Efficacy of prophylactic calcium dobesilate in renal ischemia-reperfusion injury in rats

Yıl 2020, , 169 - 174, 12.07.2020

Ali Akkoç , Ahmet Metin

https://doi.org/10.30565/medalanya.643852

Öz

Aim: In this study, the objective was to investigate the protective effect of calcium dobesilate, which has antioxidant and anti-inflammatory properties, on the experimental renal ischemia-reperfusion injury (IRI). 

Methods: Twenty-four male Wistar-Albino rats were divided into three groups: Sham group (Group 1), ischemia-reperfusion group (Group 2), and treatment group (Group 3). Before the ischemia-reperfusion procedure, rats in Group 3 received calcium dobesilate through gavage (100mg/kg/day) for 10 days. Groups other than the sham group underwent ischemia for 45 minutes and reperfusion for 24 hours. Plasma urea and creatinine levels, erythrocyte superoxide dismutase and glutathione peroxidase enzyme activity levels were measured. In addition, histopathological changes that may be related to ischemia-reperfusion injury in the renal tissue, were investigated.

Results: The median glutathione peroxidase and superoxide dismutase enzyme levels were higher in Group 2 compared to Groups 1 and 3. However, the differences were not statistically significant. The creatine levels were statistically lower in Group 3 compared to Group 1 and Group 2. The median urea levels were lower in Group 3 than in Group 1 and Group 2, but the differences were not statistically significant. The histopathological examination showed that parameters such as cellular necrosis, flattened tubular epithelial cells, cytoplasmic vacuolization, tubular lumen obstruction, and chronic inflammation, which are indicators of the ischemia-reperfusion injury, were statistically less common in the treatment group compared to the control group. 

Conclusion: Our study demonstrated that prophylactic calcium dobesilate had a protective effect on ischemia-reperfusion injury. 

Anahtar Kelimeler

Renal, ischemia-reperfusion, calcium dobesilate, prophylactic

Ratlarda böbrek iskemi-reperfüzyon hasarında proflaktik kalsiyum dobesilatın etkinliği

Öz

Amaç: Çalışmamızda, antioksidan ve antienflamatuvar özellikleri olduğu bilinen, kalsiyum dobesilatın deneysel böbrek iskemi-reperfüzyon hasarı (IRI) üzerindeki koruyucu etkisini araştırmayı amaçladık.

Yöntemler: 24 adet erkek Wistar-Albino rat üç gruba ayrıldı; sham grubu (grup 1), iskemi-reperfüzyon grubu (grup 2) ve tedavi grubu (grup 3). İskemi-reperfüzyon işlemi öncesi Grup 3’e 10 gün boyunca 100 mg/kg/gün kalsiyum dobesilat gavaj yolu ile verildi. Sham grubu haricindeki gruplara 45 dakika iskemi ve 24 saat reperfüzyon uygulandı. Plazma üre ve kreatinin düzeyleri, eritrosit süperoksit dismutaz ve glutatyon peroksidaz enzim aktivite düzeyleri çalışıldı. Ayrıca böbrek dokusundaki iskemi-reperfüzyon hasırına ait olabilecek histopatolojik değişiklikler incelendi.

Bulgular: Grup 2’de ortanca glutatyon peroksidaz ve süperoksit dismutaz enzim düzeyleri Grup 1 ve Grup 3’den daha yüksekti, ancak istatistiksel anlamlı değildi. Grup 3’de kreatinin düzeyleri Grup 1 ve Grup 2’den istatistiksel olarak anlamlı derecede daha düşüktü. Ortanca üre değerleri Grup 3’de Grup 1 ve Grup 2’den daha düşüktü ancak istatistiksel olarak anlamlı değildi. Histopatolojik incelemede; kontrol grubu ile kıyaslandığında tedavi grubunda, hücre nekrozu, tübüler epitelyal hücre düzleşmesi, sitoplazmik vakuolizasyon, tübüler lümen obstrüksiyonu ve kronik inflamasyon gibi iskemi-reperfüzyon hasarının göstergesi olan bu parametrelerin istatistiksel olarak anlamlı derecede daha az olduğu gözlendi. 

Sonuç: Çalışmamız, proflaktik kalsiyum dobesilatın böbrek iskemi-reperfüzyon hasarında koruyucu etkilerinin olduğunu göstermiştir.

Anahtar Kelimeler

Renal, iskemi-reperfüzyon, kalsiyum dobesilat, proflaktik

Kaynakça

• 1. Ozer Sehirli A, Sener G, Ercan F. Protective effects of pycnogenol against ischemia reperfusion-induced oxidative renal injury in rats. Ren Fail. 2009;31(8):690–7. DOI: 10.3109/08860220903085971
• 2. Eraslan E, Tanyeli A, Polat E, Polat E. 8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury. J Cell Physiol. 2019;234(4):4572-81. DOI: 10.1002/jcp.27236
• 3. Çakır M, Tekin S, Taşlıdere A, Çakan P, Düzova H, Gül CC. Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury. J Cell Biochem. 2019;120(3):3822-32. DOI: 10.1002/jcb.27664
• 4. Aktoz T, Aydogdu N, Alagol B, Yalcin O, Huseyinova G, Atakan IH. The protective effects of melatonin and vitamin E against renal ischemia-reperfusion injury in rats. Ren Fail. 2007;29(5):535-42. DOI: 10.1080/08860220701391738
• 5. Bonavia A, Singbartl K. A review of the role of immune cells in acute kidney injury. Pediatr Nephrol. 2018;33(10):1629-39. DOI: 10.1007/s00467-017-3774-5
• 6. Panah F, Ghorbanihaghjo A, Argani H, Asadi Zarmehri M, Nazari Soltan Ahmad S. Ischemic acute kidney injury and klotho in renal transplantation. Clin Biochem. 2018;55:3-8. DOI: 10.1016/j.clinbiochem.2018.03.022
• 7. Allain H, Ramelet AA, Polard E, Bentué-Ferrer D. Safety of calcium dobesilate in chronic venous disease, diabetic retinopathy and haemorrhoids. Drug Saf. 2004;27(9):649-60. DOI: 10.2165/00002018-200427090-00003
• 8. Priollet P, Boisseau MR. Drugs for veno-lymphaticinsufficiency. Rev Prat. 2000;50(11):1195-8. PMID: 11008499
• 9. Paller MS, Hoidal JR, Ferris TF. Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest. 1984;74(4):1156-64. DOI: 10.1172/JCI111524
• 10. Hsu CY, McCulloch CE, Fan D, Ordoñez JD, Chertow GM, Go AS. Community-based incidence of acute renal failure. Kidney Int. 2007;72(2):208-12. DOI: 10.1038/sj.ki.5002297
• 11. Cakir M, Polat A, Tekin S, Vardi N, Taslidere E, Rumeysa Duran Z, et al. The effect of dexmedetomidine against oxidative and tubular damage induced by renal ischemia reperfusion in rats. Ren Fail. 2015;37(4):704-8. DOI: 10.3109/0886022X.2015.1011550
• 12. Klausner JM, Paterson IS, Goldman G, Kobzik L, Rodzen C, Lawrence R, et al. Postischemic renal injury is mediated by neutrophils and leukotrienes. Am J Physiol. 1989;256(5 Pt 2):F794-802. DOI: 10.1152/ajprenal.1989.256.5.F794
• 13. Hannaert P, Brunet J, Farine JC, Garay RP. Antioxidant-Angioprotective Actions of Calcium Dobesilate in Diabetic Rats. Int J Angiol. 1999;8(5):2-4. DOI: 10.1007/bf01619841
• 14. Brunet J, Farine JC, Garay RP, Hannaert P. In vitro antioxidant properties of calcium dobesilate. Fundam Clin Pharmacol. 1998;12(2):205-12. DOI: 10.1111/j.1472-8206.1998.tb00943.x
• 15. Suschek C, Kolb H, Kolb-Bachofen V. Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells. Br J Pharmacol. 1997;122(7):1502-8. DOI: 10.1038/sj.bjp.0701512
• 16. Falkay G, Kovács L. Calcium dobesilate (Doxium) as a prostaglandin synthetase inhibitor in pregnant human myometrium in vitro. Experientia. 198415;40(2):190-1. DOI: 10.1007/bf01963593
• 17. Ernst E, Marshall M. Improvement of reduced erythrocyte flexibility through calcium dobesilate. Results of a pilot study. MMW Munch Med Wochenschr. 1984;126(5):125-6. PMID: 6423981
• 18. Cihan Ozbek I, Arslan C, Cantürk E, Süzer O. The effects of calcium dobesilate on the mechanical function of rat hearts. J Cardiovasc Surg. 2009;50(3):395-401. PMID: 19543197
• 19. Iskesen I, Saribulbul O, Cerrahoglu M, Onur E, Tekin C, Sirin H. Cardioprotective effect of calcium dobesilate during open-heart surgery. Acta Cardiol. 2006;61(1):69-74. DOI: 10.2143/AC.61.1.2005142
• 20. Rota R, Chiavaroli C, Garay RP, Hannaert P. Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in streptozotocin-diabetic rats. Eur J Pharmacol. 2004;495(2-3):217-24. DOI: 10.1016/j.ejphar.2004.05.019
• 21. Szabo ME, Haines D, Garay E, Chiavaroli C, Farine JC, Hannaert P, et al. Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina. Eur J Pharmacol. 2001;428(2):277-86. DOI: 10.1016/s0014-2999(01)01196-7
• 22. Piller NB. Assessment of the anti-inflammatory action of calcium dobesilate. Effect on macrophages attaching to subcutaneously implanted coverslips in guinea pigs. Arzneimittelforschung. 1990;40(6):698-700. PMID: 2397006