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Hiperglisemik Sıçanların Karaciğerindeki Oksidatif Stres ve Histopatolojik Değişikliklerin Araştırılması

Yıl 2025, Cilt: 14 Sayı: 1, 101 - 106, 28.03.2025

Öz

Amaç: Bu çalışmada sıçanlarda hipergliseminin karaciğer üzerine etkisinin değerlendirilmesi amaçlandı. Gereç ve Yöntem: Sprague-Dawley tipi sıçanlarda, streptozotosin ile deneysel diyabet modeli oluşturuldu ve kan glikozunun 250 dl/kg'nin üzerinde olduğu sıçanlar diyabetik kabul edildi. 6 hafta süren deney boyunca, haftalık olarak kan glikozu ve ağırlık takibi yapıldı. Sakrifikasyondan sonra alınan karaciğer dokuları, histolojik incelemeler için formaldehit ile fikse edildi ve doku takibinin ardından parafine gömülmüştür. Parafin bloklardan alınan 4 um'lik kesitlerde hematoksilen ve eozin boyaması yapıldı ve kesitler histopatolojik olarak değerlendirildi. Aynı zamanda bu kesitlerde aktif kazpaz-3 işaretlemesi ile apoptoz, immünohistokimyasal olarak incelendi. Son olarak karaciğer dokusundaki oksidatif stres durumu, hidrojen peroksit (H2O2) ve süperoksit dismutaz (SOD) seviyeleri üzerinden analiz edildi. Bulgular: Sonuçlara göre, hiperglisemi grubundaki sıçanlara ait karaciğerlerde H2O2 düzeyinin anlamlı derecede yükseldiği ve SOD düzeyinin bir miktar düştüğü, hepatositlerde apoptoza giden hücre sayısının arttığı görüldü. Karaciğer histopatolojisi, hiperglisemi grubunda bozulmuş karaciğer lobüler yapısını, santral ven ve sinusoidal dilatasyonları, hepatositlerde küçülmeyi ve lenfositik infiltrasyonu ortaya koydu. Sonuç: Bu çalışma, diyabet kaynaklı karaciğer fonksiyon bozukluğunda oksidatif stres ve apoptozun kritik rolünü vurgulayarak, hiperglisemi kaynaklı karaciğer hasarına karşı koruma sağlamak ve diyabetli hastalarda sonuçları iyileştirmek için yeni tedavi stratejilerine olan ihtiyacı vurgulamaktadır.

Kaynakça

  • Adu, M. D., Malabu, U. H., Malau-Aduli, A. E. O., & Malau-Aduli, B. S. (2019). Enablers and barriers to effective diabetes self-management: A multi-national investigation. PLoS ONE, 14(6), e0217771. https://doi.org/10.1371/journal.pone.0217771
  • Al-Shaeli, S. J. J., Ethaeb, A. M., & Al-Zaidi, E. A. N. (2022). Serological and histological evaluation of the effect of honeybee venom on pancreas and liver in diabetic mice. Archives of Razi Institute, 77(3), 1125–1131. https://doi.org/10.22092/ARI.2022.357385.2025
  • Anapali, M., Kaya-Dagistanli, F., Akdemir, A. S., Aydemir, D., Ulusu, N. N., Ulutin, T., Uysal, O., Tanriverdi, G., & Ozturk, M. (2022). Combined resveratrol and vitamin D treatment ameliorate inflammation-related liver fibrosis, ER stress, and apoptosis in a high-fructose diet/streptozotocin-induced T2DM model. Histochemistry and Cell Biology, 158(3), 279–296. https://doi.org/10.1007/s00418-022-02131-y
  • Arte, P. A., Tungare, K., Bhori, M., Jobby, R., & Aich, J. (2024). Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach. In Human Cell, 37(1):54-84. https://doi.org/10.1007/s13577-023-01007-0
  • Burrack, A. L., Martinov, T., & Fife, B. T. (2017). T cell-mediated beta cell destruction: Autoimmunity and alloimmunity in the context of type 1 diabetes. In Frontiers in Endocrinology, 8, 343. https://doi.org/10.3389/fendo.2017.00343
  • Caturano, A., D’Angelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., Galiero, R., Rinaldi, L., Vetrano, E., Marfella, R., Monda, M., Giordano, A., & Sasso, F. C. (2023). Oxidative stress in type 2 diabetes: Impacts from pathogenesis to lifestyle modifications. In Current Issues in Molecular Biology, 45(8), 6651–6666. https://doi.org/10.3390/cimb45080420
  • Crofts, C. A. P. (2015). Hyperinsulinemia: A unifying theory of chronic disease? Diabesity, 6, 35. https://doi.org/10.15562/diabesity.2015.19
  • El-Megharbel, S. M., Al-Baqami, N. M., Al-Thubaiti, E. H., Qahl, S. H., Albogami, B., & Hamza, R. Z. (2022). Antidiabetic drug sitagliptin with divalent transition metals manganese and cobalt: Synthesis, structure, characterization antibacterial and antioxidative effects in liver tissues. Current Issues in Molecular Biology, 44(5), 1810–1827. https://doi.org/10.3390/cimb44050124
  • Gao, L., Wang, X., Guo, L., Zhang, W., Wang, G., Han, S., & Zhang, Y. (2024). Sex differences in diabetes‑induced hepatic and renal damage. Experimental and Therapeutic Medicine, 27(4), 148. https://doi.org/10.3892/etm.2024.12436
  • Hou, Y., Ding, W., Wu, P., Liu, C., Ding, L., Liu, J., & Wang, X. (2022). Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation. Stem Cell Research and Therapy, 13(1), 132. https://doi.org/10.1186/s13287-022-02760-z
  • Isildar, B., Ozkan, S., Ercin, M., Oktayoglu, S. G., Oncul, M., & Koyuturk, M. (2022). 2D and 3D cultured human umbilical cord ‑ derived mesenchymal stem cell ‑ conditioned medium has a dual effect in type 1 diabetes model in rats : immunomodulation and beta ‑ cell regeneration. Inflammation and Regeneration, 42(1), 55. https://doi.org/10.1186/s41232-022-00241-7
  • Izadi, M., Sadr Hashemi Nejad, A., Moazenchi, M., Masoumi, S., Rabbani, A., Kompani, F., Hedayati Asl, A. A., Abbasi Kakroodi, F., Jaroughi, N., Mohseni Meybodi, M. A., Setoodeh, A., Abbasi, F., Hosseini, S. E., Moeini Nia, F., Salman Yazdi, R., Navabi, R., Hajizadeh-Saffar, E., & Baharvand, H. (2022). Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial. Stem Cell Research & Therapy, 13(1), 264. https://doi.org/10.1186/s13287-022-02941-w
  • Kim, E., Sohn, S., Lee, M., Jung, J., Kineman, R. D., & Park, S. (2006). Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes. Journal of Endocrinology, 188(2), 263–270. https://doi.org/10.1677/joe.1.06501
  • LeFort, K. R., Rungratanawanich, W., & Song, B. J. (2024). Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction. In Cellular and Molecular Life Sciences, 81(1), 34. https://doi.org/10.1007/s00018-023-05061-7
  • Metwally, M. M. M., Ebraheim, L. L. M., & Galal, A. A. A. (2018). Potential therapeutic role of melatonin on STZ-induced diabetic central neuropathy: A biochemical, histopathological, immunohistochemical and ultrastructural study. Acta Histochemica, 120(8), 828–836. https://doi.org/10.1016/j.acthis.2018.09.008
  • Päth, G., Perakakis, N., Mantzoros, C. S., & Seufert, J. (2019). Stem cells in the treatment of diabetes mellitus — Focus on mesenchymal stem cells. Metabolism: Clinical and Experimental, 90, 1–15. https://doi.org/10.1016/j.metabol.2018.10.005
  • Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., & Williams, R. (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice, 157, 107843. https://doi.org/10.1016/j.diabres.2019.107843
  • Su, W., Yu, S., Yin, Y., Li, B., Xue, J., Wang, J., Gu, Y., Zhang, H., Lyu, Z., Mu, Y., & Cheng, Y. (2022). Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats. Stem Cell Research and Therapy, 13(1), 422. https://doi.org/10.1186/s13287-022-03114-5
  • Wu, H., & Mahato, R. I. (2014). Mesenchymal stem cell-based therapy for type 1 diabetes. Discovery Medicine, 17(93), 139–143.
  • Xie, Y., Zhong, K. B., Hu, Y., Xi, Y. L., Guan, S. X., Xu, M., Lin, Y., Liu, F. Y., Zhou, W. J., & Gao, Y. (2022). Liver infiltration of multiple immune cells during the process of acute liver injury and repair. World Journal of Gastroenterology, 28(46), 6537–6550. https://doi.org/10.3748/wjg.v28.i46.6537
  • Yang, H., Yang, T., Heng, C., Zhou, Y., Jiang, Z., Qian, X., Du, L., Mao, S., Yin, X., & Lu, Q. (2019). Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice. Phytotherapy Research, 3(12), 3140–3152. https://doi.org/10.1002/ptr.6486
  • Ye, H., Sun, M., Jin, Z., Yuan, Y., & Weng, H. (2023). FTY-720 alleviates diabetes-induced liver injury by inhibiting oxidative stress and inflammation. Fundamental and Clinical Pharmacology, 37(5), 960–970. https://doi.org/10.1111/fcp.12897
  • Yuniartha, R., Arfian, N., Setyaningsih, W. A. W., Kencana, S. M. S., & Sari, D. C. R. (2022). Accelerated senescence and apoptosis in the rat liver during the progression of diabetic complications. Malaysian Journal of Medical Sciences, 29(6), 46–59. https://doi.org/10.21315/mjms2022.29.6.5

Investigating Oxidative Stress and Histopathological Changes in The Liver of Hyperglycemic Rats

Yıl 2025, Cilt: 14 Sayı: 1, 101 - 106, 28.03.2025

Öz

Objective: This study aimed to investigate the impact of hyperglycemia on the liver in rats. Materials and Methods: An experimental diabetes was created by intraperitoneal streptozotocin administration to Sprague-Dawley rats, and blood glucose levels over 250 dl/kg were counted as diabetic. The experiment was continued for 6 weeks, and weight and blood glucose were observed weekly. After sacrification, liver tissues were fixed with formaldehyde and enclosed in paraffin for histological analysis. Hematoxylin and eosin staining was carried out on 4 µm sections taken from paraffin blocks, and the sections were evaluated histopathologically. At the same time, apoptosis was examined immunohistochemically in those sections by active caspase-3 labeling. Finally, oxidative stress status in liver tissue was analyzed by hydrogen peroxide (H2O2) and superoxide dismutase (SOD) levels. Results: The results revealed a significant elevation in H2O2 levels and a slight decline in SOD levels in the liver tissues in the hyperglycemia group. Additionally, apoptotic hepatocyte numbers were elevated. Histopathological analysis revealed disrupted lobular structure, dilatation of the central vein and sinusoids, hepatocyte shrinkage, and lymphocytic infiltration in the hyperglycemia group. Conclusion: This study underscores the critical role of apoptosis and oxidative stress in liver dysfunction caused by diabetes, highlighting the need for novel therapeutic strategies to protect against hyperglycemia-induced liver damage and improve outcomes for diabetic patients.

Etik Beyan

Institution: Bezmialem Vakıf University Local Ethics Committee Date: 31.10.2024 Approval no: 1293-1/ 31.10.2024-E.169810

Destekleyen Kurum

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Kaynakça

  • Adu, M. D., Malabu, U. H., Malau-Aduli, A. E. O., & Malau-Aduli, B. S. (2019). Enablers and barriers to effective diabetes self-management: A multi-national investigation. PLoS ONE, 14(6), e0217771. https://doi.org/10.1371/journal.pone.0217771
  • Al-Shaeli, S. J. J., Ethaeb, A. M., & Al-Zaidi, E. A. N. (2022). Serological and histological evaluation of the effect of honeybee venom on pancreas and liver in diabetic mice. Archives of Razi Institute, 77(3), 1125–1131. https://doi.org/10.22092/ARI.2022.357385.2025
  • Anapali, M., Kaya-Dagistanli, F., Akdemir, A. S., Aydemir, D., Ulusu, N. N., Ulutin, T., Uysal, O., Tanriverdi, G., & Ozturk, M. (2022). Combined resveratrol and vitamin D treatment ameliorate inflammation-related liver fibrosis, ER stress, and apoptosis in a high-fructose diet/streptozotocin-induced T2DM model. Histochemistry and Cell Biology, 158(3), 279–296. https://doi.org/10.1007/s00418-022-02131-y
  • Arte, P. A., Tungare, K., Bhori, M., Jobby, R., & Aich, J. (2024). Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach. In Human Cell, 37(1):54-84. https://doi.org/10.1007/s13577-023-01007-0
  • Burrack, A. L., Martinov, T., & Fife, B. T. (2017). T cell-mediated beta cell destruction: Autoimmunity and alloimmunity in the context of type 1 diabetes. In Frontiers in Endocrinology, 8, 343. https://doi.org/10.3389/fendo.2017.00343
  • Caturano, A., D’Angelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., Galiero, R., Rinaldi, L., Vetrano, E., Marfella, R., Monda, M., Giordano, A., & Sasso, F. C. (2023). Oxidative stress in type 2 diabetes: Impacts from pathogenesis to lifestyle modifications. In Current Issues in Molecular Biology, 45(8), 6651–6666. https://doi.org/10.3390/cimb45080420
  • Crofts, C. A. P. (2015). Hyperinsulinemia: A unifying theory of chronic disease? Diabesity, 6, 35. https://doi.org/10.15562/diabesity.2015.19
  • El-Megharbel, S. M., Al-Baqami, N. M., Al-Thubaiti, E. H., Qahl, S. H., Albogami, B., & Hamza, R. Z. (2022). Antidiabetic drug sitagliptin with divalent transition metals manganese and cobalt: Synthesis, structure, characterization antibacterial and antioxidative effects in liver tissues. Current Issues in Molecular Biology, 44(5), 1810–1827. https://doi.org/10.3390/cimb44050124
  • Gao, L., Wang, X., Guo, L., Zhang, W., Wang, G., Han, S., & Zhang, Y. (2024). Sex differences in diabetes‑induced hepatic and renal damage. Experimental and Therapeutic Medicine, 27(4), 148. https://doi.org/10.3892/etm.2024.12436
  • Hou, Y., Ding, W., Wu, P., Liu, C., Ding, L., Liu, J., & Wang, X. (2022). Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation. Stem Cell Research and Therapy, 13(1), 132. https://doi.org/10.1186/s13287-022-02760-z
  • Isildar, B., Ozkan, S., Ercin, M., Oktayoglu, S. G., Oncul, M., & Koyuturk, M. (2022). 2D and 3D cultured human umbilical cord ‑ derived mesenchymal stem cell ‑ conditioned medium has a dual effect in type 1 diabetes model in rats : immunomodulation and beta ‑ cell regeneration. Inflammation and Regeneration, 42(1), 55. https://doi.org/10.1186/s41232-022-00241-7
  • Izadi, M., Sadr Hashemi Nejad, A., Moazenchi, M., Masoumi, S., Rabbani, A., Kompani, F., Hedayati Asl, A. A., Abbasi Kakroodi, F., Jaroughi, N., Mohseni Meybodi, M. A., Setoodeh, A., Abbasi, F., Hosseini, S. E., Moeini Nia, F., Salman Yazdi, R., Navabi, R., Hajizadeh-Saffar, E., & Baharvand, H. (2022). Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial. Stem Cell Research & Therapy, 13(1), 264. https://doi.org/10.1186/s13287-022-02941-w
  • Kim, E., Sohn, S., Lee, M., Jung, J., Kineman, R. D., & Park, S. (2006). Differential responses of the growth hormone axis in two rat models of streptozotocin-induced insulinopenic diabetes. Journal of Endocrinology, 188(2), 263–270. https://doi.org/10.1677/joe.1.06501
  • LeFort, K. R., Rungratanawanich, W., & Song, B. J. (2024). Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction. In Cellular and Molecular Life Sciences, 81(1), 34. https://doi.org/10.1007/s00018-023-05061-7
  • Metwally, M. M. M., Ebraheim, L. L. M., & Galal, A. A. A. (2018). Potential therapeutic role of melatonin on STZ-induced diabetic central neuropathy: A biochemical, histopathological, immunohistochemical and ultrastructural study. Acta Histochemica, 120(8), 828–836. https://doi.org/10.1016/j.acthis.2018.09.008
  • Päth, G., Perakakis, N., Mantzoros, C. S., & Seufert, J. (2019). Stem cells in the treatment of diabetes mellitus — Focus on mesenchymal stem cells. Metabolism: Clinical and Experimental, 90, 1–15. https://doi.org/10.1016/j.metabol.2018.10.005
  • Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., & Williams, R. (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice, 157, 107843. https://doi.org/10.1016/j.diabres.2019.107843
  • Su, W., Yu, S., Yin, Y., Li, B., Xue, J., Wang, J., Gu, Y., Zhang, H., Lyu, Z., Mu, Y., & Cheng, Y. (2022). Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats. Stem Cell Research and Therapy, 13(1), 422. https://doi.org/10.1186/s13287-022-03114-5
  • Wu, H., & Mahato, R. I. (2014). Mesenchymal stem cell-based therapy for type 1 diabetes. Discovery Medicine, 17(93), 139–143.
  • Xie, Y., Zhong, K. B., Hu, Y., Xi, Y. L., Guan, S. X., Xu, M., Lin, Y., Liu, F. Y., Zhou, W. J., & Gao, Y. (2022). Liver infiltration of multiple immune cells during the process of acute liver injury and repair. World Journal of Gastroenterology, 28(46), 6537–6550. https://doi.org/10.3748/wjg.v28.i46.6537
  • Yang, H., Yang, T., Heng, C., Zhou, Y., Jiang, Z., Qian, X., Du, L., Mao, S., Yin, X., & Lu, Q. (2019). Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice. Phytotherapy Research, 3(12), 3140–3152. https://doi.org/10.1002/ptr.6486
  • Ye, H., Sun, M., Jin, Z., Yuan, Y., & Weng, H. (2023). FTY-720 alleviates diabetes-induced liver injury by inhibiting oxidative stress and inflammation. Fundamental and Clinical Pharmacology, 37(5), 960–970. https://doi.org/10.1111/fcp.12897
  • Yuniartha, R., Arfian, N., Setyaningsih, W. A. W., Kencana, S. M. S., & Sari, D. C. R. (2022). Accelerated senescence and apoptosis in the rat liver during the progression of diabetic complications. Malaysian Journal of Medical Sciences, 29(6), 46–59. https://doi.org/10.21315/mjms2022.29.6.5
Toplam 23 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlığın Geliştirilmesi, Veteriner Histoloji ve Embriyolojisi
Bölüm Makaleler
Yazarlar

Başak Işıldar 0000-0001-7557-7611

Meral Koyutürk 0000-0002-0270-5069

Yayımlanma Tarihi 28 Mart 2025
Gönderilme Tarihi 29 Ocak 2025
Kabul Tarihi 14 Mart 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 14 Sayı: 1

Kaynak Göster

APA Işıldar, B., & Koyutürk, M. (2025). Investigating Oxidative Stress and Histopathological Changes in The Liver of Hyperglycemic Rats. Balıkesir Sağlık Bilimleri Dergisi, 14(1), 101-106. https://doi.org/10.53424/balikesirsbd.1628944

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