Sülforafanın ratlarda asetaminofenin-indüklediği nefrotoksisitede sistatin-c düzeylerine etkisi

Abstract

Amaç: Canlıların kimyasallara ve ilaçlara maruziyeti sıklıkla karaciğer ve böbrek toksisitesi ile sonuçlanır. Toplum ve hastane kaynaklı böbrek hastalıklarının önemli ve büyük bir kısmını ilaçlar oluşturmaktadır. Çalışmamızda, asetaminofen (APAP) ile ratlarda indüklenen nefrotoksisitede sülforafanın (SFN) sistatin-C düzeyleri ve lipid peroksidasyonu üzerine olan etkilerinin araştırılması amaçlanmıştır. Yöntemler: 36 Sprague-Dawley sıçan her bir grup eşit hayvan içerecek şekilde dört gruba ayrıldı. Gruplarımız, kontrol grubu, SFN grubu, APAP grubu ve APAP+SFN grubundan oluşmaktadır. SFN ve APAP+SFN grubundaki sıçanlara tedavi için üç gün süresince 500 μg/kg dozunda SFN oral gavaj yoluyla verildi. APAP ve APAP+SFN grubundaki sıçanlara hepatotoksisite oluşturmak için APAP sıcak salin içerisinde çözüldü ve çalışmanın son gününde 1g/kg olacak şekilde tek doz oral gavaj yoluyla uygulandı. APAP+SFN grubunda, APAP uygulaması SFN uygulamasından üç saat sonra yapıldı. APAP uygulamasından 24 saat sonra sıçanlar sakrifiye edildi. Bulgular: APAP uygulamasının serum üre, kreatinin, LDH ve BUN düzeylerini kontrol grubuna göre anlamlı derecede arttığı gözlemlenmiştir (p<0.001). SFN uygulamasının sistatin C düzeylerini ve lipid peroksidasyonunu APAP grubuna göre azalttığı gözlemlenmiştir (p<0.05). Sonuç: Sülforafanın, asetaminofen kaynaklı nefrotoksisitede tedavi protokolüne eklenmesinin yarar sağlayacağını düşünmekteyiz. Böbrek hastalıklarında önemli bir rol oynayan sistatin C’nin bir biyomarker olarak rutine girebilmesi için çeşitli çalışmalara ihtiyaç vardır

Keywords

• Asetaminofen, Sistatin C, Lipid peroksidasyonu, Nefrotoksisite

The effect of sulforaphane on the levels of serum cystatin-c in acetaminophen-induced nephrotoxicity in rats

Abstract

Objective: The exposure of living creatures to drugs and chemicals often results in toxicity of liver and kidney. Drugs constitute an important and big part of the commu­nity and hospital-acquired kidney diseases. In this study, we investigated the effect of sulforaphane (SFN) on the levels of cystatin-C and lipid peroxidation on acetamino­phen (APAP)- induced nephrotoxicity in rats. Methods: Thirty-six Sprague-Dawley rats were separat­ed equally into four experimental groups: control group, SFN group, APAP group, and APAP + SFN group. In the experimental treatment groups APAP was administered oral gavage at 1 g/kg 3 h after SFN treatment in last day and, in the APAP + SFN group, SFN was administered oral gavage at a dose of 500 μg/kg exactly for three days. Rats were euthanized and sacrificed 24 h after APAP ad­ministration. Results: APAP administration showed to significant in­crease in serum BUN, creatinine, urea and LDH concen­trations as compared to the control datas indicating the induction of severe nephrotoxicity (p<0.001). SFN treat­ment significantly decreased the cystatin-C levels and lipid peroxidation compared to APAP group (p<0.05). Conclusion: The present study demonstrate that the at­tachment of SFN to the nephrotoxicity treatment protocol will be beneficial and further studies should be conducted for cystatin C which plays an important role in kidney tox­icity and disease to be routinized as a biomarker.

Keywords

• Acetaminophen, Cystatin-C, Lipid peroxidation, Nephrotoxicity

References

1. 1. Parlakpinar H, Orum MH, Acet A. Free Oxygen Radicals in Drug-Induced Nephrotoxicity. Fırat Univ Med Health Sci 2013;27:51-6.
2. 2. Sohn SH, Lee EY, Lee JH, et al. Screening of herbal medicines for recovery of acetaminophen-induced nephrotoxicity. Environ Toxicol Pharmacol 2009;27:225-30.
3. 3. Yıldızhan E, Kutlucan A, Güngör A, et al. Subconjonctival hemorrhage secondary to use of diclofenac and paracetamol for suicidal attempt. Dicle Med J 2011;38:79-82.
4. 4. Bessems JG, Vermeulen NP. Paracetamol (acetaminophen)- induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit Rev Toxicol 2001;31:55-138.
5. 5. Fouad AA, Yacoubi MT, El-Bidawy MH. Therapeutic potential of hemin in acetaminophen nephrotoxicity in rats. Environ Toxicol Pharmacol 2009;27:277-82.
6. 6. Ozdemir AV, Akagac A, Mızrak ES. The Importance of Cystatin C in the Early Diagnosis of Renal Dysfunction in Renal Function Disorders. Turk J Biochem 2015;13:51-8.
7. 7. Miklaszewska M, Pietrzyk JA, Zachwieja K, et al. Early laboratory markers of acute renal failure. Przegl Lek 2006;63:81-4.
8. 8. Brguljan PM, Cimerman N. Human Cystatin C. Turk J Biochem 2007;32:95–103.

9. 9. Newman D. More on cystatin C. Clin Chem 1999;45:718-19.
10. 10. Yildiz N, Caliskan S, Kabasakal L, et al. Cystatin C: can it be more reliable marker for estimation of glomerular filtration rate in children with reduced renal function? Turk Arch Ped 2011;46:118-23.
11. 11. Filler G, Priem F, Lepage N, Jung K. Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children. Clin Chem 2002;48:729-36.
12. 12. Randers E, Erlandsen EJ. Serum cystatin C as an endogen marker of renal functions – a review. Clin Chem Lab Med 1999;37:389-95.
13. 13. Yapar K, Kart A, Karapehlivan M, et al. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice. Exp Toxicol Pathol 2007;59:121-8.
14. 14. Ghosh A, Sil PC. Anti-oxidative effect of a protein from Cajanus indicus L. against acetaminophen-induced hepato– nephro toxicity. J Biochem Mol Biol 2007;40:1039-49.
15. 15. Guerrero-Beltrán CE, Calderón-Oliver M, Pedraza-Chaverri J, Chirino-Irasema Y. Protective effect of sulforaphane against oxidative stress: Recent advances. Exp Toxicol Pathol 2012;64:503-8.
16. 16. Yoon HY, Kang NI, Lee HK, et al. Sulforaphane protects kidneys against ischemia–reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme. Biochem Pharmacol 2008;75:2214-23.
17. 17. Zhao HD, Zhang F, Shen G, Tian X. Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway. World J Gastroenterol 2010;16:3002-10.
18. 18. Naggayi M, Mukiibi N, Iliya E. The protective effects of aqueous extract of Carica papaya seeds in paracetamol induced nephrotoxicity in male wistar rats. Afr Health Sci 2015;15:598-605.
19. 19. Gaona-Gaona L, Molina-Jijón E, Tapia E, et al. Protective effect of sulforaphane pretreatment against cisplatininduced liver and mitochondrial oxidant damage in rats. Toxicology 2011;286:20-7.
20. 20. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
21. 21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
22. 22. Palani S, Raja S, Kumar RP, Senthil-Kumar B. Therapeutic efficacy of Pimpinella tirupatiensis (Apiaceae) on acetaminophen induced nephrotoxicity and oxidative stress in male albino rats. Int J Pharm Tech Res 2009;1:925-34.
23. 23. Ozdemir AV, Akagac A, Mizrak ES. The Importance of Cystatin C in the Early Diagnosis of Renal Dysfunction in Renal Function Disorders. Turk J Biochem 2015;13:51-8.
24. 24. Pradhan S, Mandal S, Roy S, et al. Attenuation of uremia by orally feeding alpha-lipoic acid on acetaminophen induced uremic rats. Saudi Pharm J 2013;21:187-92.
25. 25. Cekmen M, Ilbey YO, Ozbek E, et al. Curcumin prevents oxidative renal damage induced by acetaminophen in rats. Food Chem Toxicol 2009;47:1480-4.
26. 26. Erdinç M, Erdinç L, Nergiz Y, Kelle İ. The Effects of Nifedipine on Renal Perfusion Pressure and Kidney During Cisplatin-Induced Nephrotoxicity in Rats. Dicle Med J 2007;34:248-53.
27. 27. Adeneye AA, Benebo AS. Protective effect of the aqueous leaf and seed extract of Phyllanthus amarus on gentamicin and acetaminophen-induced nephrotoxic rats. J Ethnopharmacol 2008;118:318-23.
28. 28. Ushaliran RT, Mohana LS, Ashok-Kumar CK, et al. Protective effect of abutilon indicum L. (Malvaceae) against acetaminophen induced nephrotoxicity in rats. Innovare J Life Sci 2013;1:40-3.
29. 29. Ozsoy N, Okyar A, Arda-Pirinccin P, et al. Evaluation of Smilax excelsa L. Use in Experimentally Induced Nephrotoxicity. Kafkas Univ Vet Fak Derg 2013;19:807-14.
30. 30. Naggayi M, Mukiibi N, Iliya E. The protective effects of aqueous extract of Carica papaya seeds in paracetamol induced nephrotoxicity in male wistar rats. Afr Health Sci 2015;15:598-605.
31. 31. Nielsen F, Mikkelsen BB, Nielsen JB, et al. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 1997;43:1209-14.
32. 32. Abdul-Hamid Z, Budin SB, Wen-Jie N, et al. Nephroprotective effects of Zingiber zerumbet Smith ethyl acetate extract against paracetamol-induced nephrotoxicity and oxidative stress in rats. J Zhejiang Univ Sci B 2012;13:176-85.
33. 33. Aycan IO, Tokgoz O, Tufek A, et al. The use of thymoquinone in nephrotoxicity related to acetaminophen. Int J Surg 2015;13: 33-7.
34. 34. Guerrero-Beltrán CE, Calderón-Oliver M, Tapia E, et al. Sulforaphane protects against cisplatin-induced nephrotoxicity. Toxicol Lett 2010;192:278-85.
35. 35. Demirtas S, Bozbas A, Akbay A. Diagnostic value of serum cystatin C for evaluation of hepatorenal syndrome. Clin Chim Acta 2001;311:81-9.
36. 36. Herget-Rosenthal S, Marggraf G, Hüsing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004; 66:1115-22.
37. 37. Si YN, Bao HG, Xu L, et al. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney. Eur Rev Med Pharmacol Sci 2014;18:1843-51.
38. 38. Shokeir AA, Barakat N, Hussein AM, et al. Activation of Nrf2 by ischemic preconditioning and sulforaphane in renal ischemia/reperfusion injury: a comparative experimental study. Physiol Res 2015;64:313-23.
39. 39. Negrette-Guzmán M, Huerta-Yepez S, Medina-Campos ON, et al. Sulforaphane attenuates gentamicin-induced nephrotoxicity: role of mitochondrial protection. Evid Based Complement Alternat Med 2013;2013:135314.
40. 40. Abdel-Zaher AO, Abdel-Rahman MM, Hafez MM, Omran FM. Role of nitric oxide and reduced glutathione in the protective effects of aminoguanidine, gadolinium chloride and oleanolic acid against acetaminophen-induced hepatic and renal damage. Toxicology 2007;234:124-34.