Radioprotective action of curcumin extracted from Curcuma longa LINN: inhibitory effect on formation of urinary 8-hydroxy-2'-deoxyguanosine, tumorigenesis, but not mortality, induced by gamma-ray irradiation.
OBJECTIVE
We evaluated the radioprotective action of curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] extracted from Curcuma longa LINN against the acute and chronic effects and the mortality induced by exposure to radiation using female rats.


METHODS
For the assay of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine, a marker for acute effects, Wistar-MS virgin rats were fed the basal diet with exposure at 0 or 3 Gy to gamma-rays from a 60Co source as the control. Rats in the experimental groups received whole-body irradiation with 3 Gy and were fed a diet containing 1% (wt/wt) curcumin for 3 days before and/or 2 days after irradiation. The urine was collected for a 24-h period between 1 and 2 days after irradiation. Urine samples were used to determine the 8-OHdG level using an enzyme-linked immunosorbent assay and the creatinine level by a modified Jaffé reaction. For long-term effects, rats at Day 17 of pregnancy were fed a diet containing curcumin for 3 days before and/or 3 days after irradiation with 1.5 Gy, and received a pellet of diethylstilbestrol as the promoter. The rats were examined for mammary and pituitary tumors for 1 year. To determine survival, virgin rats received whole-body irradiation with 9.6 Gy and were fed a diet containing curcumin for 3 days before and/or 3 days after irradiation. After irradiation, all rats were assessed daily for survival for 30 days.


RESULTS
Acutely in virgin rats irradiated with 3 Gy, the creatinine-corrected concentration and total amount of 8-OHdG in the 24-h urine samples were higher (approximately 1.3-fold) than the corresponding values in the nonirradiated controls. Adding curcumin to the diet for 3 days before and/or 2 days after irradiation reduced the elevated 8-OHdG levels by 50-70%. The evaluation of the protective action of curcumin against the long-term effects revealed that curcumin significantly decreased the incidence of mammary and pituitary tumors. However, the experiments on survival revealed that curcumin was not effective when administered for 3 days before and/or 3 days after irradiation (9.6 Gy).


CONCLUSIONS
These findings demonstrate that curcumin can be used as an effective radioprotective agent to inhibit acute and chronic effects, but not mortality, after irradiation.
Inano
Hiroshi
H
Redox Regulation Research Group, Research Center for Radiation Safety, National Institute of Radiological Sciences, 9-1 Anagawa-4-chome, Inage-ku, Chiba-shi 263-8555, Japan. inano@rea.or.jp
Onoda
Makoto
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002273:Carcinogens; D003404:Creatinine / Q000652:urine; D003474:Curcumin / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine*; D004054:Diethylstilbestrol; D004353:Drug Evaluation, Preclinical; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000401:mortality / Q000517:prevention & control* / Q000652:urine; D009381:Neoplasms, Radiation-Induced / Q000401:mortality / Q000517:prevention & control* / Q000652:urine; D010911:Pituitary Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000652:urine; D011247:Pregnancy; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014916:Whole-Body Irradiation / Q000401:mortality
D015415:Biomarkers; D002273:Carcinogens; D011837:Radiation-Protective Agents; D004054:Diethylstilbestrol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; D003849:Deoxyguanosine; D003474:Curcumin