title: Comparative in vivo evaluations of curcumin and its analog difluorinated curcumin against cisplatin-induced nephrotoxicity.
abstract: Curcumin, a polyphenol, has pharmacological effects including antioxidant, anti-inflammatory and anti-cancer features. In this study, we have performed comparative in vivo evaluations of CDF (curcumin difluorinated) and curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) Control; (2) Cisplatin (7 mg/kg body wt, intraperitoneal as a single dose); (3) Cisplatin and CDF (50 mg/rat/day; for 12 days); (4) Cisplatin and curcumin (50 mg/rat/day), for 12 days). Cisplatin treated rats exhibited kidney injury manifested by increased serum N-urea and creatinine (P < 0.001). Kidney from cisplatin treated rats also exhibited significant increase in malondialdehyde (MDA) and 8-isoprostane levels (P < 0.001). Treatment with CDF and curcumin prevented the rise in serum N-urea, creatinine, MDA and 8-isoprostane as compared to experimental control group in kidney (P < 0.05). Compared to curcumin, CDF had greater potential in suppressing cisplatin-induced pro-inflammatory factors NF-κB and COX-2 as well as downstream markers Nrf2 and HO-1 (P < 0.05) in kidney. The analysis on anion transport markers (OAT1 and OAT3) showed a similar trend (CDF > curcumin). CDF could reduce the expression of multi-drug resistance markers OCT1, OCT2, MRP2 and MRP4 to a much greater extent than curcumin (P < 0.05). We also demonstrate that CDF influenced the expression of p-mTOR, p-p70S6K1, p-4E-BP1 and p-Akt. These data suggest that CDF can potentially be used to reduce the chemotherapy induced nephrotoxicity thereby enhancing the therapeutic window of cisplatin. The results also proved that compared to curcumin, CDF has superior protective effect in nephrotoxicity.
authors.affiliation: Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, 23100, Turkey, nsahinkm@yahoo.com.
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
authors.forename: Cemal
authors.initials: C
authors.lastname: Orhan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Irfana
authors.initials: I
authors.lastname: Muqbil
authors.forename: Nurhan
authors.initials: N
authors.lastname: Sahin
authors.forename: Hasan
authors.initials: H
authors.lastname: Gencoglu
authors.forename: Osman
authors.initials: O
authors.lastname: Guler
authors.forename: Subhash B
authors.initials: SB
authors.lastname: Padhye
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Ramzi M
authors.initials: RM
authors.lastname: Mohammad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D003404:Creatinine; D003474:Curcumin; D006845:Hydrocarbons, Fluorinated; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins