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Histopathological evaluation of the effects of sildenafil on organ damage in a diabetic rat model

Year 2023, Volume: 6 Issue: 5, 1040 - 1046, 28.09.2023
https://doi.org/10.32322/jhsm.1347405

Abstract

Aims: In this study, it was aimed to show the effects of sildenafil on heart, liver and kidney tissues histopathologically by creating an experimental diabetes model with streptozocin.
Methods: Male adult Sprague dawley rat (48) was used in the study. The rats were first divided into three groups as control group, the diabetes group and the diabetes+sildenafil group. Each group was divided into two groups within itself. Streptozotocin 40 mg/kg was administered intraperitoneally to the rats in the groups that would develop diabetes and diabetes+sildenafil diabetes. Rats with blood glucose levels of 250 mg/dl and above after 48 hours were considered diabetic. Sildenafil citrate 10mg/kg/day was given by gavage to the diabetes+sildenafil group. At the end of the experiment heart, liver and kidney tissues were placed in formaldehyde solution. Hematoxylin-Eosin staining was applied to the sections taken. Histological changes in the stained sections were evaluated by a histologist. Histological evaluation was performed semi-quantitatively in heart, liver and kidney tissue. In the assessment, the findings of the tissues were scored and statistical analysis was performed.
Results: Histological findings of heart, liver and kidney tissues were examined. It was determined that less organ damage was seen in the diabetes+sildenafil group compared to the Diabetes group.
Conclusion: In our study, it has been demonstrated histologically that sildenafil can be a drug that has an antioxidant effect in tissue by helping to protect cell structure and architecture against heart, liver and kidney tissue damage caused by diabetes. It should not be overlooked that it is important to determine the appropriate dose and frequency of use of sildenafil in revealing these effects.

References

  • Hamamcıoglu AC. Diyabette oksidatif stres ve antioksidanların rolü. Turk J Diab Obes. 2017;1(1):7-13.
  • Ceriello A. Oxidative stress and glycemic regulation. Metabolism. 2000;49(2):27-29.
  • Bolat A, Gültekin Y. Investigation of the contribution of concentrated growth factor (CGF) and processed lipoaspirate (PLA) to wound healing in diabetic rats. J Health Sci Med. 2021;4(1):33-37.
  • Memişoğulları R. Diyabette serbest radikallerin rolü ve antioksidanların etkisi. Duzce Med J. 2005;7(3):30-39.
  • Hakseven M, Kapan M, Alabalık U, Avşar G. Sildenafil sitrat ve dekspantenolün yara iyileşmesi üzerindeki etkilerinin karşılaştırılması:deneysel çalışma. SDÜ Tıp Fakültesi Derg. 2022;29(3):368-377.
  • Berkowitz BA, Podolsky R, Lins Childers K, et al. Sildenafil-evoked photoreceptor oxidative stress in vivo is unrelated to impaired visual performance in mice. Plos One. 2021;16(3):e0245161.
  • Oudot A, Behr-Roussel D, Le Coz O et al. How does chronic sildenafil prevent vascular oxidative stress in insulin-resistant rats?. J Sex Med. 2010;7(1):79-88.
  • Sayın T, Özenci M. Sildenafilin primer pulmoner hipertansiyonda kalıcı uzun dönem yararlı etkisi. Ankara Üniversitesi Tıp Fakültesi Derg. 2006;59(1):23-25.
  • Laxmi V, Gupta R, Bhattacharya SK, Ray A, Gulati K. Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma. Pharmacol Rep. 2019;71(3):517-521.
  • Adıgüzel Ç, Kalender Y. Lead nitrate ınduced toxic effects on small ıntestine tissues in diabetic and non-diabetic rats:role of sodium selenite. Gazi University J Sci. 2015;28(4):541-544.
  • Karabulut D, Ulusoy HB, Kaymak E, Sönmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol. 2016;16(5):310-315.
  • Karabulut D, Ozturk E, Kaymak E, Akin AT, Yakan B. Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. J Biochem Mol Toxicol. 2021;35(1):e22618.
  • Akin AT, Öztürk E, Kaymak E, Karabulut D, Yakan B. Therapeutic effects of thymoquinone in doxorubicin-induced hepatotoxicity via oxidative stress, inflammation and apoptosis. Anat Histol Embryol. 2021;50(6):908-917.
  • Kara M, Baykan H, Karabulut D. Investigation of the effect of sildenafil on flap survival in a diabetic rat model. Ann Chir Plast Esthet. 2022;67(4):232-238.
  • Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel diyabet oluşturulan sıçanlarda kalp ve iskelet kası nrf2 yapımı ve oksidatif stres üzerine melatoninin etkisinin incelenmesi. Turk J Diab Obes. 2020;4(1):46-53.
  • Tuzcu Z, Gençoğlu H, Tuzcu M, Orhan C, Ağca CA, Şahin K. Diyabetik sıçanlarda taurinin kalp dokusu antioksidan düzeyleri ile nfκ-b ve nrf2 sinyal yolakları üzerine etkisi. FÜ Sağ Bil Vet Derg. 2018;32(2):105-110.
  • Giannattasio S, Corinaldesi C, Colletti M, et al. The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy:in vivo and in vitro evidence. J Endocrinol Invest. 2019;42(6):715-725.
  • Ebrahimi F, Shafaroodi H, Asadi S, et al. Sildenafil decreased cardiac cell apoptosis in diabetic mice:reduction of oxidative stress as a possible mechanism. J Physiol Pharmacol. 2009;87(7):556-564.
  • Yardimci S, Bostanci EB, Ozer I, et al. Sildenafil accelerates liver regeneration after partial hepatectomy in rats. Transplant Proc. 2012;44(6):1747-1750.
  • Şimşek T, Ersoy ÖF, Özsoy Z, et al. Effect of sildenafil citrate on the liver structure and function in obstructive jaundice:An experimental study. Turk J Surg. 2018;34(2):111-116.
  • El-Mahdy NA, El-Sayad ME, El-Kadem AH. Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model. Biomed Pharmacother. 2016;81:136-144.
  • Graziano S, Montana A, Zaami S et al. Sildenafil-associated hepatoxicity:a review of the literature. Eur Rev Med Pharmacol Sci. 2017;21(1):17-22.
  • Ala M, Mohammad Jafari R, Ala M, et al. Sildenafil improves radiation-induced oral mucositis by attenuating oxidative stress, NF-κB, ERK and JNK signalling pathways. J Cell Mol Med. 2022;26(16):4556-4565.
  • Hafez MH, El-Kazaz SE. The impact of phosphodiesterase-5 inhibitor (sildenafil citrate) on some hippocampal neurotransmitters, oxidative stress status, minerals, and anxiety-like behavior in rats. J Adv Vet Anim Res. 2020;7(2):281-289.
  • Jeong KH, Lee TW, Ihm CG, Lee SH, Moon JY, Lim SJ. Effects of sildenafil on oxidative and inflammatory injuries of the kidney in streptozotocin-induced diabetic rats. Am J Nephrol. 2009;29(3):274-282.
  • Jorge ARC, Marinho AD, Silveira JAM, et al. Phosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom. Toxicon. 2021;202:46-52.
Year 2023, Volume: 6 Issue: 5, 1040 - 1046, 28.09.2023
https://doi.org/10.32322/jhsm.1347405

Abstract

References

  • Hamamcıoglu AC. Diyabette oksidatif stres ve antioksidanların rolü. Turk J Diab Obes. 2017;1(1):7-13.
  • Ceriello A. Oxidative stress and glycemic regulation. Metabolism. 2000;49(2):27-29.
  • Bolat A, Gültekin Y. Investigation of the contribution of concentrated growth factor (CGF) and processed lipoaspirate (PLA) to wound healing in diabetic rats. J Health Sci Med. 2021;4(1):33-37.
  • Memişoğulları R. Diyabette serbest radikallerin rolü ve antioksidanların etkisi. Duzce Med J. 2005;7(3):30-39.
  • Hakseven M, Kapan M, Alabalık U, Avşar G. Sildenafil sitrat ve dekspantenolün yara iyileşmesi üzerindeki etkilerinin karşılaştırılması:deneysel çalışma. SDÜ Tıp Fakültesi Derg. 2022;29(3):368-377.
  • Berkowitz BA, Podolsky R, Lins Childers K, et al. Sildenafil-evoked photoreceptor oxidative stress in vivo is unrelated to impaired visual performance in mice. Plos One. 2021;16(3):e0245161.
  • Oudot A, Behr-Roussel D, Le Coz O et al. How does chronic sildenafil prevent vascular oxidative stress in insulin-resistant rats?. J Sex Med. 2010;7(1):79-88.
  • Sayın T, Özenci M. Sildenafilin primer pulmoner hipertansiyonda kalıcı uzun dönem yararlı etkisi. Ankara Üniversitesi Tıp Fakültesi Derg. 2006;59(1):23-25.
  • Laxmi V, Gupta R, Bhattacharya SK, Ray A, Gulati K. Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma. Pharmacol Rep. 2019;71(3):517-521.
  • Adıgüzel Ç, Kalender Y. Lead nitrate ınduced toxic effects on small ıntestine tissues in diabetic and non-diabetic rats:role of sodium selenite. Gazi University J Sci. 2015;28(4):541-544.
  • Karabulut D, Ulusoy HB, Kaymak E, Sönmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol. 2016;16(5):310-315.
  • Karabulut D, Ozturk E, Kaymak E, Akin AT, Yakan B. Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. J Biochem Mol Toxicol. 2021;35(1):e22618.
  • Akin AT, Öztürk E, Kaymak E, Karabulut D, Yakan B. Therapeutic effects of thymoquinone in doxorubicin-induced hepatotoxicity via oxidative stress, inflammation and apoptosis. Anat Histol Embryol. 2021;50(6):908-917.
  • Kara M, Baykan H, Karabulut D. Investigation of the effect of sildenafil on flap survival in a diabetic rat model. Ann Chir Plast Esthet. 2022;67(4):232-238.
  • Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel diyabet oluşturulan sıçanlarda kalp ve iskelet kası nrf2 yapımı ve oksidatif stres üzerine melatoninin etkisinin incelenmesi. Turk J Diab Obes. 2020;4(1):46-53.
  • Tuzcu Z, Gençoğlu H, Tuzcu M, Orhan C, Ağca CA, Şahin K. Diyabetik sıçanlarda taurinin kalp dokusu antioksidan düzeyleri ile nfκ-b ve nrf2 sinyal yolakları üzerine etkisi. FÜ Sağ Bil Vet Derg. 2018;32(2):105-110.
  • Giannattasio S, Corinaldesi C, Colletti M, et al. The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy:in vivo and in vitro evidence. J Endocrinol Invest. 2019;42(6):715-725.
  • Ebrahimi F, Shafaroodi H, Asadi S, et al. Sildenafil decreased cardiac cell apoptosis in diabetic mice:reduction of oxidative stress as a possible mechanism. J Physiol Pharmacol. 2009;87(7):556-564.
  • Yardimci S, Bostanci EB, Ozer I, et al. Sildenafil accelerates liver regeneration after partial hepatectomy in rats. Transplant Proc. 2012;44(6):1747-1750.
  • Şimşek T, Ersoy ÖF, Özsoy Z, et al. Effect of sildenafil citrate on the liver structure and function in obstructive jaundice:An experimental study. Turk J Surg. 2018;34(2):111-116.
  • El-Mahdy NA, El-Sayad ME, El-Kadem AH. Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model. Biomed Pharmacother. 2016;81:136-144.
  • Graziano S, Montana A, Zaami S et al. Sildenafil-associated hepatoxicity:a review of the literature. Eur Rev Med Pharmacol Sci. 2017;21(1):17-22.
  • Ala M, Mohammad Jafari R, Ala M, et al. Sildenafil improves radiation-induced oral mucositis by attenuating oxidative stress, NF-κB, ERK and JNK signalling pathways. J Cell Mol Med. 2022;26(16):4556-4565.
  • Hafez MH, El-Kazaz SE. The impact of phosphodiesterase-5 inhibitor (sildenafil citrate) on some hippocampal neurotransmitters, oxidative stress status, minerals, and anxiety-like behavior in rats. J Adv Vet Anim Res. 2020;7(2):281-289.
  • Jeong KH, Lee TW, Ihm CG, Lee SH, Moon JY, Lim SJ. Effects of sildenafil on oxidative and inflammatory injuries of the kidney in streptozotocin-induced diabetic rats. Am J Nephrol. 2009;29(3):274-282.
  • Jorge ARC, Marinho AD, Silveira JAM, et al. Phosphodiesterase-5 inhibitor sildenafil attenuates kidney injury induced by Bothrops alternatus snake venom. Toxicon. 2021;202:46-52.
There are 26 citations in total.

Details

Primary Language English
Subjects Medical Pharmacology
Journal Section Original Article
Authors

Mehmet Kara 0000-0003-0071-3740

Halit Baykan 0000-0002-3352-3946

Esra Önal 0000-0002-2631-6033

Ayşegül Burçin Yıldırım 0000-0002-2631-6033

Derya Karabulut 0000-0003-2067-6174

Early Pub Date September 26, 2023
Publication Date September 28, 2023
Published in Issue Year 2023 Volume: 6 Issue: 5

Cite

AMA Kara M, Baykan H, Önal E, Yıldırım AB, Karabulut D. Histopathological evaluation of the effects of sildenafil on organ damage in a diabetic rat model. J Health Sci Med / JHSM. September 2023;6(5):1040-1046. doi:10.32322/jhsm.1347405

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