Study on the apoptosis and Histopathology of the Heart following Renal Ischemia Time-Dependent Reperfusion in Male Rats
Mahbod Bazhban
1
(
Graduate of Veterinary Medicine, Faculty of Veterinary Medicine, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran
)
, Yousef Doustar
2
(
Associate Professor, Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran.
)
M.A Nourazar
3
(
Assostant Professor, Department of Basic Sciences, Faculty of Veterinary Medicine, Tabriz Medical Sciences, Islamic Azad University, Tabriz, Iran.
)
Keywords: ischemia-reperfusion, kidney, heart, rat, Apoptosis.,
Abstract :
Kidney ischemia-reperfusion injury (I/R) is one of the most important causes of acute renal failure and subsequent damage to other organs such as the heart. was to investigate the occurrence of damage and apoptosis in the heart following renal ischemia-reperfusion time-dependent injury in rats. For this purpose, 32 male Wistar rats were randomly divided into 4 equal groups. In the first group (Sham), only the surgical site was opened and closed. In the second group (30-I/R) after the induction of renal ischemia, reperfusion was performed 30 minutes later, in the third group (45-I/R) 45 minutes later, and in the fourth group (60-I/R) 60 minutes later. After 24 hours, all animals were euthanized and their kidney and heart tissues were sampled for microscopic study. Statistical analysis of the data was done by one-way analysis of variance (ANOVA) and Tukey's post-test, and values of p<0.05 were considered significant.Histopathological findings showed renal damage following I/R in the form of degenerative changes and necrosis of proximal and distal tubules, glomerular and interstitial tissue damage in a time-dependent manner. Also, renal I/R resulted in heart tissue damage including degenerative changes and necrosis along with apoptosis of cardiomyocytes in all groups, but the severity of tissue damage and apoptosis of cardiomyocytes in the 60-I/R group was significantly higher than other groups (p<0.05). The results of the study showed that by reducing the duration of renal ischemia, the damages to the kidney tissue and subsequently heart tissue as well as apoptosis of cardiomyocytes will be less.
Akcay, A., Nguyen, Q. and Edelstein, C.L. (2009). Mediators of inflammation in acute kidney injury. Mediators of inflammation, 200: 137072.
Alihemmati, A., Yousefi, H., Ahmadiasl, N. and Habibi, P. (2018). Apoptosis and histopathology of the heart after renal ischemia-reperfusion in male rat running title: ischemia-reperfusion injury. Brazilian Archives of Biology and Technology, 60.
Bhalodia, Y., Kanzariya, N., Patel, R., Patel, N., Vaghasiya, J., Jivani, N., et al. (2009). Renoprotective activity of benincasa cerifera fruit extract on ischemia/reperfusion-induced renal damage in rat. International Journal of Kidney Diseases, 2009, 3(2): 80
Doi, K. and Rabb, H. (2016). Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. Kidney international, 89(3): 555-564.
Druml, W. (2014). Systemic consequences of acute kidney injury. Current opinion in critical care, 20(6): 613-619.
El-Abhar, H.S., Abdallah, D.M. and Saleh, S. (2003). Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. Journal of ethnopharmacology, 84(2-3): 251-258.
Garcia-Criado, F.J., Eleno, N., Santos-Benito, F., Valdunciel, J.J., Reverte, M., Lozano-Sanchez, F.S., et al. (1998). protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion. Transplantation, 66(8): 982-990.
Grams, M.E. and Rabb, H. (2012). The distant organ effects of acute kidney injury. Kidney international, 81(10): 942-948.
Hassoun, H.T., Grigoryev, D.N., Lie, M.L., Liu, M., Cheadle, C., Tuder, R.M., et al. (2007). Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. American Journal of Physiology-Renal Physiology, 293(1): F30-F40.
Husain-Syed, F., Rosner, M.H. and Ronco, C. (2020). Distant organ dysfunction in acute kidney injury. Acta Physiologica, 228(2): e13357.
Joukar, S., Bashiri, H., Dabiri, S., Ghotbi, P., Sarveazad, A., Divsalar, K., et al. (2012): Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury. Journal of physiology and biochemistry. 68(2): 271-279.
Karimi, N., Haghani, M., Noorafshan, A. and Moosavi, S.M.S. (2017). Structural and functional disorders of hippocampus following ischemia/reperfusion in lower limbs and kidneys. Neuroscience, 358: 238-248.
Kelly, K.J. (2003). Distant effects of experimental renal ischemia/reperfusion injury. Journal of the American Society of Nephrology, 14(6): 1549-1558.
Kikuchi, S., Matsumoto, H. and Ito, M. (1983). Free amino acid changes in the cerebral cortex of experimental uremic rat. Neurochemical Research, 8(3): 313-318.
Kirkby, K., Baylis, C., Agarwal, A., Croker, B., Archer, L. and Adin, C. (2007). Intravenous bilirubin provides incomplete protection against renal ischemia-reperfusion injury in vivo. American Journal of Physiology-Renal Physiology, 292(2): F888-F894.
Lane, K., Dixon, J.J., MacPhee, I.A. and Philips, B.J. (2013). Renohepatic crosstalk: does acute kidney injury cause liver dysfunction?. Nephrology dialysis transplantation, 28(7): 1634-1647.
Lawrence, T. (2009). The nuclear factor NF-κB pathway in inflammation. Cold Spring Harbor perspectives in biology, 1(6): a001651.
Lee, D.W., Faubel, S. and Edelstein, C. (2011). Cytokines in acute kidney injury (AKI). Clinical nephrology, 76(3): 165-173.
Legrand, M., Mik, E.G., Johannes, T., Payen, D. and Ince, C. (2008). Renal hypoxia and dysoxia after reperfusion of the ischemic kidney. Molecular medicine, 14(7-8): 502-516.
Li, J., Hong, Z., Liu, H., Zhou, J., Cui, L., Yuan, S., Chu, X. and Yu, P.(2016). Hydrogen-rich saline promotes the recovery of renal function after ischemia/reperfusion injury in rats via anti-apoptosis and anti-inflammation. Frontiers in pharmacology, 7: 106.
Liu, M., Liang, Y., Chigurupati, S., Lathia, J.D., Pletnikov, M., Sun, Z., et al. (2008). Acute kidney injury leads to inflammation and functional changes in the brain. Journal of the American Society of Nephrology: JASN, 19(7): 1360.
Liu, Y., Shi, B., Li, Y. and Zhang, H. (2017). Protective effect of luteolin against renal ischemia/reperfusion injury via modulation of pro-inflammatory cytokines, oxidative stress and apoptosis for possible benefit in kidney transplant. Medical science monitor: international medical journal of experimental and clinical research, 23: 5720-5727.
Miyazawa, S., Watanabe, H., Miyaji, C., Hotta, O. and Abo, T. (2002). Leukocyte accumulation and changes in extra-renal organs during renal ischemia reperfusion in mice. Journal of Laboratory and Clinical Medicine, 139(5): 269-278.
Mohajeri, D., Gharamaleki, M.N., Hejazi, S.S. and Nazeri, M. (2013). Preventive effects of turnip (Brassica rapa L.) on renal ischemia-reperfusion injury in rats. Life Science Journal, 10(1): 1165-1170.
Mohsen, N., Mahmoud, P., Pejman, S., Mohammed, G., Masoud, S., Ali, T., et al. (2010). Effects of stem cells and granulocyte colony stimulating factor in reperfusion injury. Iranian Journal of Kidney Diseases 4 (3): 207-13.
Ologunde, R., Zhao, H., Lu, K. and Ma, D. (2014). Organ cross talk and remote organ damage following acute kidney injury. International urology and nephrology, 46(12) :2337-2345.
Park, S.W., Chen, S.W., Kim, M., Brown, K.M., Kolls, J.K., D D'Agati, V., et al. (2011). Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy. Laboratory investigation, 91(1): 63-84.
Patschan, D., Patschan, S. and Müller, G.A. (2012). Inflammation and microvasculopathy in renal ischemia reperfusion injury. Journal of transplantation, 2012: 1-7.
Quoilin, C., Mouithys-Mickalad, A., Lécart, S., Fontaine-Aupart, M.P. and Hoebeke, M. (2014). Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1837(10): 1790-1800.
Sancaktutar, A.A., Bodakci, M.N., Hatipoglu, N.K., Soylemez, H., Basarılı, K. and Turkcu, G. (2014). The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats. Urology annals, 6(1): 46.
Scaini, G., Ferreira, G.K. and Streck, E.L. (2010). Mechanisms underlying uremic encephalopathy. Revista Brasileira de terapia intensiva, 22: 206-211.
Scheel, P.J., Liu, M. and Rabb, H. (2008). Uremic lung: new insights into a forgotten condition. Kidney international, 74(7): 849-851.
Shang, Y., Siow, Y.L. and Isaak, C.K. (2016). Downregulation of glutathione biosynthesis contributes to oxidative stress and liver dysfunction in acute kidney injury. Oxidative Medicine and Cellular Longevity, 2016, 1-13.
Sung, F.L., Zhu, T.Y., Au-Yeung, K.K., Siow, Y.L. and Karmin, O. (2002). Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by oxidative stress and NF-κB. Kidney international, 62(4): 1160-1170.
Thurman, J.M. (2007). Triggers of inflammation after renal ischemia/reperfusion. Clinical immunology, 123(1): 7-13.
Wang, P., Zhu, Q., Wu, N., Siow, Y.L., Aukema, H. and O, K. (2013). Tyrosol Attenuates Ischemia–Reperfusion-Induced Kidney Injury via Inhibition of Inducible Nitric Oxide Synthase. Journal of agricultural and food chemistry, 61(15): 3669-3675.
Yap, S.C., Lee, H.T. and Warner, D.S. (2012). Acute kidney injury and extrarenal organ dysfunction: new concepts and experimental evidence. The Journal of the American Society of Anesthesiologists, 116(5): 1139-1148.
