Yıl: 2007 Cilt: 34 Sayı: 4 Sayfa Aralığı: 248 - 253 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats

Öz:
Sisplatin kanser kemoterapisinde solid tümörlere karşı oldukça etkin ve geniş kullanıma sahip olan bir kemoterapötik ajandır. Nefrotoksisite en önemli doz-kısıtlayıcı yan etkisidir. Renal hemodinamide değişikliklerle sonuçlanan cisplatin nefrotoksisitesinde oksidatif stres gibi farklı mekanizmaların rol oynadığı bilinmektedir. Bu çalışmada tek doz sisplatin ile nefrotoksisite oluşturulan erkek wistar albino sıçanlarda bir dihidropiridin grubu kalsiyum antagonisti olan nifedipinin renal perfüzyon basıncı ve böbrekler üzerine etkileri araştırıldı. Erkek wistar albino sıçanlar üç gruba ayrıldı (n=8). 1-Kontrol grubu: (1ml salin, i.p) 2-Sisplatin grubu: Tek doz sisplatin (5 mg/kg, i.p). 3-Tek doz sisplatin + 5 gün süre ile Nifedipin (2 mg/kg/gün, i.p). İlaç grupları kontrol grubu ile karşılaştırıldığında perfüzyon basınçları, serum üre, kreatinin ve doku MDA düzeyleri sisplatin grubunda anlamlı olarak yüksek bulundu (p<0.001). Histopatolojik olarak da kontrol grubu ile karşılaştırıldığında, sisplatin grubunda yaygın tubuler nekroz ve tubuler dilatasyon olduğu görüldü. Sisplatin + nifedipin grubu sisplatin grubu ile karşılaştırıldığında perfüzyon basınçları, serum üre, kreatinin ve doku MDA düzeyleri sisplatin grubundan anlamlı olarak daha düşük bulundu (p<0.001) ve histopatolojik olarak daha az tubuler nekroz ve dilatasyon olduğu görüldü. Sonuç olarak nifedipinin sisplatin nefrotoksisitesine karşı koruyucu etkili olduğu görüldü. Biz bu etkiden kısmen, sisplatin nefrotoksisitesi sırasında değişen renal hemodinamikler üzerine nifedipinin yararlı etkilerinin sorumlu olduğunu düşünüyoruz.
Anahtar Kelime: Nifedipin Böbrek Erkek Perfüzyon Sisplatin Sıçan, Wistar

Konular: Cerrahi

Sıçanlarda sisplatin ile oluşturulan nefrotoksisitede nifedipin’in renal perfüzyon basıncı ve böbrek üzerine etkileri

Öz:
Cisplatin is one of the most effective cancer chemotherapeutic agent used against various solid tumors. Nephrotoxicity is one of the major dose-limiting side effects of cisplatin. It has been known that different mechanisms as oxidative stress may play an important role in cisplatin induced nephrotoxicity resulted with changes in renal haemodynamics. This study was performed to investigate the effect of nifedipine &#8211;one of the dihydropyridine calcium antagonist on changes in renal perfusion pressures and kidneys of rats with cisplatin nephrotoxicity. Male wistar albino rats were divided into 3 groups (n=8):1-Control group(1 ml saline. i.p) 2-Cisplatin group (a single dose of cisplatin (5 mg/kg, i.p) 3- A single dose of cisplatin (5 mg/kg, i.p) + Nifedipine (2 mg/kg/day, i.p) for five days. When those pre-treated groups compared with control group, perfusion pressures, serum urea and creatinine levels and tissue MDA levels were found significantly higher in cisplatin group (p<0.001). Histopathological examination showed widespread tubular necrosis and dilatation in cisplatin-treated group versus other groups. In cisplatin + nifedipine pretreated group, perfusion pressures, serum urea and creatinine levels and tissue MDA levels found significantly lower than cisplatin group (p<0. 001) and less tubular dilatation and necrosis was observed. As a result it was demonstrated that Nifedipine has protective effects against cisplatin nephrotoxicity. We suggest that this is partly provided by the beneficial effects of nifedipine on altered renal haemodynamics during cisplatin nephrotoxicity.
Anahtar Kelime: Male Perfusion Cisplatin Rats, Wistar Nifedipine Kidney

Konular: Cerrahi
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Livingston RB: Cisplatin in the treatment of solid tumors:effect of dose and schedule. J Natl Cancer Inst 1989; 81: 724- 725.
  • 2. Meyer KB, Madias NE: Cisplatin nephrotoxicity. Miner Electrolyte Metab 1994; 20: 201-213.
  • 3. Weiner MW and Jacobs C: Mechanism of cisplatin nephrotoxicity. Fed. Proc 1983; 42: 2974-2978.
  • 4. Hanneman J, Baumann K: Cisplatininduced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex:Different effects of antioxidants and radical scavengers. Toxicology 1988; 51: 119-132.
  • 5. Matsushima H, Yonemura K, Ohishi K, Hishida A: The role of oxygen free radicals in cisplatin-induced acute renal failure in rats. J Lab Clin Med 1998; 131: 518-526.
  • 6. Ali BH and Moundhri MS: Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: A review of some recent research. Food Chem Toxicol 2006; 44: 1173-1183.
  • 7. Blachley JD, Hill JB: Renal and electrolyte disturbances associated with cisplatin. Ann Intern Med 1981; 95; 628-632.
  • 8. Leibbrandt ME, Wolfgang GH, Metz AL, Ozobia AA, Haskins JR: Critical subcellular targets of cisplatin and related platinum analogs in rat renal proximal tubule cells. Kidney Int 1995; 48: 761-770.
  • 9. Tobe S: Update on calcium antagonists and the kidney. Curr Opin Nephrol Hypertens 2003; 12: 309-315.
  • 10. Bakris GL, Weir MR, Secic M, Campbell B, Weis-McNulty A: Differential effects of calcium antagonist subclasses on markers of nephropathy progression. Kidney Int 2004; 65: 1991-2002.
  • 11. Ohkawa H, Oshishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem 1979; 95: 351-358.
  • 12. Sugihara K and Gemba M: Modification of cisplatin toxicity by antioxidants. Jpn J Pharmacol 1986; 40: 353- 355.
  • 13. Slater TF: Free radical mechanisms in tissue injury. Biochem J 1984; 222: 1-15.
  • 14. Commandeur JN and Vermeulen NP: Molecular and biochemical mechanism of chemically induced nephrotoxicity: a review. Chem Res Toxicol 1990; 3: 171-194.
  • 15. Sean Eardley K and Cockwell P: Macrofages and progressive tubulointerstitial disease. Kidney Int 2005; 68: 437-455.
  • 16. Taguchi T, Nazneen A, Ruhul-Abid M, Razzaque MS: Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol 2005; 148: 107-121.
  • 17. Chander V and Chopra K: Nifedipine attenuates changes in nitric oxide levels, renal oxidative stress and nephrotoxicity induced by cyclosporine. Renal Fail 2005; 27: 441-450.
  • 18. Darlametsos IE, Papanikolaou EN, Varonos DD: Effect of nifedipine in cyclosporine-induced nephrotoxicity in rats:roles of the thromboxane and endothelin systems. Prostaglandins Essent Fatty Acids 2000; 63: 263-269.
APA ERDİNÇ M, Erdinç L, NERGİZ Y, KELLE İ (2007). The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. , 248 - 253.
Chicago ERDİNÇ Meral,Erdinç Levent,NERGİZ Yusuf,KELLE İlker The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. (2007): 248 - 253.
MLA ERDİNÇ Meral,Erdinç Levent,NERGİZ Yusuf,KELLE İlker The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. , 2007, ss.248 - 253.
AMA ERDİNÇ M,Erdinç L,NERGİZ Y,KELLE İ The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. . 2007; 248 - 253.
Vancouver ERDİNÇ M,Erdinç L,NERGİZ Y,KELLE İ The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. . 2007; 248 - 253.
IEEE ERDİNÇ M,Erdinç L,NERGİZ Y,KELLE İ "The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats." , ss.248 - 253, 2007.
ISNAD ERDİNÇ, Meral vd. "The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats". (2007), 248-253.
APA ERDİNÇ M, Erdinç L, NERGİZ Y, KELLE İ (2007). The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. Dicle Tıp Dergisi, 34(4), 248 - 253.
Chicago ERDİNÇ Meral,Erdinç Levent,NERGİZ Yusuf,KELLE İlker The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. Dicle Tıp Dergisi 34, no.4 (2007): 248 - 253.
MLA ERDİNÇ Meral,Erdinç Levent,NERGİZ Yusuf,KELLE İlker The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. Dicle Tıp Dergisi, vol.34, no.4, 2007, ss.248 - 253.
AMA ERDİNÇ M,Erdinç L,NERGİZ Y,KELLE İ The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. Dicle Tıp Dergisi. 2007; 34(4): 248 - 253.
Vancouver ERDİNÇ M,Erdinç L,NERGİZ Y,KELLE İ The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats. Dicle Tıp Dergisi. 2007; 34(4): 248 - 253.
IEEE ERDİNÇ M,Erdinç L,NERGİZ Y,KELLE İ "The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats." Dicle Tıp Dergisi, 34, ss.248 - 253, 2007.
ISNAD ERDİNÇ, Meral vd. "The effects of nifedipine on renal perfusion pressure and kidney during cisplatin-induced nephrotoxicity in rats". Dicle Tıp Dergisi 34/4 (2007), 248-253.