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BÖBREK İSKEMİ-REPERFÜZYON HASARINDA KALPAİN İNHİBİTÖRÜ OLAN AK295 UYGULANAN SIÇANLARDA SERUM ÜRE VE KREATİN DEĞERLERİ

Year 2022, Volume: 10 Issue: 1, 335 - 344, 10.03.2022

Songül Aydemir , Mahmut Binen

https://doi.org/10.33715/inonusaglik.1021152

Abstract

Nekroz ve apoptoz gibi hücre ölümü ile sonuçlanan olaylarda kalpainler, kaspazlarla birlikte çalışan proteazlardır. Sıçan omurilik travma modellerinde kalpain inhibitörlerinin (AK295) apoptozu yavaşlattığı veya durdurduğu bilinmektedir. Bu çalışmada 28 adet erkek wistar albino sıçan rastgele seçilerek dört gruba ayrıldı. Gruplar; kontrol, İskemi-Reperfüzyon (İ/R), İskemi-Reperfüzyon+AK295, İskemi-Reperfüzyon+DMSO (dimetil sülfoksit) olarak belirlendi. İskemi sonrasında böbreklerde oluşan hasarda kalpain inhibitörü olan AK295’in etkisi incelendi. Sıçanlara sağ böbrek nefrektomisi uygulanarak 30 dakika total iskemi yapıldı. 24 saatlik reperfüzyon periyodu tamamlandıktan sonra anestezi uygulandı. Bu çalışmamızda, böbrek hasarında önemli indikatörler olan serum kreatin ve üre değerleri tayin edildi. Kontrol, I/R, I/R + AK295, and I/R + DMSO gruplarında ortalama üre değerleri; sırasıyla 35.4 ± 22.3, 156.4 ± 9.01, 150.8 ± 5.8, ve 165.2 ± 6.1 mg/dL olarak bulundu. İ/R + AK295 ve İ/R + DMSO değerlerinin, kontrol grubuna göre anlamlı (p<0.05) derecede yüksek olduğu bulunmuştur. Böbrekte İ/R oluşturulan sıçanlarda, AK295’in oluşan böbrek hasarını kısmen azalttığı tespit edildi.

Keywords

AK295 Böbrek İskemi-Reperfüzyon Kalpain inhibitörü

Supporting Institution

İnönü Üniversitesi

Project Number

2009/48

Thanks

Bu projeyi destekleyen İnönü Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi'ne teşekkür ediyorum.

References

  • Akdemir, O., Uçankale, M., Karaoğlan, A., Barut, S., Sağmanligil, A., Bilguvar, K., ...Colak, A. (2008). Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury. Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia, 15(10), 1130–1136. https://doi.org/10.1016/j.jocn.2007.08.011
  • Aragno, M., Cutrin, J. C., Mastrocola, R., Perrelli, M. G., Restivo, F., Poli, G., …Boccuzzi, G. (2003). Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone. Kidney international, 64(3), 836–843. https://doi.org/10.1046/j.1523-1755.2003.00152.x
  • Blight, A. R., Zimber, M. P. (2001). Acute spinal cord injury: pharmacotherapy and drug development perspectives. Current opinion in investigational drugs (London, England : 2000), 2(6), 801–808.
  • Chatterjee, P. K., Brown, P. A., Cuzzocrea, S., Zacharowski, K., Stewart, K. N., Mota-Filipe, H., … Thiemermann, C. (2001). Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat. Kidney international, 59(6), 2073–2083. https://doi.org/10.1046/j.1523-1755.2001.00722.x
  • Chatterjee, P. K., Patel, N. S., Kvale, E. O., Cuzzocrea, S., Brown, P. A., Stewart, K. N., … Thiemermann, C. (2002). Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury. Kidney international, 61(3), 862–871. https://doi.org/10.1046/j.1523-1755.2002.00234.x
  • Chowdhury, P., Sacks, S. H., Sheerin, N. S. (2004). Minireview: functions of the renal tract epithelium in coordinating the innate immune response to infection. Kidney international, 66(4), 1334–1344. https://doi.org/10.1111/j.1523-1755.2004.00896.x
  • Çolak, A., Kaya, M., Karaoğlan, A., Sağmanligil, A., Akdemir, O., Sahan, E., Celik, O. (2009). Calpain inhibitor AK 295 inhibits calpain-induced apoptosis and improves neurologic function after traumatic spinal cord injury in rats. Neurocirugia (Asturias, Spain), 20(3), 245–254.
  • Croall, D. E., DeMartino, G. N. (1991). Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiological reviews, 71(3), 813–847. https://doi.org/10.1152/physrev.1991.71.3.813
  • Friedewald, J. J., Rabb, H. (2004). Inflammatory cells in ischemic acute renal failure. Kidney international, 66(2), 486–491. https://doi.org/10.1111/j.1523-1755.2004.761_3.x
  • Goll, D. E., Thompson, V. F., Li, H., Wei, W., Cong, J. (2003). The calpain system. Physiological reviews, 83(3), 731–801. https://doi.org/10.1152/physrev.00029.2002
  • Hai S, Takemura S, Minamiyama Y, Yamasaki K, Yamamoto S, Kodai S, …Suehiro S. Mitochondrial K(ATP) channel opener prevents ischemia-reperfusion injury in rat liver. Transplant Proc. 2005 Jan-Feb;37(1) 428-431. doi:10.1016/j.transproceed.2004.12.112. PMID: 15808666.
  • Hong, S. C., Goto, Y., Lanzino, G., Soleau, S., Kassell, N. F., Lee, K. S. (1994). Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia. Stroke, 25(3), 663–669. https://doi.org/10.1161/01.str.25.3.663
  • Kahraman, A., Erkasap, N., Serteser, M., Köken, T. (2003). Protective effect of quercetin on renal ischemia/reperfusion injury in rats. Journal of nephrology, 16(2), 219–224.
  • Kalogeris, T., Baines, C. P., Krenz, M., Korthuis, R. J. (2012). Cell biology of ischemia/reperfusion injury. International review of cell and molecular biology, 298, 229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7
  • Karimi, G., Ramezani, M., Tahoonian, Z. (2005). Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evidence-based complementary and alternative medicine : eCAM, 2(3), 383–386. https://doi.org/10.1093/ecam/neh103
  • Khalil, A. A., Aziz, F. A., Hall, J. C. (2006). Reperfusion injury. Plastic and reconstructive surgery, 117(3), 1024–1033. https://doi.org/10.1097/01.prs.0000204766.17127.54
  • Saatman, K. E., Murai, H., Bartus, R. T., Smith, D. H., Hayward, N. J., Perri, B. R.,McIntosh, T. K. (1996). Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat. Proceedings of the National Academy of Sciences of the United States of America, 93(8), 3428–3433. https://doi.org/10.1073/pnas.93.8.3428
  • Saez, M. E., Ramirez-Lorca, R., Moron, F. J., Ruiz, A. (2006). The therapeutic potential of the calpain family: new aspects. Drug discovery today, 11(19-20), 917–923. https://doi.org/10.1016/j.drudis.2006.08.009
  • Serracino-Inglott, F., Habib, N. A., Mathie, R. T. (2001). Hepatic ischemia-reperfusion injury. American journal of surgery, 181(2), 160–166. https://doi.org/10.1016/s0002-9610(00)00573-0
  • Shiva, N., Sharma, N., Kulkarni, Y. A., Mulay, S. R., Gaikwad, A. B. (2020). Renal ischemia/reperfusion injury: An insight on in vitro and in vivo models. Life sciences, 256, 117860. https://doi.org/10.1016/j.lfs.2020.117860
  • Sorimachi, H., & Suzuki, K. (2001). The structure of calpain. Journal of biochemistry, 129(5), 653–664. https://doi.org/10.1093/oxfordjournals.jbchem.a002903
  • Suzuki, K., Hata, S., Kawabata, Y., Sorimachi, H. (2004). Structure, activation, and biology of calpain. Diabetes, 53 Suppl 1, S12–S18. https://doi.org/10.2337/diabetes.53.2007.s12
  • Thiemermann, C., Patel, N. S., Kvale, E. O., Cockerill, G. W., Brown, P. A., Stewart, K. N., Cuzzocrea, S., … Chatterjee, P. K. (2003). High density lipoprotein (HDL) reduces renal ischemia/reperfusion injury. Journal of the American Society of Nephrology : JASN, 14(7), 1833–1843. https://doi.org/10.1097/01.asn.0000075552.97794.8c
  • Viñas, J. L., Sola, A., Genescà, M., Alfaro, V., Pí, F., Hotter, G. (2006). NO and NOS isoforms in thedevelopment of apoptosis in renal ischemia/reperfusion. Free radical biology & medicine, 40(6), 992–1003. https://doi.org/10.1016/j.freeradbiomed.2005.10.046
  • Wang, K. K., Yuen, P. W. (1997). Development and therapeutic potential of calpain inhibitors. Advances in pharmacology (San Diego, Calif.), 37, 117–152. https://doi.org/10.1016/s1054-3589(08)60949-7
  • Wei, Q., Dong, Z. (2012). Mouse model of ischemic acute kidney injury: technical notes and tricks. American journal of physiology. Renal physiology, 303(11), F1487–F1494. https://doi.org/10.1152/ajprenal.00352.2012
  • Yazihan, N., Ataoglu, H., Kavas, G. O., Akyurek, N., Yener, B., Aydm, C. (2008). The effect of K-ATP channel blockage during erythropoietin treatment in renal ischemia-reperfusion injury. Journal of investigative surgery : the official journal of the Academy of Surgical Research, 21(6), 340–347. https://doi.org/10.1080/08941930802438906

Serum Urea and Creatin Values in Rats Administered with AK295, a Calpain Inhibitor, in Renal Ischemia-Reperfusion Injury

Year 2022, Volume: 10 Issue: 1, 335 - 344, 10.03.2022

Songül Aydemir , Mahmut Binen

https://doi.org/10.33715/inonusaglik.1021152

Abstract

In events that result in cell death such as necrosis and apoptosis, calpains are proteases functioning with caspases. Calpain inhibitors (AK295) are known to slow down or stop apoptosis in spinal cord trauma models in rats. In this study, 28 male Wistar albino rats were randomly selected and divided into four groups. Groups were determined as; control, Ischemia-Reperfusion (I/R), Ischemia-Reperfusion+AK295, Ischemia-Reperfusion+DMSO (dimethyl sulfoxide). On kidney damage after ischemia, the effect of AK295, a calpain inhibitor, was investigated. 30 minutes total ischemia was performed following right kidney nephrectomy application to rats. Anesthesia was administered after the reperfusion for 24-hour was completed. The serum creatinine and urea values, which are important indicators in kidney damage, were measured. The mean urea values in the groups of control, I/R, I/R + AK295, and I/R + DMSO were measured as 35.4 ± 22.3, 156.4 ± 9.01, 150.8 ± 5.8, and 165.2 ± 6.1 mg/dL, respectively. It has been determined that the results of groups I/R+AK295 and I/R+DMSO were statistically significantly higher than those of the control group (p<0.05). It was determined that the AK295 partly reduced kidney injury in rats, which have been performed renal IR.

Keywords

AK295 Calpain inhibitor Ischemia-Reperfusion Kidney

Project Number

2009/48

References

  • Akdemir, O., Uçankale, M., Karaoğlan, A., Barut, S., Sağmanligil, A., Bilguvar, K., ...Colak, A. (2008). Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury. Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia, 15(10), 1130–1136. https://doi.org/10.1016/j.jocn.2007.08.011
  • Aragno, M., Cutrin, J. C., Mastrocola, R., Perrelli, M. G., Restivo, F., Poli, G., …Boccuzzi, G. (2003). Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone. Kidney international, 64(3), 836–843. https://doi.org/10.1046/j.1523-1755.2003.00152.x
  • Blight, A. R., Zimber, M. P. (2001). Acute spinal cord injury: pharmacotherapy and drug development perspectives. Current opinion in investigational drugs (London, England : 2000), 2(6), 801–808.
  • Chatterjee, P. K., Brown, P. A., Cuzzocrea, S., Zacharowski, K., Stewart, K. N., Mota-Filipe, H., … Thiemermann, C. (2001). Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat. Kidney international, 59(6), 2073–2083. https://doi.org/10.1046/j.1523-1755.2001.00722.x
  • Chatterjee, P. K., Patel, N. S., Kvale, E. O., Cuzzocrea, S., Brown, P. A., Stewart, K. N., … Thiemermann, C. (2002). Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury. Kidney international, 61(3), 862–871. https://doi.org/10.1046/j.1523-1755.2002.00234.x
  • Chowdhury, P., Sacks, S. H., Sheerin, N. S. (2004). Minireview: functions of the renal tract epithelium in coordinating the innate immune response to infection. Kidney international, 66(4), 1334–1344. https://doi.org/10.1111/j.1523-1755.2004.00896.x
  • Çolak, A., Kaya, M., Karaoğlan, A., Sağmanligil, A., Akdemir, O., Sahan, E., Celik, O. (2009). Calpain inhibitor AK 295 inhibits calpain-induced apoptosis and improves neurologic function after traumatic spinal cord injury in rats. Neurocirugia (Asturias, Spain), 20(3), 245–254.
  • Croall, D. E., DeMartino, G. N. (1991). Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiological reviews, 71(3), 813–847. https://doi.org/10.1152/physrev.1991.71.3.813
  • Friedewald, J. J., Rabb, H. (2004). Inflammatory cells in ischemic acute renal failure. Kidney international, 66(2), 486–491. https://doi.org/10.1111/j.1523-1755.2004.761_3.x
  • Goll, D. E., Thompson, V. F., Li, H., Wei, W., Cong, J. (2003). The calpain system. Physiological reviews, 83(3), 731–801. https://doi.org/10.1152/physrev.00029.2002
  • Hai S, Takemura S, Minamiyama Y, Yamasaki K, Yamamoto S, Kodai S, …Suehiro S. Mitochondrial K(ATP) channel opener prevents ischemia-reperfusion injury in rat liver. Transplant Proc. 2005 Jan-Feb;37(1) 428-431. doi:10.1016/j.transproceed.2004.12.112. PMID: 15808666.
  • Hong, S. C., Goto, Y., Lanzino, G., Soleau, S., Kassell, N. F., Lee, K. S. (1994). Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia. Stroke, 25(3), 663–669. https://doi.org/10.1161/01.str.25.3.663
  • Kahraman, A., Erkasap, N., Serteser, M., Köken, T. (2003). Protective effect of quercetin on renal ischemia/reperfusion injury in rats. Journal of nephrology, 16(2), 219–224.
  • Kalogeris, T., Baines, C. P., Krenz, M., Korthuis, R. J. (2012). Cell biology of ischemia/reperfusion injury. International review of cell and molecular biology, 298, 229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7
  • Karimi, G., Ramezani, M., Tahoonian, Z. (2005). Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evidence-based complementary and alternative medicine : eCAM, 2(3), 383–386. https://doi.org/10.1093/ecam/neh103
  • Khalil, A. A., Aziz, F. A., Hall, J. C. (2006). Reperfusion injury. Plastic and reconstructive surgery, 117(3), 1024–1033. https://doi.org/10.1097/01.prs.0000204766.17127.54
  • Saatman, K. E., Murai, H., Bartus, R. T., Smith, D. H., Hayward, N. J., Perri, B. R.,McIntosh, T. K. (1996). Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat. Proceedings of the National Academy of Sciences of the United States of America, 93(8), 3428–3433. https://doi.org/10.1073/pnas.93.8.3428
  • Saez, M. E., Ramirez-Lorca, R., Moron, F. J., Ruiz, A. (2006). The therapeutic potential of the calpain family: new aspects. Drug discovery today, 11(19-20), 917–923. https://doi.org/10.1016/j.drudis.2006.08.009
  • Serracino-Inglott, F., Habib, N. A., Mathie, R. T. (2001). Hepatic ischemia-reperfusion injury. American journal of surgery, 181(2), 160–166. https://doi.org/10.1016/s0002-9610(00)00573-0
  • Shiva, N., Sharma, N., Kulkarni, Y. A., Mulay, S. R., Gaikwad, A. B. (2020). Renal ischemia/reperfusion injury: An insight on in vitro and in vivo models. Life sciences, 256, 117860. https://doi.org/10.1016/j.lfs.2020.117860
  • Sorimachi, H., & Suzuki, K. (2001). The structure of calpain. Journal of biochemistry, 129(5), 653–664. https://doi.org/10.1093/oxfordjournals.jbchem.a002903
  • Suzuki, K., Hata, S., Kawabata, Y., Sorimachi, H. (2004). Structure, activation, and biology of calpain. Diabetes, 53 Suppl 1, S12–S18. https://doi.org/10.2337/diabetes.53.2007.s12
  • Thiemermann, C., Patel, N. S., Kvale, E. O., Cockerill, G. W., Brown, P. A., Stewart, K. N., Cuzzocrea, S., … Chatterjee, P. K. (2003). High density lipoprotein (HDL) reduces renal ischemia/reperfusion injury. Journal of the American Society of Nephrology : JASN, 14(7), 1833–1843. https://doi.org/10.1097/01.asn.0000075552.97794.8c
  • Viñas, J. L., Sola, A., Genescà, M., Alfaro, V., Pí, F., Hotter, G. (2006). NO and NOS isoforms in thedevelopment of apoptosis in renal ischemia/reperfusion. Free radical biology & medicine, 40(6), 992–1003. https://doi.org/10.1016/j.freeradbiomed.2005.10.046
  • Wang, K. K., Yuen, P. W. (1997). Development and therapeutic potential of calpain inhibitors. Advances in pharmacology (San Diego, Calif.), 37, 117–152. https://doi.org/10.1016/s1054-3589(08)60949-7
  • Wei, Q., Dong, Z. (2012). Mouse model of ischemic acute kidney injury: technical notes and tricks. American journal of physiology. Renal physiology, 303(11), F1487–F1494. https://doi.org/10.1152/ajprenal.00352.2012
  • Yazihan, N., Ataoglu, H., Kavas, G. O., Akyurek, N., Yener, B., Aydm, C. (2008). The effect of K-ATP channel blockage during erythropoietin treatment in renal ischemia-reperfusion injury. Journal of investigative surgery : the official journal of the Academy of Surgical Research, 21(6), 340–347. https://doi.org/10.1080/08941930802438906
There are 27 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Araştırma Makalesi
Authors

Songül Aydemir 0000-0002-7921-0662

Mahmut Binen 0000-0002-2158-8427

Project Number 2009/48
Early Pub Date March 4, 2022
Publication Date March 10, 2022
Submission Date November 9, 2021
Acceptance Date February 20, 2022
Published in Issue Year 2022 Volume: 10 Issue: 1

Cite

APA Aydemir, S., & Binen, M. (2022). BÖBREK İSKEMİ-REPERFÜZYON HASARINDA KALPAİN İNHİBİTÖRÜ OLAN AK295 UYGULANAN SIÇANLARDA SERUM ÜRE VE KREATİN DEĞERLERİ. İnönü Üniversitesi Sağlık Hizmetleri Meslek Yüksek Okulu Dergisi, 10(1), 335-344. https://doi.org/10.33715/inonusaglik.1021152
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