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INVESTIGATION OF ANTIOXIDANT AND ANTIAPOPTOTIC EFFECTS OF LERCANIDIPINE IN DOXORUBICIN-INDUCED KIDNEY DAMAGE VIA BCL-2/BAX/SIT C/CAS-3 SIGNALING PATHWAY

Year 2022, Volume: 29 Issue: 4, 671 - 679, 27.12.2022
https://doi.org/10.17343/sdutfd.1198304

Abstract

Objective
Doxorubicin (Dox) is an antineoplastic drug used in
chemotherapy. Nephrotoxicity is one of the important
side effects that limit the use of Dox. It is known that
lercanidipine (Ler), a calcium channel blocker, has antioxidant
and antiapoptotic properties. In our study, we
aimed to evaluate the effects of Lercanidipine (Ler) on
oxidative stress and apoptosis in Dox-induced kidney
damage in rats.
Material and Method
Twenty-four adult male rats were divided into 3 equal
groups: control, Dox (20 mg/kg Dox intraperitoneally
once on day 8) and Dox+Ler (20 mg/kg Dox intraperitoneally
once on day 8, 2 mg/kg Ler by oral gavage
every day for 10 days). At the end of the study, blood
urea nitrogen (BUN) and creatinine levels were measured
from the serum of rats. Also, total oxidant status
(TOS), total antioxidant status (TAS) and superoxide
dismutase (SOD) enzyme activity determined
from kidney tissues. In addition, Bcl-2-associated X
protein (Bax), B-cell-lymphoma-2 (Bcl-2) cytochrome
c (sit c) and caspase-3 (Cas-3) mRNA expression levels
in kidney tissue were analyzed by quantitative
real time polymerase chain reaction method. Also,
histopathological changes were examined by hematoxylin-
eosin staining.
Results
In our study, Dox administration elevated BUN, creatinine,
TOS and oxidative stress index, while decreasing
SOD activity and TAS levels. In addition, while
the expression of proapoptotic markers (Bax, sit c and
Cas-3) increased in the Dox group, the expression of
Bcl-2, an antiapoptotic factor, decreased. In histological
examinations, findings indicating kidney damage
due to Dox exposure were observed. But, the Ler administration
showed protective effects by limiting all
the changes related to Dox in the kidney.
Conclusion
Our study shows that Ler may be a potential candidate
drug for preventing Dox-induced kidney damage
by showing antioxidant and antiapoptotic properties.

References

  • 1. Refaie MM, Amin EF, El-Tahawy NF, Abdelrahman AM. Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats. Journal of toxicology. 2016;2016:9507563.
  • 2. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of pharmacy and pharmacology. 2013;65(2):157-70.
  • 3. Wu Q, Li W, Zhao J, Sun W, Yang Q, Chen C, et al. Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation. Biomedicine & harmacotherapy. 2021;137:111308. 4. Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicology letters. 2019;307:41-8.
  • 5. Özcan O, Erdal H, Çakırca G, Yönden Z. Oksidatif stres ve hücre içi lipit, protein ve DNA yapıları üzerine etkileri. Journal of Clinical and Experimental Investigations. 2015;6(3):331-6.
  • 6. Malarkodi KP, Balachandar AV, Varalakshmi P. The influence of lipoic acid on adriamycin induced nephrotoxicity in rats. Mol Cell Biochem. 2003;247(1-2):15-22.
  • 7. Jha JC, Banal C, Chow BS, Cooper ME, Jandeleit-Dahm K. Diabetes and kidney disease: role of oxidative stress. Antioxidants & redox signaling. 2016;25(12):657-84.
  • 8. Taskin E, Ozdogan K, Kunduz Kindap E, Dursun N. The restoration of kidney mitochondria function by inhibition of angiotensin- II production in rats with acute adriamycin-induced nephrotoxicity. Renal Failure. 2014;36(4):606-12.
  • 9. Atagün G, Zafer E, Gürkanlı İ. Apoptoziste mitokondrinin rolü. Türk Bilimsel Derlemeler Dergisi. 2011(2):9-53.
  • 10. Su Z, Ye J, Qin Z, Ding X. Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro. Scientific reports. 2015;5(1):1-14.
  • 11. Grassi G, Robles NR, Seravalle G, Fici F. Lercanidipine in the management of hypertension: an update. Journal of Pharmacology and Pharmacotherapeutics. 2017;8(4):155-65.
  • 12. Testa R, Leonardi A, Tajana A, Riscassi E, Magliocca R, Sartani A. Lercanidipine (Rec 15/2375): A Novel 1, 4‐Dihydropyridine Calcium Antagonist for Hypertension. Cardiovascular Drug Reviews. 1997;15(3):187-219.
  • 13. Epstein M. Lercanidipine: a novel dihydropyridine calcium-channel blocker. Heart Dis. 2001;3(6):398-407.
  • 14. Bernocchi P, Ceconi C, Cargnoni A, Pedersini P, Boraso A, Curello S, et al. Effects of lercanidipine on Fe2+-induced mitochondrial lipid peroxidation. Journal of Cardiovascular Pharmacology. 1997;29:S63-S72.
  • 15. Vasigar P, Batmanabane M. Anti-inflammatory activity of calcium channel blocker lercanidipine hydrochloride. Journal of Pharmacology and Pharmacotherapeutics. 2013;4(4):238-42.
  • 16. Gupta S, Sharma U, Jagannathan NR, Gupta YK. Neuroprotective effect of lercanidipine in middle cerebral artery occlusion model of stroke in rats. Experimental neurology. 2017;288:25- 37.
  • 17. Ayla S, Seckin I, Tanriverdi G, Cengiz M, Eser M, Soner BC, et al. Doxorubicin induced nephrotoxicity: protective effect of nicotinamide. Int J Cell Biol. 2011;2011:390238.
  • 18. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy. 2016;7(2):27.
  • 19. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.
  • 20. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. 2004;37(4):277-85.
  • 21. Ukeda H, Kawana D, Maeda S, Sawamura M. Spectrophotometric assay for superoxide dismutase based on the reduction of highly water-soluble tetrazolium salts by xanthine-xanthine oxidase. Bioscience, biotechnology, and biochemistry. 1999;63(3):485-8.
  • 22. Weiss RB. The anthracyclines: will we ever find a better doxorubicin? Seminars in oncology. 1992;19(6):670-86.
  • 23. Injac R, Boskovic M, Perse M, Koprivec-Furlan E, Cerar A, Djordjevic A, et al. Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60 (OH) 24 via suppression of oxidative stress. Pharmacological Reports. 2008;60(5):742.
  • 24. Abdelmeguid NE, Chmaisse HN, Zeinab N. Protective effect of silymarin on cisplatin-induced nephrotoxicity in rats. Pak J Nutr. 2010;9(7):624-36.
  • 25. Thandavarayan RA, Giridharan VV, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, et al. Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/ p53 signaling. PLoS One. 2015;10(3):e0119214.
  • 26. AlAsmari AF, Ali N, Alharbi M, Alqahtani F, Alasmari F, Almoqbel D, et al. Geraniol Ameliorates Doxorubicin-Mediated Kidney Injury through Alteration of Antioxidant Status, Inflammation, and Apoptosis: Potential Roles of NF-κB and Nrf2/Ho-1. Nutrients. 2022;14(8):1620.
  • 27. Robles NR, Ocon J, Gomez CF, Manjon M, Pastor L, Herrera J, et al. Lercanidipine in patients with chronic renal failure: the ZAFRA study. Renal failure. 2005;27(1):73-80.
  • 28. Robles NR, Calvo C, Sobrino J, Espinel E, Esteban R, Mateos L, et al. Lercanidipine valuable effect on urine protein losses: the RED LEVEL study. Current medical research and opinion. 2016;32(sup2):29-34.
  • 29. Li J, Li Q-x, Xie X-f, Ao Y, Tie C-r, Song R-j. Differential roles of dihydropyridine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin-induced renal tubular toxicity in rats. European journal of pharmacology. 2009;620(1-3):97-104.
  • 30. Khan TH, Ganaie MA, Alharthy KM, Madkhali H, Jan BL, Sheikh IA. Naringenin prevents doxorubicin-induced toxicity in kidney tissues by regulating the oxidative and inflammatory insult in Wistar rats. Archives of physiology and biochemistry. 2020;126(4):300-7.
  • 31. Kocahan S, Dogan Z, Erdemli E, Taskin E. Protective effect of quercetin against oxidative stress-induced toxicity associated with doxorubicin and cyclophosphamide in rat kidney and liver tissue. Iranian journal of kidney diseases. 2017;11(2):124.
  • 32. Özgen ZE. Doksorubisin Kardiyotoksisitesinin Oluşumu ve Önlenmesi. Izmir Democracy University Health Sciences Journal. 4(1):1-15.
  • 33. Altinoz E, Oner Z, Elbe H, Uremis N, Uremis M. Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin- induced kidney injury by modulating oxidative stress. Drug and Chemical Toxicology. 2021:1-7.
  • 34. Rachmani R, Levi Z, Zadok BS, Ravid M. Losartan and lercanidipine attenuate low‐density lipoprotein oxidation in patients with hypertension and type 2 diabetes mellitus: A randomized, prospective crossover study. Clinical Pharmacology & Therapeutics. 2002;72(3):302-7.
  • 35. Cominacini L, Pasini AF, Garbin U, Pastorino AM, Davoli A, Nava C, et al. Antioxidant activity of different dihydropyridines. Biochemical and Biophysical Research Communications. 2003;302(4):679-84.
  • 36. Martinez ML, Lopes LF, Coelho EB, Nobre F, Rocha JB, Gerlach RF, et al. Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension. Journal of cardiovascular pharmacology. 2006;47(1):117-22.
  • 37. Taddei S, Virdis A, Ghiadoni L, Versari D, Salvetti G, Magagna A, et al. Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003;41(4):950-5.
  • 38. Gazdikova K, Fojtova A, Ticha L. Kidney manifestations of mitochondrial disorders. Bratislavske Lekarske Listy. 2022;123(9):659-71.
  • 39. Wallace KB, Sardão VA, Oliveira PJ. Mitochondrial determinants of doxorubicin-induced cardiomyopathy. Circulation research. 2020;126(7):926-41.
  • 40. Ali N, AlAsmari AF, Imam F, Ahmed MZ, Alqahtani F, Alharbi M, et al. Protective effect of diosmin against doxorubicin-induced nephrotoxicity. Saudi Journal of Biological Sciences. 2021;28(8):4375-83.
  • 41. Al Seyedan A, Dezfoulian O, Alirezaei M. Satureja khuzistanica Jamzad essential oil prevents doxorubicin-induced apoptosis via extrinsic and intrinsic mitochondrial pathways. Research in Pharmaceutical Sciences. 2020;15(5):481.
  • 42. Elbaz EM, Helmy HS, El-Sahar AE, Saad MA, Sayed RH. Lercanidipine boosts the efficacy of mesenchymal stem cell therapy in 3-NP-induced Huntington's disease model rats via modulation of the calcium/calcineurin/NFATc4 and Wnt/β-catenin signalling pathways. Neurochemistry International. 2019;131:104548.
  • 43. Afsar T, Razak S, Almajwal A, Al-Disi D. Doxorubicin-induced alterations in kidney functioning, oxidative stress, DNA damage, and renal tissue morphology; Improvement by Acacia hydaspica tannin-rich ethyl acetate fraction. Saudi Journal of Biological Sciences. 2020;27(9):2251-60.
  • 44. Rosenthal T, Rosenmann E, Tomassoni D, Amenta F. Effect of lercanidipine on kidney microanatomy in Cohen-Rosenthal diabetic hypertensive rats. Journal of cardiovascular pharmacology and therapeutics. 2007;12(2):145-52.
  • 45. Venu K, Sujitha E, Samreen N, Rao CS, Fathima M, Syed AH, et al. Hepatoprotective agents as calcium channel blockers in paracetamol-induced and alcohol-induced hepatotoxicity models (curative method) in rats. Egyptian Pharmaceutical Journal. 2020;19(4):371.

DOKSORUBİSİN İLE OLUŞTURULAN BÖBREK HASARINDA LERKANİDİPİNİN ANTİOKSİDAN VE ANTİAPOPTOTİK ETKİLERİNİN BCL-2/BAX/SİT C/ CAS-3 YOLAĞI ÜZERİNDEN ARAŞTIRILMASI

Year 2022, Volume: 29 Issue: 4, 671 - 679, 27.12.2022
https://doi.org/10.17343/sdutfd.1198304

Abstract

Amaç
Doksorubisin (Dox) kemoterapide kullanılan antineoplastik
bir ilaçtır. Nefrotoksisite, Dox’un kullanımını
kısıtlayan önemli yan etkilerden biridir. Bir kalsiyum
kanal blokeri olan lerkanidipinin (Ler) antioksidan ve
antiapoptotik özellik gösterdiği bilinmektedir. Çalışmamızda,
sıçanlarda oluşturulan Dox uygulaması ile
tetiklenen böbrek hasarında Ler’in oksidatif stres ve
apoptoz üzerine etkilerini değerlendirmeyi amaçladık.
Gereç ve Yöntem
Yirmi dört adet erişkin erkek sıçan; kontrol, Dox (8.
günde bir kez intraperitoneal 20 mg/kg) ve Dox+Ler
(8. günde bir kez intraperitoneal 20 mg/kg Dox, her
gün oral gavaj ile 2 mg/kg Ler 10 gün boyunca) şeklinde
3 eşit gruba ayrılmıştır. Çalışma sonunda sakrifiye
edilen sıçanların kanlarından kan üre azotu (BUN) ve
kreatinin ile alınan böbrek dokusundan total oksidan
seviyesi (TOS), total antioksidan seviyesi (TAS) ve
süperoksid dismutaz (SOD) enzim aktivitesi ölçülmüştür.
Ayrıca, böbrek dokusunda Bcl-2-ilişkili X proteini
(Bax), B hücreli lenfoma-2 (Bcl-2), sitokrom c (sit
c) ve kaspaz-3 (Cas-3) mRNA ekspresyon düzeyleri
kantitatif gerçek zamanlı polimeraz zincir reaksiyonu
yöntemiyle ölçülmüştür. Ek olarak hematoksilen-eozin
boyama ile böbrekteki histopatolojik değişimler
incelenmiştir.
Bulgular
Çalışmamızda, Dox uygulaması BUN, kreatinin, TOS
ve oksidatif stres indeks seviyelerini yükseltirken,
SOD aktivitesi ve TAS seviyelerini azaltmıştır. Ayrıca
Dox grubunda proapoptotik belirteçlerin (Bax, sit c ve
Cas-3) ekspresyonu artarken antiapoptotik bir faktör
olan Bcl-2’nin ekspresyonu azalmıştır. Histolojik incelemelerde
ise Dox’a bağlı böbrek hasarını gösteren
bulgular gözlenmiştir. Ler uygulaması, böbrekte
Dox’a bağlı tüm değişiklikleri sınırlayarak koruyucu
etkiler göstermiştir.
Sonuç
Çalışmamız Ler’in antioksidan ve antiapoptotik özellikler
göstererek Dox’un neden olduğu böbrek hasarını
önlemede potansiyel bir aday olabileceğini göstermektedir.

References

  • 1. Refaie MM, Amin EF, El-Tahawy NF, Abdelrahman AM. Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats. Journal of toxicology. 2016;2016:9507563.
  • 2. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of pharmacy and pharmacology. 2013;65(2):157-70.
  • 3. Wu Q, Li W, Zhao J, Sun W, Yang Q, Chen C, et al. Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation. Biomedicine & harmacotherapy. 2021;137:111308. 4. Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicology letters. 2019;307:41-8.
  • 5. Özcan O, Erdal H, Çakırca G, Yönden Z. Oksidatif stres ve hücre içi lipit, protein ve DNA yapıları üzerine etkileri. Journal of Clinical and Experimental Investigations. 2015;6(3):331-6.
  • 6. Malarkodi KP, Balachandar AV, Varalakshmi P. The influence of lipoic acid on adriamycin induced nephrotoxicity in rats. Mol Cell Biochem. 2003;247(1-2):15-22.
  • 7. Jha JC, Banal C, Chow BS, Cooper ME, Jandeleit-Dahm K. Diabetes and kidney disease: role of oxidative stress. Antioxidants & redox signaling. 2016;25(12):657-84.
  • 8. Taskin E, Ozdogan K, Kunduz Kindap E, Dursun N. The restoration of kidney mitochondria function by inhibition of angiotensin- II production in rats with acute adriamycin-induced nephrotoxicity. Renal Failure. 2014;36(4):606-12.
  • 9. Atagün G, Zafer E, Gürkanlı İ. Apoptoziste mitokondrinin rolü. Türk Bilimsel Derlemeler Dergisi. 2011(2):9-53.
  • 10. Su Z, Ye J, Qin Z, Ding X. Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro. Scientific reports. 2015;5(1):1-14.
  • 11. Grassi G, Robles NR, Seravalle G, Fici F. Lercanidipine in the management of hypertension: an update. Journal of Pharmacology and Pharmacotherapeutics. 2017;8(4):155-65.
  • 12. Testa R, Leonardi A, Tajana A, Riscassi E, Magliocca R, Sartani A. Lercanidipine (Rec 15/2375): A Novel 1, 4‐Dihydropyridine Calcium Antagonist for Hypertension. Cardiovascular Drug Reviews. 1997;15(3):187-219.
  • 13. Epstein M. Lercanidipine: a novel dihydropyridine calcium-channel blocker. Heart Dis. 2001;3(6):398-407.
  • 14. Bernocchi P, Ceconi C, Cargnoni A, Pedersini P, Boraso A, Curello S, et al. Effects of lercanidipine on Fe2+-induced mitochondrial lipid peroxidation. Journal of Cardiovascular Pharmacology. 1997;29:S63-S72.
  • 15. Vasigar P, Batmanabane M. Anti-inflammatory activity of calcium channel blocker lercanidipine hydrochloride. Journal of Pharmacology and Pharmacotherapeutics. 2013;4(4):238-42.
  • 16. Gupta S, Sharma U, Jagannathan NR, Gupta YK. Neuroprotective effect of lercanidipine in middle cerebral artery occlusion model of stroke in rats. Experimental neurology. 2017;288:25- 37.
  • 17. Ayla S, Seckin I, Tanriverdi G, Cengiz M, Eser M, Soner BC, et al. Doxorubicin induced nephrotoxicity: protective effect of nicotinamide. Int J Cell Biol. 2011;2011:390238.
  • 18. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy. 2016;7(2):27.
  • 19. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.
  • 20. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. 2004;37(4):277-85.
  • 21. Ukeda H, Kawana D, Maeda S, Sawamura M. Spectrophotometric assay for superoxide dismutase based on the reduction of highly water-soluble tetrazolium salts by xanthine-xanthine oxidase. Bioscience, biotechnology, and biochemistry. 1999;63(3):485-8.
  • 22. Weiss RB. The anthracyclines: will we ever find a better doxorubicin? Seminars in oncology. 1992;19(6):670-86.
  • 23. Injac R, Boskovic M, Perse M, Koprivec-Furlan E, Cerar A, Djordjevic A, et al. Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60 (OH) 24 via suppression of oxidative stress. Pharmacological Reports. 2008;60(5):742.
  • 24. Abdelmeguid NE, Chmaisse HN, Zeinab N. Protective effect of silymarin on cisplatin-induced nephrotoxicity in rats. Pak J Nutr. 2010;9(7):624-36.
  • 25. Thandavarayan RA, Giridharan VV, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, et al. Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/ p53 signaling. PLoS One. 2015;10(3):e0119214.
  • 26. AlAsmari AF, Ali N, Alharbi M, Alqahtani F, Alasmari F, Almoqbel D, et al. Geraniol Ameliorates Doxorubicin-Mediated Kidney Injury through Alteration of Antioxidant Status, Inflammation, and Apoptosis: Potential Roles of NF-κB and Nrf2/Ho-1. Nutrients. 2022;14(8):1620.
  • 27. Robles NR, Ocon J, Gomez CF, Manjon M, Pastor L, Herrera J, et al. Lercanidipine in patients with chronic renal failure: the ZAFRA study. Renal failure. 2005;27(1):73-80.
  • 28. Robles NR, Calvo C, Sobrino J, Espinel E, Esteban R, Mateos L, et al. Lercanidipine valuable effect on urine protein losses: the RED LEVEL study. Current medical research and opinion. 2016;32(sup2):29-34.
  • 29. Li J, Li Q-x, Xie X-f, Ao Y, Tie C-r, Song R-j. Differential roles of dihydropyridine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin-induced renal tubular toxicity in rats. European journal of pharmacology. 2009;620(1-3):97-104.
  • 30. Khan TH, Ganaie MA, Alharthy KM, Madkhali H, Jan BL, Sheikh IA. Naringenin prevents doxorubicin-induced toxicity in kidney tissues by regulating the oxidative and inflammatory insult in Wistar rats. Archives of physiology and biochemistry. 2020;126(4):300-7.
  • 31. Kocahan S, Dogan Z, Erdemli E, Taskin E. Protective effect of quercetin against oxidative stress-induced toxicity associated with doxorubicin and cyclophosphamide in rat kidney and liver tissue. Iranian journal of kidney diseases. 2017;11(2):124.
  • 32. Özgen ZE. Doksorubisin Kardiyotoksisitesinin Oluşumu ve Önlenmesi. Izmir Democracy University Health Sciences Journal. 4(1):1-15.
  • 33. Altinoz E, Oner Z, Elbe H, Uremis N, Uremis M. Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin- induced kidney injury by modulating oxidative stress. Drug and Chemical Toxicology. 2021:1-7.
  • 34. Rachmani R, Levi Z, Zadok BS, Ravid M. Losartan and lercanidipine attenuate low‐density lipoprotein oxidation in patients with hypertension and type 2 diabetes mellitus: A randomized, prospective crossover study. Clinical Pharmacology & Therapeutics. 2002;72(3):302-7.
  • 35. Cominacini L, Pasini AF, Garbin U, Pastorino AM, Davoli A, Nava C, et al. Antioxidant activity of different dihydropyridines. Biochemical and Biophysical Research Communications. 2003;302(4):679-84.
  • 36. Martinez ML, Lopes LF, Coelho EB, Nobre F, Rocha JB, Gerlach RF, et al. Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension. Journal of cardiovascular pharmacology. 2006;47(1):117-22.
  • 37. Taddei S, Virdis A, Ghiadoni L, Versari D, Salvetti G, Magagna A, et al. Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003;41(4):950-5.
  • 38. Gazdikova K, Fojtova A, Ticha L. Kidney manifestations of mitochondrial disorders. Bratislavske Lekarske Listy. 2022;123(9):659-71.
  • 39. Wallace KB, Sardão VA, Oliveira PJ. Mitochondrial determinants of doxorubicin-induced cardiomyopathy. Circulation research. 2020;126(7):926-41.
  • 40. Ali N, AlAsmari AF, Imam F, Ahmed MZ, Alqahtani F, Alharbi M, et al. Protective effect of diosmin against doxorubicin-induced nephrotoxicity. Saudi Journal of Biological Sciences. 2021;28(8):4375-83.
  • 41. Al Seyedan A, Dezfoulian O, Alirezaei M. Satureja khuzistanica Jamzad essential oil prevents doxorubicin-induced apoptosis via extrinsic and intrinsic mitochondrial pathways. Research in Pharmaceutical Sciences. 2020;15(5):481.
  • 42. Elbaz EM, Helmy HS, El-Sahar AE, Saad MA, Sayed RH. Lercanidipine boosts the efficacy of mesenchymal stem cell therapy in 3-NP-induced Huntington's disease model rats via modulation of the calcium/calcineurin/NFATc4 and Wnt/β-catenin signalling pathways. Neurochemistry International. 2019;131:104548.
  • 43. Afsar T, Razak S, Almajwal A, Al-Disi D. Doxorubicin-induced alterations in kidney functioning, oxidative stress, DNA damage, and renal tissue morphology; Improvement by Acacia hydaspica tannin-rich ethyl acetate fraction. Saudi Journal of Biological Sciences. 2020;27(9):2251-60.
  • 44. Rosenthal T, Rosenmann E, Tomassoni D, Amenta F. Effect of lercanidipine on kidney microanatomy in Cohen-Rosenthal diabetic hypertensive rats. Journal of cardiovascular pharmacology and therapeutics. 2007;12(2):145-52.
  • 45. Venu K, Sujitha E, Samreen N, Rao CS, Fathima M, Syed AH, et al. Hepatoprotective agents as calcium channel blockers in paracetamol-induced and alcohol-induced hepatotoxicity models (curative method) in rats. Egyptian Pharmaceutical Journal. 2020;19(4):371.
There are 44 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Articles
Authors

İlter İlhan 0000-0003-3739-9580

Halil Aşcı 0000-0002-1545-035X

Mehmer Abdulkadir Sevük 0000-0003-3875-9365

Orhan Berk İmeci 0000-0002-3850-0137

Adem Milletsever 0000-0002-3614-7798

Okan Sancer 0000-0001-7935-5004

Publication Date December 27, 2022
Submission Date November 2, 2022
Acceptance Date December 6, 2022
Published in Issue Year 2022 Volume: 29 Issue: 4

Cite

Vancouver İlhan İ, Aşcı H, Sevük MA, İmeci OB, Milletsever A, Sancer O. DOKSORUBİSİN İLE OLUŞTURULAN BÖBREK HASARINDA LERKANİDİPİNİN ANTİOKSİDAN VE ANTİAPOPTOTİK ETKİLERİNİN BCL-2/BAX/SİT C/ CAS-3 YOLAĞI ÜZERİNDEN ARAŞTIRILMASI. Med J SDU. 2022;29(4):671-9.

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