Effect of free creatine therapy on cisplatin-induced renal damage.
Abstract Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n=20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin+creatine monohydrate (n=20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n=20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p<0.05). In group II, there was a slight decrease in body weight at same days (p=0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p<0.05). Although creatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.
Pediatric Nephrology Department, Medical Faculty, Ondokuz Mayıs University , Samsun , Turkey .
Gurkan
G
Genc
Ali
A
Okuyucu
Bilge Can
BC
Meydan
Oguzhan
O
Yavuz
Ozlem
O
Nisbet
Murat
M
Hokelek
Abdulkerim
A
Bedir
Ozan
O
Ozkaya
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D003401:Creatine / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015431:Weight Loss / Q000187:drug effects
D000970:Antineoplastic Agents; D003401:Creatine; D002945:Cisplatin
Cisplatin; creatine monohydrate; genotoxicity; mtDNA; nephrotoxicity