12.008
  • 7. Draper HH, Hadley M. [43] Malondialdehyde determination as index of lipid Peroxidation. In: Oxygen Radicals in Biological Systems Part B: Oxygen Radicals and Antioxidants. Vol 186. Methods in Enzymology. Academic Press; 1990:421-431. doi:https://doi.org/10.1016/0076-6879(90)86135-I
  • 8. Kumar V, Torben W, Mansfield J, et al. Cannabinoid Attenuation of Intestinal Inflammation in Chronic SIV-Infected Rhesus Macaques Involves T Cell Modulation and Differential Expression of Micro-RNAs and Pro-inflammatory Genes. Front Immunol. 2019;10:914. doi:10.3389/fimmu.2019.00914
  • 9. Bai J, Ge G, Wang Y, et al. A selective CB2 agonist protects against the inflammatory response and joint destruction in collagen-induced arthritis mice. Biomed Pharmacother. 2019;116. doi:10.1016/j.biopha.2019.109025
  • 10. Şahin Ç, Yıldırım N, Hortu İ, et al. Tadalafil attenuates ischaemic damage as well as reperfusion injury in the rat ovary. J Turkish Ger Gynecol Assoc. May 2019. doi:10.4274/jtgga.galenos.2019.2018.0121
  • 11. Sarac M, Bakal U, Kuloglu T, et al. Effects of Carnosine and Vitamin E on Nucleobindin 2 (NUCB2)/nesfatin-1, Ghrelin, Adropin, and Irisin in Experimentally Induced Ovarian Torsion. Ann Clin Lab Sci. 2018;48(3):345-354. http://www.ncbi.nlm.nih.gov/pubmed/29970439. Accessed September 1, 2019.
  • 12. Ozlem K, Birkan Y, Mustafa K, Emin K. Protective effect of Vaccinium myrtillus on ischemia- reperfusion injury in rat ovary. Taiwan J Obstet Gynecol. 2018;57(6):836-841. doi:10.1016/j.tjog.2018.10.012
  • 13. Yildirim N, Simsek D, Kose S, et al. The protective effect of Gingko biloba in a rat model of ovarian ischemia/reperfusion injury: Improvement in histological and biochemical parameters. Adv Clin Exp Med. 2018;27(5):591-597. doi:10.17219/acem/68896
  • 14. Eser A, Hizli D, Haltas H, et al. Effects of curcumin on ovarian ischemia-reperfusion injury in a rat model. Biomed Reports. 2015;3(6):807-813. doi:10.3892/br.2015.515
  • 15. Celik Kavak E, Gulcu Bulmus F, Bulmus O, Kavak SB, Kocaman N. Magnesium: does it reduce ischemia/reperfusion injury in an adnexal torsion rat model? Drug Des Devel Ther. 2018;Volume 12:409-415. doi:10.2147/DDDT.S157115
  • 16. Woerly G, Honda K, Loyens M, et al. Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation. J Exp Med. 2003;198(3):411-421. doi:10.1084/JEM.20021384
  • 17. Marefati N, Eftekhar N, Kaveh M, Boskabadi J, Beheshti F, Boskabady MH. The Effect of <b><i>Allium cepa</i></b> Extract on Lung Oxidant, Antioxidant, and Immunological Biomarkers in Ovalbumin-Sensitized Rats. Med Princ Pract. 2018;27(2):122-128. doi:10.1159/000487885
  • 18. Parlar A, Arslan SO, Doğan MF, et al. The exogenous administration of CB2 specific agonist, GW405833, inhibits inflammation by reducing cytokine production and oxidative stress. Exp Ther Med. 2018;16(6):4900-4908. doi:10.3892/etm.2018.6753
  • 19. Parlar A, Arslan SO. Thymoquinone exhibits anti-inflammatory, antioxidant, and immunomodulatory effects on allergic airway inflammation. Arch Clin Exp Med. 2019;4(2):60-65. doi:10.25000/acem.527359
  • 20. Kopko J, Stańczak R, Warzecha D, Wielgos M. Uterine torsion in the second trimester of pregnancy. Neuro Endocrinol Lett. 2019;39(6):423-426. http://www.ncbi.nlm.nih.gov/pubmed/30796791. Accessed August 27, 2019.
  • 21. Halici Z, Karaca M, Keles ON, et al. Protective effects of amlodipine on ischemia-reperfusion injury of rat ovary: biochemical and histopathologic evaluation. Fertil Steril. 2008;90(6):2408-2415. doi:10.1016/j.fertnstert.2007.10.007
  • 22. Saat N, Risvanli A, Dogan H, et al. Effect of melatonin on torsion and reperfusion induced pathogenesis of rat uterus. Biotech Histochem. 2019. doi:10.1080/10520295.2019.1605456
  • 23. Namdar D, Koltai H. Medical Cannabis for the Treatment of Inflammation. Nat Prod Commun. 2018;13(3):1934578X1801300. doi:10.1177/1934578X1801300304
  • 24. Parlar A, Arslan SO. Resveratrol normalizes the deterioration of smooth muscle contractility following intestinal ischemia and reperfusion in rats associated with an anti-oxidative effect and modulating TNF-α activity. Ann Vasc Surg. August 2019. doi:10.1016/j.avsg.2019.06.027
  • 25. Frisher M, White S, Varbiro G, et al. The role of cannabis and cannabinoids in diabetes. Br J Diabetes Vasc Dis. 2010;10(6):267-273. doi:10.1177/1474651410385860
  • 26. Eken MK, Ersoy GS, Kaygusuz EI, et al. Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model. Arch Med Sci. 2019;15(4):1104-1112. doi:10.5114/aoms.2017.72406
  • 27. Gordeeva AE, Sharapov MG, Tikhonova I V., et al. Vascular Pathology of Ischemia/Reperfusion Injury of Rat Small Intestine. Cells Tissues Organs. 2017;203(6):353-364. doi:10.1159/000455830
  • 28. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982;78(3):206-209. doi:10.1111/1523-1747.ep12506462
  • 29. Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 1986;123(3):520-531. http://www.ncbi.nlm.nih.gov/pubmed/3717304. Accessed August 28, 2019.
  • 30. Noori Hassanvand M, Soleimani Mehranjani M, Shojafar E. Melatonin improves the structure and function of autografted mice ovaries through reducing inflammation: A stereological and biochemical analysis. Int Immunopharmacol. 2019;74:105679. doi:10.1016/j.intimp.2019.105679
  • 31. Turcotte C, Blanchet M-R, Laviolette M, Flamand N. The CB2 receptor and its role as a regulator of inflammation. Cell Mol Life Sci. 2016;73(23):4449-4470. doi:10.1007/s00018-016-2300-4
  • 32. Klein TW, Lane B, Newton CA, Friedman H. The Cannabinoid System and Cytokine Network (44546): https://doi.org/101177/153537020022500101. November 2016. doi:10.1177/153537020022500101
  • 33. Zhang Q, Bu S, Sun J, et al. Paracrine effects of human amniotic epithelial cells protect against chemotherapy-induced ovarian damage. Stem Cell Res Ther. 2017;8(1):270. doi:10.1186/s13287-017-0721-0
  • 34. Robinson ES, Alves P, Bashir MM, Zeidi M, Feng R, Werth VP. Cannabinoid Reduces Inflammatory Cytokines, Tumor Necrosis Factor-α, and Type I Interferons in Dermatomyositis In Vitro. J Invest Dermatol. 2017;137(11):2445-2447. doi:10.1016/j.jid.2017.05.035
  • 35. Zhu M, Yu B, Bai J, et al. Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis. J Bone Miner Res. 2019;34(4):739-751. doi:10.1002/jbmr.3637
There are 35 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Buket Bilgin Şahin This is me 0000-0002-1106-6641

Ali Parlar 0000-0002-4656-3402

Project Number TIPFYL/2019-0001
Publication Date December 16, 2019
Submission Date September 28, 2019
Published in Issue Year 2019 Volume: 9 Issue: 4

Cite

AMA Bilgin Şahin B, Parlar A. Protective Effect of Cannabinoid Type 2 Receptor Agonist Against Ovarian Ischemia/reperfusion Injury in Rats. Sakarya Tıp Dergisi. December 2019;9(4):679-686. doi:10.31832/smj.626204

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