Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C.
BACKGROUND
The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity.


METHODS
Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation.


RESULTS
In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone.


CONCLUSIONS
Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.
a Department of Nuclear Medicine , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Yavuz Sami
YS
Salihoglu
a Department of Nuclear Medicine , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Tarik
T
Elri
b Department of Histology and Embryology , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Kanat
K
Gulle
c Department of Medical Biochemistry , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Murat
M
Can
a Department of Nuclear Medicine , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Mustafa
M
Aras
d Department of Physiology , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Hale Sayan
HS
Ozacmak
a Department of Nuclear Medicine , School of Medicine, Bulent Ecevit University , Zonguldak , Turkey.
Mehmet
M
Cabuk
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002945:Cisplatin / Q000633:toxicity; D055316:Cystatin C / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000494:pharmacology*
D055316:Cystatin C; D019275:Radiopharmaceuticals; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D000376:Agmatine; D002945:Cisplatin
99mTc-DMSA; Agmatine; cisplatin; cystatin C; nephrotoxicity; scintigraphy